Case Reports

The following case was encountered and treated by Capt DellaVolpe during deployment with Operation Enduring Freedom-Trans Sahara on his tour as Special Operations Flight Surgeon with the Air Force Special Operations Command. The case highlights a rare but serious disease that can be particularly challenging to manage in military members serving overseas.

Case Presentation

After 2 days of worsening dyspnea on exertion, fever, and fatigue, a previously healthy 22-year-old man presented to a remote clinic established as part of a military deployment in central Africa. Despite having received azithromycin from a field medic, his condition continued to worsen. He had no cough, recent weight changes, or night sweats. The patient’s past medical history was unremarkable, including any prior history of pulmonary disorders.

The patient was a member of the U.S. Army Military Police Corps and had been deployed for 3 weeks. His job involved local patrols, and he had no history of airborne exposures, such as mold or chemical inhalants, or travel to sandy environments. Although he was previously a nonsmoker, he reported smoking local cigarettes to help him stay awake during night patrols over the past 2 weeks. The patient’s vaccination history included influenza, tetanus, measles/mumps/rubella, yellow fever, typhoid, hepatitis A/B, anthrax, meningococcus, and smallpox, all administered before deployment. At the time of evaluation, his temperature was 103.9°F, pulse 120 bpm, respiratory rate 32 breaths per minute, and blood pressure 110/70 mm Hg. His oxygen saturation was 80% on room air.

On examination, he was in significant distress and only able to speak in short sentences. There was no jugular venous distension or stridor. He was tachycardic, with a regular rhythm, without murmurs, rubs, or gallops. A pulmonary examination revealed decreased air movement bilaterally with bilateral inspiratory crackles at the bases. There was a tactile fremitus on the right side. He had no swelling or tenderness of the extremities, and no rashes were noted.

Laboratory capabilities were limited given the remote clinic location. Rapid malaria and rapid influenza were negative. A blood smear showed no organisms. A chest X-ray showed diffuse alveolar infiltrates and homogenous opacification of the right hemithorax.

The patient was placed on continuous oxygen by facemask and started on IV ceftriaxone and vancomycin. He was volume resuscitated with normal saline, with a modest effect on his heart rate. Attempts to wean his oxygen consumption were accompanied by an immediate oxygen desaturation to the low 80s. Because of the limited supply of oxygen available at the remote location as well as the patient’s poor response to broad-spectrum antibiotic coverage over the next 8 hours, he was evacuated by airborne casualty evacuation to the critical care team at Landstuhl Regional Medical Center in Germany.

Laboratory results revealed a peripheral leukocytosis with no eosinophilia. The patient underwent bronchoalveolar lavage (BAL), which showed 30% eosinophils. A diagnosis of acute eosinophilic pneumonia (AEP) was made, and the patient was started on IV methylprednisolone. He experienced a rapid resolution of symptoms and was completely weaned off oxygen 2 days later. The following week he was released from the hospital and able to return stateside to his unit.

Discussion

This case illustrates an uncommon but potentially life-threatening cause of respiratory failure, AEP. First described as a reversible, noninfectious cause of respiratory distress, AEP is now characterized as an uncommon yet severe febrile illness, which typically presents with hypoxia, pulmonary infiltrates, and increased eosinophilia on bronchoalveolar lavage in the absence of other causes.^1-3 Untreated, AEP can progress to respiratory failure and death.

Acute eosinophilic pneumonia belongs to a heterogeneous group of disorders known as the eosinophilic lung syndromes. Although the pathophysiology has not been completely characterized, it is theorized that AEP is caused by a hypersensitivity reaction to an airborne antigen.² Interleukin-5 has been implicated in the preferential activation of eosinophils and granule release and may be responsible for the eosinophilic alveolar exudates. In addition, interleukin-5 has been established as an eosinophil chemotactant.^4-6

Acute eosinophilic pneumonia is relatively uncommon. Most epidemiologic studies have been limited to retrospective analyses and case series.⁷ However, the presentation of the disease suggests that it may be underdiagnosed.^6,8 The most common presenting signs and symptoms are dyspnea, fever, cough, and crackles on inspiration. Acute eosinophilic pneumonia has been documented in men and women of all ages with a 2:1 male predominance, typically occurring in previously healthy individuals aged 18 to 40 years.^9,10 Reports of AEP in infants also exist.¹¹

Although idiopathic cases have been described in the literature, patients, on average, will have a history of airborne toxin exposure, including smoke, sand, dust, mold, or chemicals. However, a causal relationship has not been proven.¹²

Recent initiation of smoking has been associated with AEP, as was the case with this patient. This patient had no other history of airborne exposures, including burn pits, travel to sandy environments, mold, or chemical inhalants. Of all cases of AEP described to date, more than two-thirds have been associated with smoking.^13,14 One Japanese case series further established the association through a “cigarette challenge test.”^8,15,16 Typically, the patients described were in their mid-20s and rapidly developed symptoms consistent with AEP within 1 month of initiating smoking.

A high proportion of AEP has recently been described among newly deployed military personnel in Iraq.¹⁷ Out of 180,000 personnel deployed, 18 developed AEP with 14 having initiated smoking within 1 month of deployment. The authors concluded that compared with the controls, new-onset smokers had a significantly increased risk of developing AEP. Importantly, this case series describes 2 deaths associated with this disease, suggesting that this otherwise healthy population may have other environmental exposures that put them at a higher risk than that in the general population. Another case described a U.S. soldier in Korea with recent smoking history who was diagnosed with AEP on transbronchial lung biopsy.¹⁸

Given the nonspecific symptoms of the disease, early diagnosis relies on attention to clinical history, environmental exposures, and response to initial empiric treatment. Diagnosis is made based on pulmonary eosinophilia and exclusion of chronic causes of eosinophilic pulmonary disease, such as Churg-Strauss syndrome, chronic eosinophilic pneumonia, and tropical eosinophilia.^9,19

Criteria for diagnosis has evolved since AEP was initially reported. Current criteria include acute onset febrile respiratory manifestations < 1-month duration, bilateral diffuse infiltrates on chest radiograph, arterial oxygen pressure of < 60 mm Hg or pulse oximetry < 90% on room air, and BAL > 25% eosinophils. Blood, sputum, and BAL cultures must be negative for bacteria, fungi, and parasitic causes.⁷ Exposure to toxins known to cause eosinophilia should also be ruled out. Therefore, timely BAL is of paramount importance in any suspected case of AEP. Peripheral blood count will usually show a nonspecific leukocytosis, with a normal distribution of eosinophils; however, it is not uncommon for peripheral eosinophilia to occur late in the disease.^14,20 Pulmonary eosinophilia in the absence of a peripheral eosinophilia is likely due to pulmonary eosinophil sequestration.

In one case series, the mean duration of time from symptom onset until diagnosis was 3.5 days.¹³ Diagnosis usually occurs after the patient’s clinical status worsens despite broad-spectrum antibiotic therapy. Acute eosinophilic pneumonia typically appears on a chest radiograph as bilateral reticular nodules with interstitial patterning. Variability can exist between alveolar, interstitial, and mixed infiltrate patterns.¹⁹ Pleural effusions may also be seen. These nonspecific patterns allow AEP to be easily mistaken for a variety of other pathologies, such as acute respiratory distress syndrome and community acquired pneumonia.

Corticosteroid therapy is the mainstay of treatment for AEP. Intravenous methylprednisolone is typically administered at dosages of 60 mg to 125 mg every 6 hours, followed by an oral prednisone taper.²¹ Relapses of AEP are not typical, and the prognosis is typically excellent if identified rapidly and treated appropriately. In one study of 127 individuals treated with corticosteroids, all survived, and most were transferred out of the ICU after 3 days of treatment. Dyspnea improved on treatment day 3, and all symptoms disappeared with an average of 7 days of treatment.⁷

Conclusion

Acute eosinophilic pneumonia is likely to be underreported clinically. Presently, AEP is largely a diagnosis of exclusion; the current criteria for diagnosis are fairly rigid and rely on BAL while ruling out other identifiable causes (Table). Clinical suspicion should be raised in patients with a history of new-onset smoking or other airborne toxin exposure. The broad spectrum of clinical presentations and diagnostic findings leave important questions unanswered regarding the mechanisms of the disease.

This particular case illustrates the fundamental importance of taking a thorough history in any patient with a recent airborne exposure where AEP is suspected. Acute eosinophilic pneumonia should be considered in cases of pneumonia that continue to worsen despite the treatment of IV antibiotics; a BAL should be performed when appropriate.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

The following case was encountered and treated by Capt DellaVolpe during deployment with Operation Enduring Freedom-Trans Sahara on his tour as Special Operations Flight Surgeon with the Air Force Special Operations Command. The case highlights a rare but serious disease that can be particularly challenging to manage in military members serving overseas.

Case Presentation

After 2 days of worsening dyspnea on exertion, fever, and fatigue, a previously healthy 22-year-old man presented to a remote clinic established as part of a military deployment in central Africa. Despite having received azithromycin from a field medic, his condition continued to worsen. He had no cough, recent weight changes, or night sweats. The patient’s past medical history was unremarkable, including any prior history of pulmonary disorders.

The patient was a member of the U.S. Army Military Police Corps and had been deployed for 3 weeks. His job involved local patrols, and he had no history of airborne exposures, such as mold or chemical inhalants, or travel to sandy environments. Although he was previously a nonsmoker, he reported smoking local cigarettes to help him stay awake during night patrols over the past 2 weeks. The patient’s vaccination history included influenza, tetanus, measles/mumps/rubella, yellow fever, typhoid, hepatitis A/B, anthrax, meningococcus, and smallpox, all administered before deployment. At the time of evaluation, his temperature was 103.9°F, pulse 120 bpm, respiratory rate 32 breaths per minute, and blood pressure 110/70 mm Hg. His oxygen saturation was 80% on room air.

On examination, he was in significant distress and only able to speak in short sentences. There was no jugular venous distension or stridor. He was tachycardic, with a regular rhythm, without murmurs, rubs, or gallops. A pulmonary examination revealed decreased air movement bilaterally with bilateral inspiratory crackles at the bases. There was a tactile fremitus on the right side. He had no swelling or tenderness of the extremities, and no rashes were noted.

Laboratory capabilities were limited given the remote clinic location. Rapid malaria and rapid influenza were negative. A blood smear showed no organisms. A chest X-ray showed diffuse alveolar infiltrates and homogenous opacification of the right hemithorax.

The patient was placed on continuous oxygen by facemask and started on IV ceftriaxone and vancomycin. He was volume resuscitated with normal saline, with a modest effect on his heart rate. Attempts to wean his oxygen consumption were accompanied by an immediate oxygen desaturation to the low 80s. Because of the limited supply of oxygen available at the remote location as well as the patient’s poor response to broad-spectrum antibiotic coverage over the next 8 hours, he was evacuated by airborne casualty evacuation to the critical care team at Landstuhl Regional Medical Center in Germany.

Laboratory results revealed a peripheral leukocytosis with no eosinophilia. The patient underwent bronchoalveolar lavage (BAL), which showed 30% eosinophils. A diagnosis of acute eosinophilic pneumonia (AEP) was made, and the patient was started on IV methylprednisolone. He experienced a rapid resolution of symptoms and was completely weaned off oxygen 2 days later. The following week he was released from the hospital and able to return stateside to his unit.

Discussion

This case illustrates an uncommon but potentially life-threatening cause of respiratory failure, AEP. First described as a reversible, noninfectious cause of respiratory distress, AEP is now characterized as an uncommon yet severe febrile illness, which typically presents with hypoxia, pulmonary infiltrates, and increased eosinophilia on bronchoalveolar lavage in the absence of other causes.^1-3 Untreated, AEP can progress to respiratory failure and death.

Acute eosinophilic pneumonia belongs to a heterogeneous group of disorders known as the eosinophilic lung syndromes. Although the pathophysiology has not been completely characterized, it is theorized that AEP is caused by a hypersensitivity reaction to an airborne antigen.² Interleukin-5 has been implicated in the preferential activation of eosinophils and granule release and may be responsible for the eosinophilic alveolar exudates. In addition, interleukin-5 has been established as an eosinophil chemotactant.^4-6

Acute eosinophilic pneumonia is relatively uncommon. Most epidemiologic studies have been limited to retrospective analyses and case series.⁷ However, the presentation of the disease suggests that it may be underdiagnosed.^6,8 The most common presenting signs and symptoms are dyspnea, fever, cough, and crackles on inspiration. Acute eosinophilic pneumonia has been documented in men and women of all ages with a 2:1 male predominance, typically occurring in previously healthy individuals aged 18 to 40 years.^9,10 Reports of AEP in infants also exist.¹¹

Although idiopathic cases have been described in the literature, patients, on average, will have a history of airborne toxin exposure, including smoke, sand, dust, mold, or chemicals. However, a causal relationship has not been proven.¹²

Recent initiation of smoking has been associated with AEP, as was the case with this patient. This patient had no other history of airborne exposures, including burn pits, travel to sandy environments, mold, or chemical inhalants. Of all cases of AEP described to date, more than two-thirds have been associated with smoking.^13,14 One Japanese case series further established the association through a “cigarette challenge test.”^8,15,16 Typically, the patients described were in their mid-20s and rapidly developed symptoms consistent with AEP within 1 month of initiating smoking.

A high proportion of AEP has recently been described among newly deployed military personnel in Iraq.¹⁷ Out of 180,000 personnel deployed, 18 developed AEP with 14 having initiated smoking within 1 month of deployment. The authors concluded that compared with the controls, new-onset smokers had a significantly increased risk of developing AEP. Importantly, this case series describes 2 deaths associated with this disease, suggesting that this otherwise healthy population may have other environmental exposures that put them at a higher risk than that in the general population. Another case described a U.S. soldier in Korea with recent smoking history who was diagnosed with AEP on transbronchial lung biopsy.¹⁸

Given the nonspecific symptoms of the disease, early diagnosis relies on attention to clinical history, environmental exposures, and response to initial empiric treatment. Diagnosis is made based on pulmonary eosinophilia and exclusion of chronic causes of eosinophilic pulmonary disease, such as Churg-Strauss syndrome, chronic eosinophilic pneumonia, and tropical eosinophilia.^9,19

Criteria for diagnosis has evolved since AEP was initially reported. Current criteria include acute onset febrile respiratory manifestations < 1-month duration, bilateral diffuse infiltrates on chest radiograph, arterial oxygen pressure of < 60 mm Hg or pulse oximetry < 90% on room air, and BAL > 25% eosinophils. Blood, sputum, and BAL cultures must be negative for bacteria, fungi, and parasitic causes.⁷ Exposure to toxins known to cause eosinophilia should also be ruled out. Therefore, timely BAL is of paramount importance in any suspected case of AEP. Peripheral blood count will usually show a nonspecific leukocytosis, with a normal distribution of eosinophils; however, it is not uncommon for peripheral eosinophilia to occur late in the disease.^14,20 Pulmonary eosinophilia in the absence of a peripheral eosinophilia is likely due to pulmonary eosinophil sequestration.

In one case series, the mean duration of time from symptom onset until diagnosis was 3.5 days.¹³ Diagnosis usually occurs after the patient’s clinical status worsens despite broad-spectrum antibiotic therapy. Acute eosinophilic pneumonia typically appears on a chest radiograph as bilateral reticular nodules with interstitial patterning. Variability can exist between alveolar, interstitial, and mixed infiltrate patterns.¹⁹ Pleural effusions may also be seen. These nonspecific patterns allow AEP to be easily mistaken for a variety of other pathologies, such as acute respiratory distress syndrome and community acquired pneumonia.

Corticosteroid therapy is the mainstay of treatment for AEP. Intravenous methylprednisolone is typically administered at dosages of 60 mg to 125 mg every 6 hours, followed by an oral prednisone taper.²¹ Relapses of AEP are not typical, and the prognosis is typically excellent if identified rapidly and treated appropriately. In one study of 127 individuals treated with corticosteroids, all survived, and most were transferred out of the ICU after 3 days of treatment. Dyspnea improved on treatment day 3, and all symptoms disappeared with an average of 7 days of treatment.⁷

Conclusion

Acute eosinophilic pneumonia is likely to be underreported clinically. Presently, AEP is largely a diagnosis of exclusion; the current criteria for diagnosis are fairly rigid and rely on BAL while ruling out other identifiable causes (Table). Clinical suspicion should be raised in patients with a history of new-onset smoking or other airborne toxin exposure. The broad spectrum of clinical presentations and diagnostic findings leave important questions unanswered regarding the mechanisms of the disease.

This particular case illustrates the fundamental importance of taking a thorough history in any patient with a recent airborne exposure where AEP is suspected. Acute eosinophilic pneumonia should be considered in cases of pneumonia that continue to worsen despite the treatment of IV antibiotics; a BAL should be performed when appropriate.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

The following case was encountered and treated by Capt DellaVolpe during deployment with Operation Enduring Freedom-Trans Sahara on his tour as Special Operations Flight Surgeon with the Air Force Special Operations Command. The case highlights a rare but serious disease that can be particularly challenging to manage in military members serving overseas.

Case Presentation

After 2 days of worsening dyspnea on exertion, fever, and fatigue, a previously healthy 22-year-old man presented to a remote clinic established as part of a military deployment in central Africa. Despite having received azithromycin from a field medic, his condition continued to worsen. He had no cough, recent weight changes, or night sweats. The patient’s past medical history was unremarkable, including any prior history of pulmonary disorders.

The patient was a member of the U.S. Army Military Police Corps and had been deployed for 3 weeks. His job involved local patrols, and he had no history of airborne exposures, such as mold or chemical inhalants, or travel to sandy environments. Although he was previously a nonsmoker, he reported smoking local cigarettes to help him stay awake during night patrols over the past 2 weeks. The patient’s vaccination history included influenza, tetanus, measles/mumps/rubella, yellow fever, typhoid, hepatitis A/B, anthrax, meningococcus, and smallpox, all administered before deployment. At the time of evaluation, his temperature was 103.9°F, pulse 120 bpm, respiratory rate 32 breaths per minute, and blood pressure 110/70 mm Hg. His oxygen saturation was 80% on room air.

On examination, he was in significant distress and only able to speak in short sentences. There was no jugular venous distension or stridor. He was tachycardic, with a regular rhythm, without murmurs, rubs, or gallops. A pulmonary examination revealed decreased air movement bilaterally with bilateral inspiratory crackles at the bases. There was a tactile fremitus on the right side. He had no swelling or tenderness of the extremities, and no rashes were noted.

Laboratory capabilities were limited given the remote clinic location. Rapid malaria and rapid influenza were negative. A blood smear showed no organisms. A chest X-ray showed diffuse alveolar infiltrates and homogenous opacification of the right hemithorax.

The patient was placed on continuous oxygen by facemask and started on IV ceftriaxone and vancomycin. He was volume resuscitated with normal saline, with a modest effect on his heart rate. Attempts to wean his oxygen consumption were accompanied by an immediate oxygen desaturation to the low 80s. Because of the limited supply of oxygen available at the remote location as well as the patient’s poor response to broad-spectrum antibiotic coverage over the next 8 hours, he was evacuated by airborne casualty evacuation to the critical care team at Landstuhl Regional Medical Center in Germany.

Laboratory results revealed a peripheral leukocytosis with no eosinophilia. The patient underwent bronchoalveolar lavage (BAL), which showed 30% eosinophils. A diagnosis of acute eosinophilic pneumonia (AEP) was made, and the patient was started on IV methylprednisolone. He experienced a rapid resolution of symptoms and was completely weaned off oxygen 2 days later. The following week he was released from the hospital and able to return stateside to his unit.

Discussion

This case illustrates an uncommon but potentially life-threatening cause of respiratory failure, AEP. First described as a reversible, noninfectious cause of respiratory distress, AEP is now characterized as an uncommon yet severe febrile illness, which typically presents with hypoxia, pulmonary infiltrates, and increased eosinophilia on bronchoalveolar lavage in the absence of other causes.^1-3 Untreated, AEP can progress to respiratory failure and death.

Acute eosinophilic pneumonia belongs to a heterogeneous group of disorders known as the eosinophilic lung syndromes. Although the pathophysiology has not been completely characterized, it is theorized that AEP is caused by a hypersensitivity reaction to an airborne antigen.² Interleukin-5 has been implicated in the preferential activation of eosinophils and granule release and may be responsible for the eosinophilic alveolar exudates. In addition, interleukin-5 has been established as an eosinophil chemotactant.^4-6

Acute eosinophilic pneumonia is relatively uncommon. Most epidemiologic studies have been limited to retrospective analyses and case series.⁷ However, the presentation of the disease suggests that it may be underdiagnosed.^6,8 The most common presenting signs and symptoms are dyspnea, fever, cough, and crackles on inspiration. Acute eosinophilic pneumonia has been documented in men and women of all ages with a 2:1 male predominance, typically occurring in previously healthy individuals aged 18 to 40 years.^9,10 Reports of AEP in infants also exist.¹¹

Although idiopathic cases have been described in the literature, patients, on average, will have a history of airborne toxin exposure, including smoke, sand, dust, mold, or chemicals. However, a causal relationship has not been proven.¹²

Recent initiation of smoking has been associated with AEP, as was the case with this patient. This patient had no other history of airborne exposures, including burn pits, travel to sandy environments, mold, or chemical inhalants. Of all cases of AEP described to date, more than two-thirds have been associated with smoking.^13,14 One Japanese case series further established the association through a “cigarette challenge test.”^8,15,16 Typically, the patients described were in their mid-20s and rapidly developed symptoms consistent with AEP within 1 month of initiating smoking.

A high proportion of AEP has recently been described among newly deployed military personnel in Iraq.¹⁷ Out of 180,000 personnel deployed, 18 developed AEP with 14 having initiated smoking within 1 month of deployment. The authors concluded that compared with the controls, new-onset smokers had a significantly increased risk of developing AEP. Importantly, this case series describes 2 deaths associated with this disease, suggesting that this otherwise healthy population may have other environmental exposures that put them at a higher risk than that in the general population. Another case described a U.S. soldier in Korea with recent smoking history who was diagnosed with AEP on transbronchial lung biopsy.¹⁸

Given the nonspecific symptoms of the disease, early diagnosis relies on attention to clinical history, environmental exposures, and response to initial empiric treatment. Diagnosis is made based on pulmonary eosinophilia and exclusion of chronic causes of eosinophilic pulmonary disease, such as Churg-Strauss syndrome, chronic eosinophilic pneumonia, and tropical eosinophilia.^9,19

Criteria for diagnosis has evolved since AEP was initially reported. Current criteria include acute onset febrile respiratory manifestations < 1-month duration, bilateral diffuse infiltrates on chest radiograph, arterial oxygen pressure of < 60 mm Hg or pulse oximetry < 90% on room air, and BAL > 25% eosinophils. Blood, sputum, and BAL cultures must be negative for bacteria, fungi, and parasitic causes.⁷ Exposure to toxins known to cause eosinophilia should also be ruled out. Therefore, timely BAL is of paramount importance in any suspected case of AEP. Peripheral blood count will usually show a nonspecific leukocytosis, with a normal distribution of eosinophils; however, it is not uncommon for peripheral eosinophilia to occur late in the disease.^14,20 Pulmonary eosinophilia in the absence of a peripheral eosinophilia is likely due to pulmonary eosinophil sequestration.

In one case series, the mean duration of time from symptom onset until diagnosis was 3.5 days.¹³ Diagnosis usually occurs after the patient’s clinical status worsens despite broad-spectrum antibiotic therapy. Acute eosinophilic pneumonia typically appears on a chest radiograph as bilateral reticular nodules with interstitial patterning. Variability can exist between alveolar, interstitial, and mixed infiltrate patterns.¹⁹ Pleural effusions may also be seen. These nonspecific patterns allow AEP to be easily mistaken for a variety of other pathologies, such as acute respiratory distress syndrome and community acquired pneumonia.

Corticosteroid therapy is the mainstay of treatment for AEP. Intravenous methylprednisolone is typically administered at dosages of 60 mg to 125 mg every 6 hours, followed by an oral prednisone taper.²¹ Relapses of AEP are not typical, and the prognosis is typically excellent if identified rapidly and treated appropriately. In one study of 127 individuals treated with corticosteroids, all survived, and most were transferred out of the ICU after 3 days of treatment. Dyspnea improved on treatment day 3, and all symptoms disappeared with an average of 7 days of treatment.⁷

Conclusion

Acute eosinophilic pneumonia is likely to be underreported clinically. Presently, AEP is largely a diagnosis of exclusion; the current criteria for diagnosis are fairly rigid and rely on BAL while ruling out other identifiable causes (Table). Clinical suspicion should be raised in patients with a history of new-onset smoking or other airborne toxin exposure. The broad spectrum of clinical presentations and diagnostic findings leave important questions unanswered regarding the mechanisms of the disease.

This particular case illustrates the fundamental importance of taking a thorough history in any patient with a recent airborne exposure where AEP is suspected. Acute eosinophilic pneumonia should be considered in cases of pneumonia that continue to worsen despite the treatment of IV antibiotics; a BAL should be performed when appropriate.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Left ventricular noncompaction (LVNC) is a rare disorder that is variably classified as a primary genetic cardiomyopathy (CM) by the American Heart Association.¹ It is mostly believed to be a congenital abnormality, characterized by the arrest of the typical embryonic myocardial maturation process with the subsequent retention of the trabecular myocardial structure, which defines the early embryonic heart.²

During very early embryonic development, the left ventricular (LV)myocardium is composed of a loose network of fibers separated by deep recesses, which link it with the LV cavity. At 8 weeks of prenatal development, gradual compaction of these fibers occurs, and LVNC is thought to result from the arrest of this normal process.^2,3 Significant variability in myocardial involvement exists, ranging from panventricular to isolated apical involvement, likely related to time of arrest of this maturation process.⁴ The decreased contractile capability and inadequate epicardial coronary system communication of this trabecular endocardium is thought to lead to the clinical manifestations of LVNC.^1-7

This report describes the case of a 45-year-old male soldier who presented with a unique case of heart failure, diagnosed via cardiac magnetic resonance imaging (MRI).

Case Study

The patient presented to the San Antonio Military Medical Center emergency department in mid-2011 with increasing dyspnea for several weeks. He also reported significant lower-extremity and scrotal edema. Although the patient had been previously healthy, his recent medical history was remarkable for a severe combat injury suffered while on duty with the U.S. Army in Afghanistan: He was involved in an explosion from an improvised explosive device in August 2009. He was medically evacuated to the U.S., where he required multiple hospitalizations and surgeries. Prior to his current presentation, the patient had been briefly hospitalized for hospital-acquired pneumonia. During this hospitalization, he first noted abnormal swelling of his legs, a finding that was initially attributed to the large sodium load he had received with his IV antibiotics.

DIAGNOSIS

The patient’s vital signs on presentation were notable for 100/83 mm Hg blood pressure, 103 beats per minute (bpm) heart rate, and 18/min respiratory rate with a saturation of 100% on 4 liters of oxygen by nasal cannula. He was conversant but tachypneic and had to pause frequently to catch his breath. His neck veins were notably distended with jugular venous pulsations visible to the angle of the jaw with the patient at 30 degrees. His heart sounds were normal without an S3, but his lungs were notable for bilateral crackles over the lower- to mid-lung fields. He had profound bilateral upper and lower extremity and scrotal pitting edema. He had no lymphadenopathy or skin rashes.

On presentation, the patient’s laboratory results were remarkable for a 444 pg/mL brain natriuretic peptide. A chest X-ray revealed bilateral basilar opacities. An electrocardiogram showed normal sinus rhythm  (70 bpm), with normal axis and poor R-wave progression across the precordium. An echocardiogram was performed and notable for a moderately dilated left ventricle with severely depressed systolic function of 10% to 15%, and elevated pulmonary artery pressures. Subsequently, the patient was referred for a coronary angiography, which showed no evidence of coronary atherosclerosis. A cardiac MRI was then performed to evaluate for nonischemic CM, which revealed prominent trabeculations in both ventricles, but most notably in the left ventricle, consistent with a diagnosis of LVNC.

The patient was treated with diuretics, beta-blockers, and an angiotensin-converting enzyme (ACE) inhibitor with improvement in his heart failure symptoms. He was started on systemic anticoagulation with warfarin for his severely depressed LV function. His hospital course was complicated by frequent, nonsustained ventricular tachycardia (VT), and he was referred to the electrophysiology service for implantation of an automated intracardiac cardioverter/defibrillator (AICD) for primary prevention of sudden cardiac death. His clinical course was otherwise unremarkable, and he was discharged after 8 days with complete resolution of his symptoms.

Discussion

The clinical presentation of LVNC is typically due to complications of ventricular dysfunction, including heart failure, arrhythmias, and cardioembolic events. Retrospective studies have shown much variability in the frequency of these complications, likely due to selection bias in earlier studies. These earlier studies had suggested a frequency of heart failure > 50%, but recent studies have shown a more modest frequency of 30% to 35% of affected patients.

Even greater variance has been found in the frequency of arrhythmias, but most studies have shown a frequency of at least 20% for VT. Poor blood flow in the deep intertrabecular recesses in patients with LVNC is additionally thought to lead to a predisposition for mural thrombus formation with an elevated frequency of systemic embolic events, ranging from 5% to 20% among previous studies.^1-4,6,8

Much debate remains regarding the genetic association of this condition. The unique character of the resulting myocardium suggests a distinct CM, but the significant genetic heterogeneity with sarcomere protein gene mutations associated with several other CMs, including hypertrophic and dilated CM, suggests that LVNC may simply exist on a phenotypic continuum with these other conditions.⁴ Inheritance shows additional similarities to these other known CMs with autosomal-
dominant and X-linked modes of transmission shown with familial forms in about 25% of patients.^5,7 This has led many to believe that screening of first-degree relatives of clinically affected patients may be appropriate.

The prevalence of LVNC in adults referred for echocardiography is about 0.014% to 1.3%.⁵ A recent increase in the rate of recognition has raised concerns of possible overdiagnosis, with attempts now made to develop specific imaging diagnostic criteria. Diagnosis of LVNC is most commonly suspected (but can be missed) on echocardiography using 2-D and color Doppler imaging modalities. Echocardiographic findings supporting the diagnosis of LVNC suggested by Oechslin and colleague include:

• Presence of multiple trabeculations, particularly in the LV apex and free wall;

• Multiple deep trabeculation recesses in communication with the LV cavity, usually seen on color Doppler imaging;

• A 2-layered structure of the endomyocardium with ratio of end systolic, noncompacted endocardial layer to compacted epicardial layer > 2 in adults; and

• Absence of other congenital or acquired heart disease, particularly those causing LV outflow obstruction.⁸

Another proposed standardized method for identifying LVNC via echocardiography by Chin and colleagues focuses on trabeculae at the LV apex on the parasternal short axis and apical views.^2,3 LVNC is defined by a ratio of X/Y of ≤ 0.5, where X is the distance from the epicardial surface to the trough of the trabecular recess, and Y is the distance from the epicardial surface to the peak of the trabeculations.

Cardiac MRI is now a more common mode of imaging used for diagnosis of LVNC and often has better imaging characteristics than those of echocardiography. Using a ratio of noncompacted to compacted CM in diastole > 2.3 is suggestive of LVNC with sensitivity and specificity of 86% and 99%.⁹

The management of LVNC focuses primarily on treatment of complications, including heart failure, rhythm disturbances, and thromboembolic events. Treatment of heart failure is typically the same as for other CMs and includes medical therapy with salt restriction, diuretics, beta-blockers, and ACE inhibitors. In addition, exercise training, as tolerated, is beneficial to improve clinical status.^3,10 Electrophysiology studies are often performed in these patients, and implantation of an AICD is typically done in cases of documented, sustained VT, presyncope with inducible VT or severally depressed ejection fraction of < 35%.^4,10 Deep intertrabecular recesses and impaired blood flow increase the risk of thrombus formation. Hence, anticoagulation with warfarin (international normalized ratio target 2.3) for those with an impaired LV ejection fraction (< 40%) should be considered for the prevention of cardioembolic events.^3,4,6,10

Summary

An active-duty solider with a history of battlefield trauma and multiple hospitalizations was admitted for symptomatic heart failure with cardiac MRI suggestive of LVNC. This condition is a phenotypic result of genetic heterogeneity with significant variability in clinical presentation and a predisposition for heart failure, ventricular arrhythmias, and systemic embolic events. The etiology of this patient’s clinical presentation remains unclear, and additional research is needed to understand whether his recent trauma and multiple hospitalizations played a role in the manifestation of his disease.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Left ventricular noncompaction (LVNC) is a rare disorder that is variably classified as a primary genetic cardiomyopathy (CM) by the American Heart Association.¹ It is mostly believed to be a congenital abnormality, characterized by the arrest of the typical embryonic myocardial maturation process with the subsequent retention of the trabecular myocardial structure, which defines the early embryonic heart.²

During very early embryonic development, the left ventricular (LV)myocardium is composed of a loose network of fibers separated by deep recesses, which link it with the LV cavity. At 8 weeks of prenatal development, gradual compaction of these fibers occurs, and LVNC is thought to result from the arrest of this normal process.^2,3 Significant variability in myocardial involvement exists, ranging from panventricular to isolated apical involvement, likely related to time of arrest of this maturation process.⁴ The decreased contractile capability and inadequate epicardial coronary system communication of this trabecular endocardium is thought to lead to the clinical manifestations of LVNC.^1-7

This report describes the case of a 45-year-old male soldier who presented with a unique case of heart failure, diagnosed via cardiac magnetic resonance imaging (MRI).

Case Study

The patient presented to the San Antonio Military Medical Center emergency department in mid-2011 with increasing dyspnea for several weeks. He also reported significant lower-extremity and scrotal edema. Although the patient had been previously healthy, his recent medical history was remarkable for a severe combat injury suffered while on duty with the U.S. Army in Afghanistan: He was involved in an explosion from an improvised explosive device in August 2009. He was medically evacuated to the U.S., where he required multiple hospitalizations and surgeries. Prior to his current presentation, the patient had been briefly hospitalized for hospital-acquired pneumonia. During this hospitalization, he first noted abnormal swelling of his legs, a finding that was initially attributed to the large sodium load he had received with his IV antibiotics.

DIAGNOSIS

The patient’s vital signs on presentation were notable for 100/83 mm Hg blood pressure, 103 beats per minute (bpm) heart rate, and 18/min respiratory rate with a saturation of 100% on 4 liters of oxygen by nasal cannula. He was conversant but tachypneic and had to pause frequently to catch his breath. His neck veins were notably distended with jugular venous pulsations visible to the angle of the jaw with the patient at 30 degrees. His heart sounds were normal without an S3, but his lungs were notable for bilateral crackles over the lower- to mid-lung fields. He had profound bilateral upper and lower extremity and scrotal pitting edema. He had no lymphadenopathy or skin rashes.

On presentation, the patient’s laboratory results were remarkable for a 444 pg/mL brain natriuretic peptide. A chest X-ray revealed bilateral basilar opacities. An electrocardiogram showed normal sinus rhythm  (70 bpm), with normal axis and poor R-wave progression across the precordium. An echocardiogram was performed and notable for a moderately dilated left ventricle with severely depressed systolic function of 10% to 15%, and elevated pulmonary artery pressures. Subsequently, the patient was referred for a coronary angiography, which showed no evidence of coronary atherosclerosis. A cardiac MRI was then performed to evaluate for nonischemic CM, which revealed prominent trabeculations in both ventricles, but most notably in the left ventricle, consistent with a diagnosis of LVNC.

The patient was treated with diuretics, beta-blockers, and an angiotensin-converting enzyme (ACE) inhibitor with improvement in his heart failure symptoms. He was started on systemic anticoagulation with warfarin for his severely depressed LV function. His hospital course was complicated by frequent, nonsustained ventricular tachycardia (VT), and he was referred to the electrophysiology service for implantation of an automated intracardiac cardioverter/defibrillator (AICD) for primary prevention of sudden cardiac death. His clinical course was otherwise unremarkable, and he was discharged after 8 days with complete resolution of his symptoms.

Discussion

The clinical presentation of LVNC is typically due to complications of ventricular dysfunction, including heart failure, arrhythmias, and cardioembolic events. Retrospective studies have shown much variability in the frequency of these complications, likely due to selection bias in earlier studies. These earlier studies had suggested a frequency of heart failure > 50%, but recent studies have shown a more modest frequency of 30% to 35% of affected patients.

Even greater variance has been found in the frequency of arrhythmias, but most studies have shown a frequency of at least 20% for VT. Poor blood flow in the deep intertrabecular recesses in patients with LVNC is additionally thought to lead to a predisposition for mural thrombus formation with an elevated frequency of systemic embolic events, ranging from 5% to 20% among previous studies.^1-4,6,8

Much debate remains regarding the genetic association of this condition. The unique character of the resulting myocardium suggests a distinct CM, but the significant genetic heterogeneity with sarcomere protein gene mutations associated with several other CMs, including hypertrophic and dilated CM, suggests that LVNC may simply exist on a phenotypic continuum with these other conditions.⁴ Inheritance shows additional similarities to these other known CMs with autosomal-
dominant and X-linked modes of transmission shown with familial forms in about 25% of patients.^5,7 This has led many to believe that screening of first-degree relatives of clinically affected patients may be appropriate.

The prevalence of LVNC in adults referred for echocardiography is about 0.014% to 1.3%.⁵ A recent increase in the rate of recognition has raised concerns of possible overdiagnosis, with attempts now made to develop specific imaging diagnostic criteria. Diagnosis of LVNC is most commonly suspected (but can be missed) on echocardiography using 2-D and color Doppler imaging modalities. Echocardiographic findings supporting the diagnosis of LVNC suggested by Oechslin and colleague include:

• Presence of multiple trabeculations, particularly in the LV apex and free wall;

• Multiple deep trabeculation recesses in communication with the LV cavity, usually seen on color Doppler imaging;

• A 2-layered structure of the endomyocardium with ratio of end systolic, noncompacted endocardial layer to compacted epicardial layer > 2 in adults; and

• Absence of other congenital or acquired heart disease, particularly those causing LV outflow obstruction.⁸

Another proposed standardized method for identifying LVNC via echocardiography by Chin and colleagues focuses on trabeculae at the LV apex on the parasternal short axis and apical views.^2,3 LVNC is defined by a ratio of X/Y of ≤ 0.5, where X is the distance from the epicardial surface to the trough of the trabecular recess, and Y is the distance from the epicardial surface to the peak of the trabeculations.

Cardiac MRI is now a more common mode of imaging used for diagnosis of LVNC and often has better imaging characteristics than those of echocardiography. Using a ratio of noncompacted to compacted CM in diastole > 2.3 is suggestive of LVNC with sensitivity and specificity of 86% and 99%.⁹

The management of LVNC focuses primarily on treatment of complications, including heart failure, rhythm disturbances, and thromboembolic events. Treatment of heart failure is typically the same as for other CMs and includes medical therapy with salt restriction, diuretics, beta-blockers, and ACE inhibitors. In addition, exercise training, as tolerated, is beneficial to improve clinical status.^3,10 Electrophysiology studies are often performed in these patients, and implantation of an AICD is typically done in cases of documented, sustained VT, presyncope with inducible VT or severally depressed ejection fraction of < 35%.^4,10 Deep intertrabecular recesses and impaired blood flow increase the risk of thrombus formation. Hence, anticoagulation with warfarin (international normalized ratio target 2.3) for those with an impaired LV ejection fraction (< 40%) should be considered for the prevention of cardioembolic events.^3,4,6,10

Summary

An active-duty solider with a history of battlefield trauma and multiple hospitalizations was admitted for symptomatic heart failure with cardiac MRI suggestive of LVNC. This condition is a phenotypic result of genetic heterogeneity with significant variability in clinical presentation and a predisposition for heart failure, ventricular arrhythmias, and systemic embolic events. The etiology of this patient’s clinical presentation remains unclear, and additional research is needed to understand whether his recent trauma and multiple hospitalizations played a role in the manifestation of his disease.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Left ventricular noncompaction (LVNC) is a rare disorder that is variably classified as a primary genetic cardiomyopathy (CM) by the American Heart Association.¹ It is mostly believed to be a congenital abnormality, characterized by the arrest of the typical embryonic myocardial maturation process with the subsequent retention of the trabecular myocardial structure, which defines the early embryonic heart.²

During very early embryonic development, the left ventricular (LV)myocardium is composed of a loose network of fibers separated by deep recesses, which link it with the LV cavity. At 8 weeks of prenatal development, gradual compaction of these fibers occurs, and LVNC is thought to result from the arrest of this normal process.^2,3 Significant variability in myocardial involvement exists, ranging from panventricular to isolated apical involvement, likely related to time of arrest of this maturation process.⁴ The decreased contractile capability and inadequate epicardial coronary system communication of this trabecular endocardium is thought to lead to the clinical manifestations of LVNC.^1-7

This report describes the case of a 45-year-old male soldier who presented with a unique case of heart failure, diagnosed via cardiac magnetic resonance imaging (MRI).

Case Study

The patient presented to the San Antonio Military Medical Center emergency department in mid-2011 with increasing dyspnea for several weeks. He also reported significant lower-extremity and scrotal edema. Although the patient had been previously healthy, his recent medical history was remarkable for a severe combat injury suffered while on duty with the U.S. Army in Afghanistan: He was involved in an explosion from an improvised explosive device in August 2009. He was medically evacuated to the U.S., where he required multiple hospitalizations and surgeries. Prior to his current presentation, the patient had been briefly hospitalized for hospital-acquired pneumonia. During this hospitalization, he first noted abnormal swelling of his legs, a finding that was initially attributed to the large sodium load he had received with his IV antibiotics.

DIAGNOSIS

The patient’s vital signs on presentation were notable for 100/83 mm Hg blood pressure, 103 beats per minute (bpm) heart rate, and 18/min respiratory rate with a saturation of 100% on 4 liters of oxygen by nasal cannula. He was conversant but tachypneic and had to pause frequently to catch his breath. His neck veins were notably distended with jugular venous pulsations visible to the angle of the jaw with the patient at 30 degrees. His heart sounds were normal without an S3, but his lungs were notable for bilateral crackles over the lower- to mid-lung fields. He had profound bilateral upper and lower extremity and scrotal pitting edema. He had no lymphadenopathy or skin rashes.

On presentation, the patient’s laboratory results were remarkable for a 444 pg/mL brain natriuretic peptide. A chest X-ray revealed bilateral basilar opacities. An electrocardiogram showed normal sinus rhythm  (70 bpm), with normal axis and poor R-wave progression across the precordium. An echocardiogram was performed and notable for a moderately dilated left ventricle with severely depressed systolic function of 10% to 15%, and elevated pulmonary artery pressures. Subsequently, the patient was referred for a coronary angiography, which showed no evidence of coronary atherosclerosis. A cardiac MRI was then performed to evaluate for nonischemic CM, which revealed prominent trabeculations in both ventricles, but most notably in the left ventricle, consistent with a diagnosis of LVNC.

The patient was treated with diuretics, beta-blockers, and an angiotensin-converting enzyme (ACE) inhibitor with improvement in his heart failure symptoms. He was started on systemic anticoagulation with warfarin for his severely depressed LV function. His hospital course was complicated by frequent, nonsustained ventricular tachycardia (VT), and he was referred to the electrophysiology service for implantation of an automated intracardiac cardioverter/defibrillator (AICD) for primary prevention of sudden cardiac death. His clinical course was otherwise unremarkable, and he was discharged after 8 days with complete resolution of his symptoms.

Discussion

The clinical presentation of LVNC is typically due to complications of ventricular dysfunction, including heart failure, arrhythmias, and cardioembolic events. Retrospective studies have shown much variability in the frequency of these complications, likely due to selection bias in earlier studies. These earlier studies had suggested a frequency of heart failure > 50%, but recent studies have shown a more modest frequency of 30% to 35% of affected patients.

Even greater variance has been found in the frequency of arrhythmias, but most studies have shown a frequency of at least 20% for VT. Poor blood flow in the deep intertrabecular recesses in patients with LVNC is additionally thought to lead to a predisposition for mural thrombus formation with an elevated frequency of systemic embolic events, ranging from 5% to 20% among previous studies.^1-4,6,8

Much debate remains regarding the genetic association of this condition. The unique character of the resulting myocardium suggests a distinct CM, but the significant genetic heterogeneity with sarcomere protein gene mutations associated with several other CMs, including hypertrophic and dilated CM, suggests that LVNC may simply exist on a phenotypic continuum with these other conditions.⁴ Inheritance shows additional similarities to these other known CMs with autosomal-
dominant and X-linked modes of transmission shown with familial forms in about 25% of patients.^5,7 This has led many to believe that screening of first-degree relatives of clinically affected patients may be appropriate.

The prevalence of LVNC in adults referred for echocardiography is about 0.014% to 1.3%.⁵ A recent increase in the rate of recognition has raised concerns of possible overdiagnosis, with attempts now made to develop specific imaging diagnostic criteria. Diagnosis of LVNC is most commonly suspected (but can be missed) on echocardiography using 2-D and color Doppler imaging modalities. Echocardiographic findings supporting the diagnosis of LVNC suggested by Oechslin and colleague include:

• Presence of multiple trabeculations, particularly in the LV apex and free wall;

• Multiple deep trabeculation recesses in communication with the LV cavity, usually seen on color Doppler imaging;

• A 2-layered structure of the endomyocardium with ratio of end systolic, noncompacted endocardial layer to compacted epicardial layer > 2 in adults; and

• Absence of other congenital or acquired heart disease, particularly those causing LV outflow obstruction.⁸

Another proposed standardized method for identifying LVNC via echocardiography by Chin and colleagues focuses on trabeculae at the LV apex on the parasternal short axis and apical views.^2,3 LVNC is defined by a ratio of X/Y of ≤ 0.5, where X is the distance from the epicardial surface to the trough of the trabecular recess, and Y is the distance from the epicardial surface to the peak of the trabeculations.

Cardiac MRI is now a more common mode of imaging used for diagnosis of LVNC and often has better imaging characteristics than those of echocardiography. Using a ratio of noncompacted to compacted CM in diastole > 2.3 is suggestive of LVNC with sensitivity and specificity of 86% and 99%.⁹

The management of LVNC focuses primarily on treatment of complications, including heart failure, rhythm disturbances, and thromboembolic events. Treatment of heart failure is typically the same as for other CMs and includes medical therapy with salt restriction, diuretics, beta-blockers, and ACE inhibitors. In addition, exercise training, as tolerated, is beneficial to improve clinical status.^3,10 Electrophysiology studies are often performed in these patients, and implantation of an AICD is typically done in cases of documented, sustained VT, presyncope with inducible VT or severally depressed ejection fraction of < 35%.^4,10 Deep intertrabecular recesses and impaired blood flow increase the risk of thrombus formation. Hence, anticoagulation with warfarin (international normalized ratio target 2.3) for those with an impaired LV ejection fraction (< 40%) should be considered for the prevention of cardioembolic events.^3,4,6,10

Summary

An active-duty solider with a history of battlefield trauma and multiple hospitalizations was admitted for symptomatic heart failure with cardiac MRI suggestive of LVNC. This condition is a phenotypic result of genetic heterogeneity with significant variability in clinical presentation and a predisposition for heart failure, ventricular arrhythmias, and systemic embolic events. The etiology of this patient’s clinical presentation remains unclear, and additional research is needed to understand whether his recent trauma and multiple hospitalizations played a role in the manifestation of his disease.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

The following case report describes the use of dexmedetomidine as the primary sedative for an awake endotracheal intubation, as an adjuvant for general anesthesia, and for postoperative sedation for mechanical ventilation. This case illustrates problems that  attracted the attention of federal institutions, specifically the management of difficult airways (with and without anatomic distortion), obesity, and obstructive sleep apnea (OSA). As such, it is of potential interest not only to anesthesiologists, but also  other health care providers in the VA, especially those who might practice in intensive care settings.

Dexmedetomidine has useful pharmacologic properties that have potential use in a wide variety of clinical scenarios. Dexmedetomidine is currently indicated for sedation in nonintubated patients before and during surgical and other procedures and in intubated and mechanically ventilated patients during treatment in an intensive care setting.

Large neck masses can produce numerous problems that complicate the anesthetic management in the intraoperative and immediate postoperative arenas. The adjuvant use of dexmedetomidine, an alpha-2 agonist that has useful properties for both the anesthetic and intensive care situations, will be discussed. The problems involved with the management and resection of large neck masses include tracheal deviation, tracheal compression, airway edema, distorted anatomy, difficult mask ventilation, difficult intubation, postoperative recurrent laryngeal nerve dysfunction, and difficult exposure for tracheostomy.

Case Report

A 46-year-old man was referred for removal of a large thyroid mass. His past medical history included hypertension, obesity, and type 2 diabetes mellitus. Clinically, the patient seemed to be at risk for OSA, but he had not received a formal diagnosis. The patient met many of the criteria for screening OSA that are listed for a STOP-Bang Questionnaire.¹ He was clinically and serologically euthyroid. Neck ultrasound revealed a very large thyroid mass with cystic and solid lesions throughout. Other than hoarseness, the patient reported no compressive symptoms, such as dysphagia or airway compromise. He was maintained on metoprolol, fosinopril, a thiazide for hypertension, and metformin and insulin for diabetes. A physical examination was remarkable for a Mallampati IV airway classification, a 61-cm neck circumference, 177 cm height, 142 kg weight, and a body mass index of 45. These preoperative assessments were predictive of a high probability of very difficult mask ventilation and intubation after the induction of a general anesthetic, or in any other situation requiring tracheal intubation, such as respiratory failure in the postoperative period.

Preoperative laboratory studies, chest radiograph, and electrocardiogram (ECG) were unremarkable. Computed tomography (CT) imaging of the neck revealed marked enlargement of the thyroid, which had a multinodular, heterogeneous appearance with scattered calcifications. The left lobe of the thyroid measured 13.0 cm craniocaudal by 9.47 cm transverse by 6.8 cm anteroposterior. The right lobe of the thyroid measured 12.0 cm craniocaudal by 7.6 cm transverse by 7.0 cm anteroposterior (Figure 1).

The first concern for this patient was a secure airway, which potentially could have been very difficult to procure with a standard IV induction of anesthesia followed by a direct laryngoscopy. This was further constrained by the surgical requirement that the patient be intubated with an electromyography (EMG) endotracheal tube for monitoring of the recurrent laryngeal nerves, as thyroid surgery carries the risk of injury to these nerves. The type of tube that was used had a larger diameter than that of a standard endotracheal tube (the EMG tube measured 10.2 mm outside diameter vs 9.6 mm outside diameter for a standard tube) but was also far more rigid, precluding nasal intubation and making navigation of the tip around corners and obstructions more difficult. A final laryngoscopy was also needed for confirmation of optimal electrode placement at the vocal cord level (Figure 2).

The anesthetic  plan was to secure the airway with an awake oral fiberoptic intubation under sedation and topical local anesthetic to avoid the hypoxemia that would ensue if the patient lost spontaneous respiration. The patient was brought without preoperative sedation to the operating room, standard monitors (eg, ECG, noninvasive blood pressure, pulse oximetry) were applied and IV access was obtained. Blood pressure, heart rate, and oxygen saturation were within normal limits. He was placed on oxygen 2 L/min by nasal cannula and given a 1 μg/kg loading dose of dexmedetomidine over 10 minutes and thereafter maintained on a 0.4 μg/kg/h maintenance infusion during the entire airway intubation sequence. A topical anesthesia of 4% lidocaine spray was applied to the upper airway, and a transtracheal injection was performed with 2 mL of 4% lidocaine. The patient’s anatomy precluded the use of superior laryngeal nerve blocks. During the dexmedetomidine loading, he was given 1 mg midazolam and 100 μg fentanyl IV incrementally. No significant hemodynamic or respiratory changes occurred with this sedation regimen.

An attempt to place an oral intubation bite block failed, because the stiff EMG tube proved too difficult to pass through it. Therefore, the EMG tube and rolled gauze pads placed between the upper and lower teeth were used to protect the fiberoptic bronchoscope while it was guided past the base of the tongue. As was noted in the CT scan, the airway was deviated slightly to the left, and this information was useful for guiding the fiberscope. The location of the epiglottis was fairly difficult to ascertain due to redundant tissue in the hypopharyngeal area but was ultimately visible through the fiberscope.

The vocal cords were not visible, possibly due to the significant amount of airway edema and/or redundant tissue between the epiglottis and the vocal cords: Only the space beneath the epiglottis could be seen via the fiberscope. Passing the bronchoscope through the larynx also was problematic due to what may be described as altered spatial/angular relationships and due to the supraglottic edema/tissue leaving little room for the tip of the bronchoscope to be maneuvered. Figure 3 shows a CT scan image of the supraglottic area.

It took 45 minutes and multiple attempts to pass the bronchoscope into the trachea. The dexmedetomidine infusion was continued throughout this entire sequence. The patient tolerated this manipulation with little difficulty, despite the multiple airway maneuvers, and his hemodynamic and respiratory status remained clinically stable. Oxygen saturation was 95% to 100% during this sequence and the patient did not show evidence of significant upper airway collapse, desaturation, or apnea, which are sometimes encountered during sedation for airway manipulation.

The patient’s hemodynamic status remained near baseline values throughout the airway manipulation. The patient never lost his ability to cooperate. After manipulation of the fiberscope into the trachea, the tracheal rings and carina were visualized, and the tube was advanced over the scope. Minimal to mild coughing occurred once the tube passed through the vocal cords. The tube position in the trachea was verified with end-tidal CO₂ and bronchoscopy and then the induction of anesthesia with propofol was completed. A laryngoscopy using a videolaryngoscope confirmed proper EMG electrode placement. Large-bore IV access and an arterial line were then secured.

The operation lasted about 15 hours. Maintenance of anesthesia was accomplished with the use of the volatile anesthetic desflurane, titrated to patient response to the surgical procedure. Additionally, 550 μg of IV fentanyl was used intermittently during the operation. Dexmedetomidine was infused at a rate of 0.2 to 0.4 μg/kg/h during the anesthetic, titrated to hemodynamic response. All hemodynamic parameters remained stable and within 20% of preoperative levels during the procedure. The blood loss during the procedure was minimal (< 100 mL), and acceptable readings from the EMG tube were confirmed throughout the surgical procedure.

The 686-gram thyroid mass was confirmed to be a multinodular goiter. Due to the difficulty with intubation, the length of the surgical procedure, and the likelihood of airway difficulties from edema possibly requiring reintubation, the patient was left intubated and mechanically ventilated overnight and sedated with a dexmedetomidine infusion of 0.3 μg/kg/h and propofol 35 mL/h. No further medications were required. He tolerated the ventilator without fighting, straining, coughing, or hypertensive responses and remained cooperative when aroused. He was successfully extubated the following day. Afterward, the patient maintained his airway and had only a mild right vocal cord paresis complicating his surgical management.

Discussion

The critical issues associated with this successful endotracheal intubation included the patient’s obesity, thyroid mass size, and deviation/compression of the trachea. Were this patient morbidly obese only, airway management would still be problematic; this was exacerbated by the concurrent pathologies. Dexmedetomidine possesses several advantageous properties for the perioperative period and was chosen as sedation for the awake intubation due to its sedative-analgesic effects, opioid sparing effects, lack of respiratory depression, maintenance of patient cooperation, and antisialagogue effect.^2-5 Dexmedetomidine has previously been shown to be useful for awake intubation of difficult airway cases.^4,6,7 Importantly, the dexmedetomidine sedation seemed to blunt the hypertensive responses often seen during airway maneuvers.⁸ It was also chosen as an intraoperative adjunct due to the above-noted opioid-sparing effects, given the importance of minimizing perioperative opioids needed for this morbidly obese individual with airway compromise.

In the literature, dexmedetomidine has been shown to greatly reduce the need for opioids, both intraoperatively and immediately postoperatively in many citations, for example, in postoperative mechanically ventilated coronary artery bypass graft patients.^2,9 Opioid usage reduction is especially needed for the morbidly obese who are at increased risk of OSA and the attendant increased sensitivity to the respiratory depressant effects of narcotics. Postoperative opioids are being debated in the literature as potentially being a risk factor for cancer recurrence due to the effects on the immune system.^5,10

Although the pathology report was benign for this patient, it was thought that prior to the surgery a reduction in opioid usage was important because he may have had a thyroid carcinoma in addition to the other respiratory considerations. Additionally, it was desired to decrease the amount of volatile anesthetic agents needed for this patient, because the surgical procedure was anticipated to be quite prolonged (it lasted 15 hours).

Conclusions

Recent research showed that a dexmedetomidine infusion combined with a low-dosage midazolam was superior to a higher dosage midazolam regimen for awake fiberoptic intubation in terms of stability, comfort, cooperation, and patient satisfaction.¹¹ This is an example of the utility of dexmedetomidine. It is often insufficient when used alone, but as an adjunct will markedly reduce the dosage of other sedatives needed to achieve the desired Ramsey sedation scores and/or clinical benefit. Additionally, dexmedetomidine has been shown to facilitate weaning patients in a case series (who had previously failed weaning) from mechanical ventilation in surgical intensive care settings.¹²

The use of dexmedetomidine facilitated awake intubation for this patient and was helpful for postoperative sedation. The authors believe that dexmedetomidine has potential benefits in all phases of surgery and is a potentially valuable addition to the anesthesiologist’s and intensivist’s armamentarium.  

Acknowledgements
This work was conducted at and supported by the G.V. (Sonny) Montgomery VA Medical Center in Jackson, Mississippi.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

The following case report describes the use of dexmedetomidine as the primary sedative for an awake endotracheal intubation, as an adjuvant for general anesthesia, and for postoperative sedation for mechanical ventilation. This case illustrates problems that  attracted the attention of federal institutions, specifically the management of difficult airways (with and without anatomic distortion), obesity, and obstructive sleep apnea (OSA). As such, it is of potential interest not only to anesthesiologists, but also  other health care providers in the VA, especially those who might practice in intensive care settings.

Dexmedetomidine has useful pharmacologic properties that have potential use in a wide variety of clinical scenarios. Dexmedetomidine is currently indicated for sedation in nonintubated patients before and during surgical and other procedures and in intubated and mechanically ventilated patients during treatment in an intensive care setting.

Large neck masses can produce numerous problems that complicate the anesthetic management in the intraoperative and immediate postoperative arenas. The adjuvant use of dexmedetomidine, an alpha-2 agonist that has useful properties for both the anesthetic and intensive care situations, will be discussed. The problems involved with the management and resection of large neck masses include tracheal deviation, tracheal compression, airway edema, distorted anatomy, difficult mask ventilation, difficult intubation, postoperative recurrent laryngeal nerve dysfunction, and difficult exposure for tracheostomy.

Case Report

A 46-year-old man was referred for removal of a large thyroid mass. His past medical history included hypertension, obesity, and type 2 diabetes mellitus. Clinically, the patient seemed to be at risk for OSA, but he had not received a formal diagnosis. The patient met many of the criteria for screening OSA that are listed for a STOP-Bang Questionnaire.¹ He was clinically and serologically euthyroid. Neck ultrasound revealed a very large thyroid mass with cystic and solid lesions throughout. Other than hoarseness, the patient reported no compressive symptoms, such as dysphagia or airway compromise. He was maintained on metoprolol, fosinopril, a thiazide for hypertension, and metformin and insulin for diabetes. A physical examination was remarkable for a Mallampati IV airway classification, a 61-cm neck circumference, 177 cm height, 142 kg weight, and a body mass index of 45. These preoperative assessments were predictive of a high probability of very difficult mask ventilation and intubation after the induction of a general anesthetic, or in any other situation requiring tracheal intubation, such as respiratory failure in the postoperative period.

Preoperative laboratory studies, chest radiograph, and electrocardiogram (ECG) were unremarkable. Computed tomography (CT) imaging of the neck revealed marked enlargement of the thyroid, which had a multinodular, heterogeneous appearance with scattered calcifications. The left lobe of the thyroid measured 13.0 cm craniocaudal by 9.47 cm transverse by 6.8 cm anteroposterior. The right lobe of the thyroid measured 12.0 cm craniocaudal by 7.6 cm transverse by 7.0 cm anteroposterior (Figure 1).

The first concern for this patient was a secure airway, which potentially could have been very difficult to procure with a standard IV induction of anesthesia followed by a direct laryngoscopy. This was further constrained by the surgical requirement that the patient be intubated with an electromyography (EMG) endotracheal tube for monitoring of the recurrent laryngeal nerves, as thyroid surgery carries the risk of injury to these nerves. The type of tube that was used had a larger diameter than that of a standard endotracheal tube (the EMG tube measured 10.2 mm outside diameter vs 9.6 mm outside diameter for a standard tube) but was also far more rigid, precluding nasal intubation and making navigation of the tip around corners and obstructions more difficult. A final laryngoscopy was also needed for confirmation of optimal electrode placement at the vocal cord level (Figure 2).

The anesthetic  plan was to secure the airway with an awake oral fiberoptic intubation under sedation and topical local anesthetic to avoid the hypoxemia that would ensue if the patient lost spontaneous respiration. The patient was brought without preoperative sedation to the operating room, standard monitors (eg, ECG, noninvasive blood pressure, pulse oximetry) were applied and IV access was obtained. Blood pressure, heart rate, and oxygen saturation were within normal limits. He was placed on oxygen 2 L/min by nasal cannula and given a 1 μg/kg loading dose of dexmedetomidine over 10 minutes and thereafter maintained on a 0.4 μg/kg/h maintenance infusion during the entire airway intubation sequence. A topical anesthesia of 4% lidocaine spray was applied to the upper airway, and a transtracheal injection was performed with 2 mL of 4% lidocaine. The patient’s anatomy precluded the use of superior laryngeal nerve blocks. During the dexmedetomidine loading, he was given 1 mg midazolam and 100 μg fentanyl IV incrementally. No significant hemodynamic or respiratory changes occurred with this sedation regimen.

An attempt to place an oral intubation bite block failed, because the stiff EMG tube proved too difficult to pass through it. Therefore, the EMG tube and rolled gauze pads placed between the upper and lower teeth were used to protect the fiberoptic bronchoscope while it was guided past the base of the tongue. As was noted in the CT scan, the airway was deviated slightly to the left, and this information was useful for guiding the fiberscope. The location of the epiglottis was fairly difficult to ascertain due to redundant tissue in the hypopharyngeal area but was ultimately visible through the fiberscope.

The vocal cords were not visible, possibly due to the significant amount of airway edema and/or redundant tissue between the epiglottis and the vocal cords: Only the space beneath the epiglottis could be seen via the fiberscope. Passing the bronchoscope through the larynx also was problematic due to what may be described as altered spatial/angular relationships and due to the supraglottic edema/tissue leaving little room for the tip of the bronchoscope to be maneuvered. Figure 3 shows a CT scan image of the supraglottic area.

It took 45 minutes and multiple attempts to pass the bronchoscope into the trachea. The dexmedetomidine infusion was continued throughout this entire sequence. The patient tolerated this manipulation with little difficulty, despite the multiple airway maneuvers, and his hemodynamic and respiratory status remained clinically stable. Oxygen saturation was 95% to 100% during this sequence and the patient did not show evidence of significant upper airway collapse, desaturation, or apnea, which are sometimes encountered during sedation for airway manipulation.

The patient’s hemodynamic status remained near baseline values throughout the airway manipulation. The patient never lost his ability to cooperate. After manipulation of the fiberscope into the trachea, the tracheal rings and carina were visualized, and the tube was advanced over the scope. Minimal to mild coughing occurred once the tube passed through the vocal cords. The tube position in the trachea was verified with end-tidal CO₂ and bronchoscopy and then the induction of anesthesia with propofol was completed. A laryngoscopy using a videolaryngoscope confirmed proper EMG electrode placement. Large-bore IV access and an arterial line were then secured.

The operation lasted about 15 hours. Maintenance of anesthesia was accomplished with the use of the volatile anesthetic desflurane, titrated to patient response to the surgical procedure. Additionally, 550 μg of IV fentanyl was used intermittently during the operation. Dexmedetomidine was infused at a rate of 0.2 to 0.4 μg/kg/h during the anesthetic, titrated to hemodynamic response. All hemodynamic parameters remained stable and within 20% of preoperative levels during the procedure. The blood loss during the procedure was minimal (< 100 mL), and acceptable readings from the EMG tube were confirmed throughout the surgical procedure.

The 686-gram thyroid mass was confirmed to be a multinodular goiter. Due to the difficulty with intubation, the length of the surgical procedure, and the likelihood of airway difficulties from edema possibly requiring reintubation, the patient was left intubated and mechanically ventilated overnight and sedated with a dexmedetomidine infusion of 0.3 μg/kg/h and propofol 35 mL/h. No further medications were required. He tolerated the ventilator without fighting, straining, coughing, or hypertensive responses and remained cooperative when aroused. He was successfully extubated the following day. Afterward, the patient maintained his airway and had only a mild right vocal cord paresis complicating his surgical management.

Discussion

The critical issues associated with this successful endotracheal intubation included the patient’s obesity, thyroid mass size, and deviation/compression of the trachea. Were this patient morbidly obese only, airway management would still be problematic; this was exacerbated by the concurrent pathologies. Dexmedetomidine possesses several advantageous properties for the perioperative period and was chosen as sedation for the awake intubation due to its sedative-analgesic effects, opioid sparing effects, lack of respiratory depression, maintenance of patient cooperation, and antisialagogue effect.^2-5 Dexmedetomidine has previously been shown to be useful for awake intubation of difficult airway cases.^4,6,7 Importantly, the dexmedetomidine sedation seemed to blunt the hypertensive responses often seen during airway maneuvers.⁸ It was also chosen as an intraoperative adjunct due to the above-noted opioid-sparing effects, given the importance of minimizing perioperative opioids needed for this morbidly obese individual with airway compromise.

In the literature, dexmedetomidine has been shown to greatly reduce the need for opioids, both intraoperatively and immediately postoperatively in many citations, for example, in postoperative mechanically ventilated coronary artery bypass graft patients.^2,9 Opioid usage reduction is especially needed for the morbidly obese who are at increased risk of OSA and the attendant increased sensitivity to the respiratory depressant effects of narcotics. Postoperative opioids are being debated in the literature as potentially being a risk factor for cancer recurrence due to the effects on the immune system.^5,10

Although the pathology report was benign for this patient, it was thought that prior to the surgery a reduction in opioid usage was important because he may have had a thyroid carcinoma in addition to the other respiratory considerations. Additionally, it was desired to decrease the amount of volatile anesthetic agents needed for this patient, because the surgical procedure was anticipated to be quite prolonged (it lasted 15 hours).

Conclusions

Recent research showed that a dexmedetomidine infusion combined with a low-dosage midazolam was superior to a higher dosage midazolam regimen for awake fiberoptic intubation in terms of stability, comfort, cooperation, and patient satisfaction.¹¹ This is an example of the utility of dexmedetomidine. It is often insufficient when used alone, but as an adjunct will markedly reduce the dosage of other sedatives needed to achieve the desired Ramsey sedation scores and/or clinical benefit. Additionally, dexmedetomidine has been shown to facilitate weaning patients in a case series (who had previously failed weaning) from mechanical ventilation in surgical intensive care settings.¹²

The use of dexmedetomidine facilitated awake intubation for this patient and was helpful for postoperative sedation. The authors believe that dexmedetomidine has potential benefits in all phases of surgery and is a potentially valuable addition to the anesthesiologist’s and intensivist’s armamentarium.  

Acknowledgements
This work was conducted at and supported by the G.V. (Sonny) Montgomery VA Medical Center in Jackson, Mississippi.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

The following case report describes the use of dexmedetomidine as the primary sedative for an awake endotracheal intubation, as an adjuvant for general anesthesia, and for postoperative sedation for mechanical ventilation. This case illustrates problems that  attracted the attention of federal institutions, specifically the management of difficult airways (with and without anatomic distortion), obesity, and obstructive sleep apnea (OSA). As such, it is of potential interest not only to anesthesiologists, but also  other health care providers in the VA, especially those who might practice in intensive care settings.

Dexmedetomidine has useful pharmacologic properties that have potential use in a wide variety of clinical scenarios. Dexmedetomidine is currently indicated for sedation in nonintubated patients before and during surgical and other procedures and in intubated and mechanically ventilated patients during treatment in an intensive care setting.

Large neck masses can produce numerous problems that complicate the anesthetic management in the intraoperative and immediate postoperative arenas. The adjuvant use of dexmedetomidine, an alpha-2 agonist that has useful properties for both the anesthetic and intensive care situations, will be discussed. The problems involved with the management and resection of large neck masses include tracheal deviation, tracheal compression, airway edema, distorted anatomy, difficult mask ventilation, difficult intubation, postoperative recurrent laryngeal nerve dysfunction, and difficult exposure for tracheostomy.

Case Report

A 46-year-old man was referred for removal of a large thyroid mass. His past medical history included hypertension, obesity, and type 2 diabetes mellitus. Clinically, the patient seemed to be at risk for OSA, but he had not received a formal diagnosis. The patient met many of the criteria for screening OSA that are listed for a STOP-Bang Questionnaire.¹ He was clinically and serologically euthyroid. Neck ultrasound revealed a very large thyroid mass with cystic and solid lesions throughout. Other than hoarseness, the patient reported no compressive symptoms, such as dysphagia or airway compromise. He was maintained on metoprolol, fosinopril, a thiazide for hypertension, and metformin and insulin for diabetes. A physical examination was remarkable for a Mallampati IV airway classification, a 61-cm neck circumference, 177 cm height, 142 kg weight, and a body mass index of 45. These preoperative assessments were predictive of a high probability of very difficult mask ventilation and intubation after the induction of a general anesthetic, or in any other situation requiring tracheal intubation, such as respiratory failure in the postoperative period.

Preoperative laboratory studies, chest radiograph, and electrocardiogram (ECG) were unremarkable. Computed tomography (CT) imaging of the neck revealed marked enlargement of the thyroid, which had a multinodular, heterogeneous appearance with scattered calcifications. The left lobe of the thyroid measured 13.0 cm craniocaudal by 9.47 cm transverse by 6.8 cm anteroposterior. The right lobe of the thyroid measured 12.0 cm craniocaudal by 7.6 cm transverse by 7.0 cm anteroposterior (Figure 1).

The first concern for this patient was a secure airway, which potentially could have been very difficult to procure with a standard IV induction of anesthesia followed by a direct laryngoscopy. This was further constrained by the surgical requirement that the patient be intubated with an electromyography (EMG) endotracheal tube for monitoring of the recurrent laryngeal nerves, as thyroid surgery carries the risk of injury to these nerves. The type of tube that was used had a larger diameter than that of a standard endotracheal tube (the EMG tube measured 10.2 mm outside diameter vs 9.6 mm outside diameter for a standard tube) but was also far more rigid, precluding nasal intubation and making navigation of the tip around corners and obstructions more difficult. A final laryngoscopy was also needed for confirmation of optimal electrode placement at the vocal cord level (Figure 2).

The anesthetic  plan was to secure the airway with an awake oral fiberoptic intubation under sedation and topical local anesthetic to avoid the hypoxemia that would ensue if the patient lost spontaneous respiration. The patient was brought without preoperative sedation to the operating room, standard monitors (eg, ECG, noninvasive blood pressure, pulse oximetry) were applied and IV access was obtained. Blood pressure, heart rate, and oxygen saturation were within normal limits. He was placed on oxygen 2 L/min by nasal cannula and given a 1 μg/kg loading dose of dexmedetomidine over 10 minutes and thereafter maintained on a 0.4 μg/kg/h maintenance infusion during the entire airway intubation sequence. A topical anesthesia of 4% lidocaine spray was applied to the upper airway, and a transtracheal injection was performed with 2 mL of 4% lidocaine. The patient’s anatomy precluded the use of superior laryngeal nerve blocks. During the dexmedetomidine loading, he was given 1 mg midazolam and 100 μg fentanyl IV incrementally. No significant hemodynamic or respiratory changes occurred with this sedation regimen.

An attempt to place an oral intubation bite block failed, because the stiff EMG tube proved too difficult to pass through it. Therefore, the EMG tube and rolled gauze pads placed between the upper and lower teeth were used to protect the fiberoptic bronchoscope while it was guided past the base of the tongue. As was noted in the CT scan, the airway was deviated slightly to the left, and this information was useful for guiding the fiberscope. The location of the epiglottis was fairly difficult to ascertain due to redundant tissue in the hypopharyngeal area but was ultimately visible through the fiberscope.

The vocal cords were not visible, possibly due to the significant amount of airway edema and/or redundant tissue between the epiglottis and the vocal cords: Only the space beneath the epiglottis could be seen via the fiberscope. Passing the bronchoscope through the larynx also was problematic due to what may be described as altered spatial/angular relationships and due to the supraglottic edema/tissue leaving little room for the tip of the bronchoscope to be maneuvered. Figure 3 shows a CT scan image of the supraglottic area.

It took 45 minutes and multiple attempts to pass the bronchoscope into the trachea. The dexmedetomidine infusion was continued throughout this entire sequence. The patient tolerated this manipulation with little difficulty, despite the multiple airway maneuvers, and his hemodynamic and respiratory status remained clinically stable. Oxygen saturation was 95% to 100% during this sequence and the patient did not show evidence of significant upper airway collapse, desaturation, or apnea, which are sometimes encountered during sedation for airway manipulation.

The patient’s hemodynamic status remained near baseline values throughout the airway manipulation. The patient never lost his ability to cooperate. After manipulation of the fiberscope into the trachea, the tracheal rings and carina were visualized, and the tube was advanced over the scope. Minimal to mild coughing occurred once the tube passed through the vocal cords. The tube position in the trachea was verified with end-tidal CO₂ and bronchoscopy and then the induction of anesthesia with propofol was completed. A laryngoscopy using a videolaryngoscope confirmed proper EMG electrode placement. Large-bore IV access and an arterial line were then secured.

The operation lasted about 15 hours. Maintenance of anesthesia was accomplished with the use of the volatile anesthetic desflurane, titrated to patient response to the surgical procedure. Additionally, 550 μg of IV fentanyl was used intermittently during the operation. Dexmedetomidine was infused at a rate of 0.2 to 0.4 μg/kg/h during the anesthetic, titrated to hemodynamic response. All hemodynamic parameters remained stable and within 20% of preoperative levels during the procedure. The blood loss during the procedure was minimal (< 100 mL), and acceptable readings from the EMG tube were confirmed throughout the surgical procedure.

The 686-gram thyroid mass was confirmed to be a multinodular goiter. Due to the difficulty with intubation, the length of the surgical procedure, and the likelihood of airway difficulties from edema possibly requiring reintubation, the patient was left intubated and mechanically ventilated overnight and sedated with a dexmedetomidine infusion of 0.3 μg/kg/h and propofol 35 mL/h. No further medications were required. He tolerated the ventilator without fighting, straining, coughing, or hypertensive responses and remained cooperative when aroused. He was successfully extubated the following day. Afterward, the patient maintained his airway and had only a mild right vocal cord paresis complicating his surgical management.

Discussion

The critical issues associated with this successful endotracheal intubation included the patient’s obesity, thyroid mass size, and deviation/compression of the trachea. Were this patient morbidly obese only, airway management would still be problematic; this was exacerbated by the concurrent pathologies. Dexmedetomidine possesses several advantageous properties for the perioperative period and was chosen as sedation for the awake intubation due to its sedative-analgesic effects, opioid sparing effects, lack of respiratory depression, maintenance of patient cooperation, and antisialagogue effect.^2-5 Dexmedetomidine has previously been shown to be useful for awake intubation of difficult airway cases.^4,6,7 Importantly, the dexmedetomidine sedation seemed to blunt the hypertensive responses often seen during airway maneuvers.⁸ It was also chosen as an intraoperative adjunct due to the above-noted opioid-sparing effects, given the importance of minimizing perioperative opioids needed for this morbidly obese individual with airway compromise.

In the literature, dexmedetomidine has been shown to greatly reduce the need for opioids, both intraoperatively and immediately postoperatively in many citations, for example, in postoperative mechanically ventilated coronary artery bypass graft patients.^2,9 Opioid usage reduction is especially needed for the morbidly obese who are at increased risk of OSA and the attendant increased sensitivity to the respiratory depressant effects of narcotics. Postoperative opioids are being debated in the literature as potentially being a risk factor for cancer recurrence due to the effects on the immune system.^5,10

Although the pathology report was benign for this patient, it was thought that prior to the surgery a reduction in opioid usage was important because he may have had a thyroid carcinoma in addition to the other respiratory considerations. Additionally, it was desired to decrease the amount of volatile anesthetic agents needed for this patient, because the surgical procedure was anticipated to be quite prolonged (it lasted 15 hours).

Conclusions

Recent research showed that a dexmedetomidine infusion combined with a low-dosage midazolam was superior to a higher dosage midazolam regimen for awake fiberoptic intubation in terms of stability, comfort, cooperation, and patient satisfaction.¹¹ This is an example of the utility of dexmedetomidine. It is often insufficient when used alone, but as an adjunct will markedly reduce the dosage of other sedatives needed to achieve the desired Ramsey sedation scores and/or clinical benefit. Additionally, dexmedetomidine has been shown to facilitate weaning patients in a case series (who had previously failed weaning) from mechanical ventilation in surgical intensive care settings.¹²

The use of dexmedetomidine facilitated awake intubation for this patient and was helpful for postoperative sedation. The authors believe that dexmedetomidine has potential benefits in all phases of surgery and is a potentially valuable addition to the anesthesiologist’s and intensivist’s armamentarium.  

Acknowledgements
This work was conducted at and supported by the G.V. (Sonny) Montgomery VA Medical Center in Jackson, Mississippi.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Diabetes mellitus is a growing problem in the U.S., with the number of disease-related complications on the rise. It affects 29.1 million people of all ages; however, only 21 million people are diagnosed, leaving 8.1 million people undiagnosed.¹ Heart disease death rates among adults with diabetes are 2 to 4 times higher than the rates for adults without diabetes.² At least 68% of patients with diabetes aged > 65 years die of some form of heart disease; 16% die of stroke.²

Type 2 diabetes remains the leading cause for cardiovascular disorders, blindness, end-stage renal disease, amputations, and hospitalizations.³ Due to the long-term complications of diabetes, it is important to help patients control their disease. However, diabetes control in patients can be difficult because of the broad disease education needed and its medication administration.

Insulin requires the most extensive instruction when educating patients with diabetes. Specifically, patient counseling needs to incorporate the importance of proper insulin administration. If patients are not properly administering their insulin, controlling their diabetes will be very difficult. Many clinicians know to educate the patient about drawing insulin into a syringe and how to inject insulin properly. However, clinicians do not always think about other aspects of insulin administration education, such as the mixing of different insulins in 1 syringe. Patients and family members need to be taught about the types of insulins that can and cannot be mixed. The American Diabetes Association (ADA) provides recommendations on the appropriate time to mix insulin and the types of insulin that can and cannot be mixed (Table 1).⁴

CASE REPORT

A white male, aged 69 years, presented to a pharmacist-run pharmacotherapy clinic for a follow-up appointment for uncontrolled diabetes. The patient’s wife, who managed his medications, accompanied him. Significant past medical history included diabetes, nephropathy, retinopathy, degenerative joint disease, migraines, gastroesophageal reflux disease, depression, posttraumatic stress disorder, hyperlipidemia, hypertension, lumbago, panic attacks, medication noncompliance, status post cerebral vascular accident, and renal insufficiency.

The patient had a long history of  type 2 diabetes, and his insulin had been titrated multiple times since he was established in this clinic in 2009. At his establishing visit, he was taken off his insulin pump due to noncompliance with blood glucose checks and placed on basal-bolus therapy with insulin glargine and insulin aspart. The patient then titrated his basal-bolus insulin for 6 weeks but stated his blood sugars were consistently elevated (reaching 600 mg/dL); therefore, he self-reinitiated the insulin pump. After restarting the insulin pump, the clinic made several attempts to follow-up with the patient, but none were successful. He was subsequently dismissed from the clinic following his admission to a local nursing home.

The patient was reestablished at the clinic in 2010 (about 1 year after dismissal). He reported discontinuing the insulin pump and using insulin glargine and insulin aspart injections but was self-adjusting insulin glargine based on readings. He was told not to self-adjust insulin glargine dose and was given a sliding scale for self-adjustment of his insulin aspart dose based on blood glucose readings. Since the reestablished visit, both insulin therapies were titrated without much success in controlling his blood glucose levels. He was also advised to check his fasting blood glucose (FBG) more often and was demonstrated correct insulin drawing technique.

At a follow-up visit in August 2012, the patient’s A_1c was 10.7%, and FBG readings ranged from 108 mg/dL to 555 mg/dL. Goal A_1c was between 8% and 8.5% per VA/DoD diabetes guidelines.⁵ After a discussion with the patient’s wife, it was discovered that the patient was improperly administrating his insulin. The patient had been administrating the insulin glargine and insulin aspart in the same syringe. Since the combined dose of insulin was greater than his syringe would allow, he adjusted the insulin glargine dose downward if more insulin aspart was needed per the sliding scale. He did this to avoid more injections than he thought were necessary. Based on his A_1c and home blood glucose readings, it was also suspected that insulin doses were being missed. The patient and wife were instructed about the importance of adherence and not mixing these insulins in the same syringe.

At the most recent visit, the patient’s FBG readings (200 mg/dL-500 mg/dL) and A_1c (10.7%) were still greatly elevated. He reported taking 40 units insulin glargine in the morning and 60 units at bedtime, along with 40 units insulin aspart plus sliding scale insulin (1:20 > 120 mg/dL) at breakfast and 40 to 70 units at lunch and supper. The patient reported compliance with insulin therapy; however, it was likely he was not dosing accurately, according to his sliding scale. He stated he was eating less and was worried about hypoglycemia. Due to the patient’s FBG and A_1c still being elevated, insulin aspart was titrated again, which was closer to a 50% basal and 50% bolus regimen, and he was again educated about proper dosing.

DISCUSSION

Patients have many obstacles to managing their diseases. This is especially prevalent in patients with diabetes. These patients both experience the emotional stress of being diagnosed with diabetes and are given a wealth of information on diabetes, nutrition, therapy, and insulin-dosing technique at the same time. The information can be overwhelming for patients to hear and for the educator to present. Sometimes health care professionals (HCPs) overlook a patient’s hindrances due to the amount of information they have to give to the patient. For example, in this case, the patient was mixing insulin inappropriately, and it was overlooked by the HCP.

Insulin therapy has been used for several decades. It is obtained from either a pork pancreas or is chemically manufactured to be identical to human insulin. This can be achieved by recombinant DNA technology or chemical modification of pork insulin.⁴ Insulin is available as short-, intermediate-, or long-acting duration. The pharmacokinetics of available insulins is listed in Table 2.⁶

Some insulin can be mixed in the same syringe, but these mainly consist of the short- and intermediate-acting insulin. Insulin glargine, a long-acting formulation, should not be mixed with any other insulin due to its pharmacokinetic properties.⁷ Insulin glargine has been designed to have a low solubility at a neutral pH. After injection, the pH rises and leads to the formation of microprecipitates, causing a slow release of the insulin over 24 hours with no peak. If insulin glargine is mixed, it is likely the pH would be altered before entering the body. In addition, mixing insulin in the same syringe could likely contaminate the dose.

The maker of insulin glargine advises against mixing it with any other insulin.⁷ Several different studies have been done with admixtures of insulin glargine with short- or rapid-acting insulin. The studies revealed no differences in glycemic control, blunted and delayed rapid-acting insulin peak, the need for larger doses, or worsened glycemic control.^8-12

Other education points about insulin administration that are often overlooked or sometimes ignored by patients and that require follow-up for compliance include the following:

• Manufacturers recommend discarding an open bottle of insulin at room temperature after 28 days.⁷

• Insulin should be kept in a temperature-controlled environment between 36°F and 86°F.^4,7

• Rotation of injection sites is necessary to prevent lipodystrophy.^4,7

• It is recommended that patients stick with 1 approved anatomical site for all insulin injections, such as the abdomen or leg, to maintain consistent pharmacokinetics.^4,13,14

It is also important to know the constitution of the different insulins and whether they have been compromised. For example, if a clear solution insulin turns cloudy, it is considered compromised and should be thrown away.

CONCLUSION

Patients are diagnosed every day with diabetes, and many treatment regimens include insulin therapy. With the diagnosis of diabetes, patients are given extensive information on therapy, nutrition, preventative measures, and technique. Since controlling diabetes can call for intensive insulin therapy, medication administration instruction by HCPs is important. It is important to discuss in detail how the patient manages their insulin therapy at each visit so that issues will not be overlooked. Long-term, inappropriate use of insulin may lead to uncontrolled diabetes.

Diabetes is a complex disease to manage and takes a joint effort by both the HCP and patient to control. Patients need to understand the importance of compliance in all aspects of the disease, and the HCP needs to understand the importance of extensive counseling, including diet, exercise, and medication therapy. 

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Diabetes mellitus is a growing problem in the U.S., with the number of disease-related complications on the rise. It affects 29.1 million people of all ages; however, only 21 million people are diagnosed, leaving 8.1 million people undiagnosed.¹ Heart disease death rates among adults with diabetes are 2 to 4 times higher than the rates for adults without diabetes.² At least 68% of patients with diabetes aged > 65 years die of some form of heart disease; 16% die of stroke.²

Type 2 diabetes remains the leading cause for cardiovascular disorders, blindness, end-stage renal disease, amputations, and hospitalizations.³ Due to the long-term complications of diabetes, it is important to help patients control their disease. However, diabetes control in patients can be difficult because of the broad disease education needed and its medication administration.

Insulin requires the most extensive instruction when educating patients with diabetes. Specifically, patient counseling needs to incorporate the importance of proper insulin administration. If patients are not properly administering their insulin, controlling their diabetes will be very difficult. Many clinicians know to educate the patient about drawing insulin into a syringe and how to inject insulin properly. However, clinicians do not always think about other aspects of insulin administration education, such as the mixing of different insulins in 1 syringe. Patients and family members need to be taught about the types of insulins that can and cannot be mixed. The American Diabetes Association (ADA) provides recommendations on the appropriate time to mix insulin and the types of insulin that can and cannot be mixed (Table 1).⁴

CASE REPORT

A white male, aged 69 years, presented to a pharmacist-run pharmacotherapy clinic for a follow-up appointment for uncontrolled diabetes. The patient’s wife, who managed his medications, accompanied him. Significant past medical history included diabetes, nephropathy, retinopathy, degenerative joint disease, migraines, gastroesophageal reflux disease, depression, posttraumatic stress disorder, hyperlipidemia, hypertension, lumbago, panic attacks, medication noncompliance, status post cerebral vascular accident, and renal insufficiency.

The patient had a long history of  type 2 diabetes, and his insulin had been titrated multiple times since he was established in this clinic in 2009. At his establishing visit, he was taken off his insulin pump due to noncompliance with blood glucose checks and placed on basal-bolus therapy with insulin glargine and insulin aspart. The patient then titrated his basal-bolus insulin for 6 weeks but stated his blood sugars were consistently elevated (reaching 600 mg/dL); therefore, he self-reinitiated the insulin pump. After restarting the insulin pump, the clinic made several attempts to follow-up with the patient, but none were successful. He was subsequently dismissed from the clinic following his admission to a local nursing home.

The patient was reestablished at the clinic in 2010 (about 1 year after dismissal). He reported discontinuing the insulin pump and using insulin glargine and insulin aspart injections but was self-adjusting insulin glargine based on readings. He was told not to self-adjust insulin glargine dose and was given a sliding scale for self-adjustment of his insulin aspart dose based on blood glucose readings. Since the reestablished visit, both insulin therapies were titrated without much success in controlling his blood glucose levels. He was also advised to check his fasting blood glucose (FBG) more often and was demonstrated correct insulin drawing technique.

At a follow-up visit in August 2012, the patient’s A_1c was 10.7%, and FBG readings ranged from 108 mg/dL to 555 mg/dL. Goal A_1c was between 8% and 8.5% per VA/DoD diabetes guidelines.⁵ After a discussion with the patient’s wife, it was discovered that the patient was improperly administrating his insulin. The patient had been administrating the insulin glargine and insulin aspart in the same syringe. Since the combined dose of insulin was greater than his syringe would allow, he adjusted the insulin glargine dose downward if more insulin aspart was needed per the sliding scale. He did this to avoid more injections than he thought were necessary. Based on his A_1c and home blood glucose readings, it was also suspected that insulin doses were being missed. The patient and wife were instructed about the importance of adherence and not mixing these insulins in the same syringe.

At the most recent visit, the patient’s FBG readings (200 mg/dL-500 mg/dL) and A_1c (10.7%) were still greatly elevated. He reported taking 40 units insulin glargine in the morning and 60 units at bedtime, along with 40 units insulin aspart plus sliding scale insulin (1:20 > 120 mg/dL) at breakfast and 40 to 70 units at lunch and supper. The patient reported compliance with insulin therapy; however, it was likely he was not dosing accurately, according to his sliding scale. He stated he was eating less and was worried about hypoglycemia. Due to the patient’s FBG and A_1c still being elevated, insulin aspart was titrated again, which was closer to a 50% basal and 50% bolus regimen, and he was again educated about proper dosing.

DISCUSSION

Patients have many obstacles to managing their diseases. This is especially prevalent in patients with diabetes. These patients both experience the emotional stress of being diagnosed with diabetes and are given a wealth of information on diabetes, nutrition, therapy, and insulin-dosing technique at the same time. The information can be overwhelming for patients to hear and for the educator to present. Sometimes health care professionals (HCPs) overlook a patient’s hindrances due to the amount of information they have to give to the patient. For example, in this case, the patient was mixing insulin inappropriately, and it was overlooked by the HCP.

Insulin therapy has been used for several decades. It is obtained from either a pork pancreas or is chemically manufactured to be identical to human insulin. This can be achieved by recombinant DNA technology or chemical modification of pork insulin.⁴ Insulin is available as short-, intermediate-, or long-acting duration. The pharmacokinetics of available insulins is listed in Table 2.⁶

Some insulin can be mixed in the same syringe, but these mainly consist of the short- and intermediate-acting insulin. Insulin glargine, a long-acting formulation, should not be mixed with any other insulin due to its pharmacokinetic properties.⁷ Insulin glargine has been designed to have a low solubility at a neutral pH. After injection, the pH rises and leads to the formation of microprecipitates, causing a slow release of the insulin over 24 hours with no peak. If insulin glargine is mixed, it is likely the pH would be altered before entering the body. In addition, mixing insulin in the same syringe could likely contaminate the dose.

The maker of insulin glargine advises against mixing it with any other insulin.⁷ Several different studies have been done with admixtures of insulin glargine with short- or rapid-acting insulin. The studies revealed no differences in glycemic control, blunted and delayed rapid-acting insulin peak, the need for larger doses, or worsened glycemic control.^8-12

Other education points about insulin administration that are often overlooked or sometimes ignored by patients and that require follow-up for compliance include the following:

• Manufacturers recommend discarding an open bottle of insulin at room temperature after 28 days.⁷

• Insulin should be kept in a temperature-controlled environment between 36°F and 86°F.^4,7

• Rotation of injection sites is necessary to prevent lipodystrophy.^4,7

• It is recommended that patients stick with 1 approved anatomical site for all insulin injections, such as the abdomen or leg, to maintain consistent pharmacokinetics.^4,13,14

It is also important to know the constitution of the different insulins and whether they have been compromised. For example, if a clear solution insulin turns cloudy, it is considered compromised and should be thrown away.

CONCLUSION

Patients are diagnosed every day with diabetes, and many treatment regimens include insulin therapy. With the diagnosis of diabetes, patients are given extensive information on therapy, nutrition, preventative measures, and technique. Since controlling diabetes can call for intensive insulin therapy, medication administration instruction by HCPs is important. It is important to discuss in detail how the patient manages their insulin therapy at each visit so that issues will not be overlooked. Long-term, inappropriate use of insulin may lead to uncontrolled diabetes.

Diabetes is a complex disease to manage and takes a joint effort by both the HCP and patient to control. Patients need to understand the importance of compliance in all aspects of the disease, and the HCP needs to understand the importance of extensive counseling, including diet, exercise, and medication therapy. 

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Diabetes mellitus is a growing problem in the U.S., with the number of disease-related complications on the rise. It affects 29.1 million people of all ages; however, only 21 million people are diagnosed, leaving 8.1 million people undiagnosed.¹ Heart disease death rates among adults with diabetes are 2 to 4 times higher than the rates for adults without diabetes.² At least 68% of patients with diabetes aged > 65 years die of some form of heart disease; 16% die of stroke.²

Type 2 diabetes remains the leading cause for cardiovascular disorders, blindness, end-stage renal disease, amputations, and hospitalizations.³ Due to the long-term complications of diabetes, it is important to help patients control their disease. However, diabetes control in patients can be difficult because of the broad disease education needed and its medication administration.

Insulin requires the most extensive instruction when educating patients with diabetes. Specifically, patient counseling needs to incorporate the importance of proper insulin administration. If patients are not properly administering their insulin, controlling their diabetes will be very difficult. Many clinicians know to educate the patient about drawing insulin into a syringe and how to inject insulin properly. However, clinicians do not always think about other aspects of insulin administration education, such as the mixing of different insulins in 1 syringe. Patients and family members need to be taught about the types of insulins that can and cannot be mixed. The American Diabetes Association (ADA) provides recommendations on the appropriate time to mix insulin and the types of insulin that can and cannot be mixed (Table 1).⁴

CASE REPORT

A white male, aged 69 years, presented to a pharmacist-run pharmacotherapy clinic for a follow-up appointment for uncontrolled diabetes. The patient’s wife, who managed his medications, accompanied him. Significant past medical history included diabetes, nephropathy, retinopathy, degenerative joint disease, migraines, gastroesophageal reflux disease, depression, posttraumatic stress disorder, hyperlipidemia, hypertension, lumbago, panic attacks, medication noncompliance, status post cerebral vascular accident, and renal insufficiency.

The patient had a long history of  type 2 diabetes, and his insulin had been titrated multiple times since he was established in this clinic in 2009. At his establishing visit, he was taken off his insulin pump due to noncompliance with blood glucose checks and placed on basal-bolus therapy with insulin glargine and insulin aspart. The patient then titrated his basal-bolus insulin for 6 weeks but stated his blood sugars were consistently elevated (reaching 600 mg/dL); therefore, he self-reinitiated the insulin pump. After restarting the insulin pump, the clinic made several attempts to follow-up with the patient, but none were successful. He was subsequently dismissed from the clinic following his admission to a local nursing home.

The patient was reestablished at the clinic in 2010 (about 1 year after dismissal). He reported discontinuing the insulin pump and using insulin glargine and insulin aspart injections but was self-adjusting insulin glargine based on readings. He was told not to self-adjust insulin glargine dose and was given a sliding scale for self-adjustment of his insulin aspart dose based on blood glucose readings. Since the reestablished visit, both insulin therapies were titrated without much success in controlling his blood glucose levels. He was also advised to check his fasting blood glucose (FBG) more often and was demonstrated correct insulin drawing technique.

At a follow-up visit in August 2012, the patient’s A_1c was 10.7%, and FBG readings ranged from 108 mg/dL to 555 mg/dL. Goal A_1c was between 8% and 8.5% per VA/DoD diabetes guidelines.⁵ After a discussion with the patient’s wife, it was discovered that the patient was improperly administrating his insulin. The patient had been administrating the insulin glargine and insulin aspart in the same syringe. Since the combined dose of insulin was greater than his syringe would allow, he adjusted the insulin glargine dose downward if more insulin aspart was needed per the sliding scale. He did this to avoid more injections than he thought were necessary. Based on his A_1c and home blood glucose readings, it was also suspected that insulin doses were being missed. The patient and wife were instructed about the importance of adherence and not mixing these insulins in the same syringe.

At the most recent visit, the patient’s FBG readings (200 mg/dL-500 mg/dL) and A_1c (10.7%) were still greatly elevated. He reported taking 40 units insulin glargine in the morning and 60 units at bedtime, along with 40 units insulin aspart plus sliding scale insulin (1:20 > 120 mg/dL) at breakfast and 40 to 70 units at lunch and supper. The patient reported compliance with insulin therapy; however, it was likely he was not dosing accurately, according to his sliding scale. He stated he was eating less and was worried about hypoglycemia. Due to the patient’s FBG and A_1c still being elevated, insulin aspart was titrated again, which was closer to a 50% basal and 50% bolus regimen, and he was again educated about proper dosing.

DISCUSSION

Patients have many obstacles to managing their diseases. This is especially prevalent in patients with diabetes. These patients both experience the emotional stress of being diagnosed with diabetes and are given a wealth of information on diabetes, nutrition, therapy, and insulin-dosing technique at the same time. The information can be overwhelming for patients to hear and for the educator to present. Sometimes health care professionals (HCPs) overlook a patient’s hindrances due to the amount of information they have to give to the patient. For example, in this case, the patient was mixing insulin inappropriately, and it was overlooked by the HCP.

Insulin therapy has been used for several decades. It is obtained from either a pork pancreas or is chemically manufactured to be identical to human insulin. This can be achieved by recombinant DNA technology or chemical modification of pork insulin.⁴ Insulin is available as short-, intermediate-, or long-acting duration. The pharmacokinetics of available insulins is listed in Table 2.⁶

Some insulin can be mixed in the same syringe, but these mainly consist of the short- and intermediate-acting insulin. Insulin glargine, a long-acting formulation, should not be mixed with any other insulin due to its pharmacokinetic properties.⁷ Insulin glargine has been designed to have a low solubility at a neutral pH. After injection, the pH rises and leads to the formation of microprecipitates, causing a slow release of the insulin over 24 hours with no peak. If insulin glargine is mixed, it is likely the pH would be altered before entering the body. In addition, mixing insulin in the same syringe could likely contaminate the dose.

The maker of insulin glargine advises against mixing it with any other insulin.⁷ Several different studies have been done with admixtures of insulin glargine with short- or rapid-acting insulin. The studies revealed no differences in glycemic control, blunted and delayed rapid-acting insulin peak, the need for larger doses, or worsened glycemic control.^8-12

Other education points about insulin administration that are often overlooked or sometimes ignored by patients and that require follow-up for compliance include the following:

• Manufacturers recommend discarding an open bottle of insulin at room temperature after 28 days.⁷

• Insulin should be kept in a temperature-controlled environment between 36°F and 86°F.^4,7

• Rotation of injection sites is necessary to prevent lipodystrophy.^4,7

• It is recommended that patients stick with 1 approved anatomical site for all insulin injections, such as the abdomen or leg, to maintain consistent pharmacokinetics.^4,13,14

It is also important to know the constitution of the different insulins and whether they have been compromised. For example, if a clear solution insulin turns cloudy, it is considered compromised and should be thrown away.

CONCLUSION

Patients are diagnosed every day with diabetes, and many treatment regimens include insulin therapy. With the diagnosis of diabetes, patients are given extensive information on therapy, nutrition, preventative measures, and technique. Since controlling diabetes can call for intensive insulin therapy, medication administration instruction by HCPs is important. It is important to discuss in detail how the patient manages their insulin therapy at each visit so that issues will not be overlooked. Long-term, inappropriate use of insulin may lead to uncontrolled diabetes.

Diabetes is a complex disease to manage and takes a joint effort by both the HCP and patient to control. Patients need to understand the importance of compliance in all aspects of the disease, and the HCP needs to understand the importance of extensive counseling, including diet, exercise, and medication therapy. 

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Case

A 2-year-old girl was carried into the ED after falling off her bed earlier in the evening. The parents did not see the child fall, but heard her crying in her room. On physical examination, the patient was in a lot of pain, would not move her left arm, and had a left elbow effusion. The radial pulse was strong, and she was able to move all of her fingers but would not move her elbow. A lateral X-ray taken of the left elbow is shown below (Figure 1).  

Supracondylar Fractures

Supracondylar fractures are the most common pediatric elbow injury and disposition can range from outpatient follow-up to urgent surgical intervention. The average age of presentation is between 3 to 10 years, and the injury typically results from a fall on an outstretched hand (FOOSH) with hyperextension of the elbow. Supracondylar fractures may also occur after a direct blow to the elbow or hyperflexion.¹

The supracondylar area in children,  the distal portion of the humerus, is thin and weak. The force transmitted to this region by a direct blow or FOOSH injury can fracture the humerus. The brachial artery runs along the anterior humerus and can easily sustain injury. Median, ulnar, or radial nerve injuries are also common and can result in permanent disability.² Immediate neurovascular examination is mandatory, and diminished or absent pulses, poor perfusion, and pallor are signs of ischemia. Examination should include assessment of the radial pulse and the sensory and motor function of the median, radial, and ulnar nerves.  To test the median nerve (via the anterior interosseous branch), ask the patient make an “OK” sign with his or her fingers; to test the radial nerve, instruct the child to make a “thumb’s up” sign; and to test the ulnar nerve, have  the child hold his or her fingers spread-out against resistance. In addition, sensation of the palmer and dorsal surfaces and in between the fingers should be confirmed.

Plain radiographs, including anteroposterior (AP), oblique, and true lateral views, should be obtained. Interpretation of pediatric elbow films can be difficult, and the stages of ossification must be considered. The helpful acronym for remembering the order of bone ossification is CRITOE (capitellum, radial head, internal [medial] epicondyle, trochlea, olecranon, and external [lateral] epicondyle) (Table 1).

If the anterior humeral line—a line drawn through the anterior cortex of the humerus—fails to intersect the capitellum in its middle third, fracture of the distal humerus is present (Figure 2). The radial head should be aligned with the capitellum. Close inspection for a posterior fat pad, or “sail sign” is imperative as it indicates hemorrhage, joint effusion, or occult fracture. The presence of an anterior fat pad can be a normal variant; however, if the pad is wide and creates a “sail sign” then fracture must be assumed.¹

Fracture Types

Type III supracondylar fractures are completely displaced with a fracture through the anterior and posterior cortex. Since a high-risk of injury to the upper extremity vessels and nerves is associated with these very unstable fractures, routine neurovascular checks (while awaiting operative repair) are required. Supracondylar fractures are often associated with forearm or distal radius fractures; therefore, forearm radiographs should also be obtained.³

Diskitis

Tumors

Spondylolysis

Pediatric Cervical Spine Clearance

Thankfully, cervical spine injuries are rare, occurring in approximately 1% of children after blunt trauma.⁹ Left unrecognized, however, these injuries may result in permanent neurological disability. Children younger than 8 years of age are more likely to injure the upper cervical spine (C1 to C3) than older children and adults. This is because children have relatively larger heads than bodies and weaker cervical muscles and ligaments, making the upper cervical spine more mobile. The Emergency X-Radiography Utilization Study (NEXUS) criteria have been validated in adults; however, criteria for clearing the pediatric cervical spine are poorly studied. Because of limited data, there are few evidence-based guidelines for the clearance of the pediatric cervical spine. A study in 2001 found that the NEXUS guidelines where helpful in reducing imaging in 20% of children, but due to the low numbers of infants in this study, caution is advised when applying the NEXUS criteria to children under 2 years of age.⁹

Nonaccidental Trauma: Abuse

Orthopedic injury due to nonaccidental trauma (NAT) can be difficult to distinguish from normal childhood injuries. Identification of high-risk presentations is key in diagnosing these injuries and hopefully preventing further abuse. Femur fractures in children younger than age 1 year have a high likelihood of being nonaccidental, with between 60% to 80% of femoral shaft fractures resulting from abuse. No particular pattern of fracture is pathognomonic for NAT. The American Academy of Orthopaedic Surgeons recommends that children younger than age 36 months with a diaphyseal femur fracture be evaluated for child abuse.¹²

Spiral fractures and transverse fractures of long bones also raise suspicion for NAT. Injury to the metaphysis of long bones, especially in nonambulatory children, is considered highly suggestive of child abuse. The classic metaphyseal lesion, called a “corner” or “bucket-handle” fracture, occurs when the extremity (usually the forearm) is pulled or twisted forcibly, or the child is shaken. X-ray will demonstrate a disruption of the metaphysis with lucency. As the developing ribs are flexible and difficult to break with minor injuries, a child with a rib fracture and no history of severe trauma, such as a motor vehicle crash or fall from a significant height, has a high likelihood of being a victim of child abuse. Skull fractures caused from accidental injury and abuse may have similar presentations. The history and mechanism are important to correlate with physical examination findings for potential inconsistencies.¹³

Case Conclusion

The child in this case sustained a type II supracondylar fracture. Orthopedic surgery was consulted, and the patient was taken to the operating room for closed reduction and percutaneous pinning. She was placed in a cast, and pins were removed at follow-up 4 weeks later. No residual pain or deficits remained, and she regained full function of her arm.

Dr Hewett is a pediatric emergency medicine fellow, College of Medicine, Medical University of South Carolina, Charleston.
Dr Titus is vice chair, pediatric fellowships, and fellowship director, pediatric emergency medicine; and an associate professor of pediatrics, Medical University of South Carolina, Charleston.

Case

A 2-year-old girl was carried into the ED after falling off her bed earlier in the evening. The parents did not see the child fall, but heard her crying in her room. On physical examination, the patient was in a lot of pain, would not move her left arm, and had a left elbow effusion. The radial pulse was strong, and she was able to move all of her fingers but would not move her elbow. A lateral X-ray taken of the left elbow is shown below (Figure 1).  

Supracondylar Fractures

Supracondylar fractures are the most common pediatric elbow injury and disposition can range from outpatient follow-up to urgent surgical intervention. The average age of presentation is between 3 to 10 years, and the injury typically results from a fall on an outstretched hand (FOOSH) with hyperextension of the elbow. Supracondylar fractures may also occur after a direct blow to the elbow or hyperflexion.¹

The supracondylar area in children,  the distal portion of the humerus, is thin and weak. The force transmitted to this region by a direct blow or FOOSH injury can fracture the humerus. The brachial artery runs along the anterior humerus and can easily sustain injury. Median, ulnar, or radial nerve injuries are also common and can result in permanent disability.² Immediate neurovascular examination is mandatory, and diminished or absent pulses, poor perfusion, and pallor are signs of ischemia. Examination should include assessment of the radial pulse and the sensory and motor function of the median, radial, and ulnar nerves.  To test the median nerve (via the anterior interosseous branch), ask the patient make an “OK” sign with his or her fingers; to test the radial nerve, instruct the child to make a “thumb’s up” sign; and to test the ulnar nerve, have  the child hold his or her fingers spread-out against resistance. In addition, sensation of the palmer and dorsal surfaces and in between the fingers should be confirmed.

Plain radiographs, including anteroposterior (AP), oblique, and true lateral views, should be obtained. Interpretation of pediatric elbow films can be difficult, and the stages of ossification must be considered. The helpful acronym for remembering the order of bone ossification is CRITOE (capitellum, radial head, internal [medial] epicondyle, trochlea, olecranon, and external [lateral] epicondyle) (Table 1).

If the anterior humeral line—a line drawn through the anterior cortex of the humerus—fails to intersect the capitellum in its middle third, fracture of the distal humerus is present (Figure 2). The radial head should be aligned with the capitellum. Close inspection for a posterior fat pad, or “sail sign” is imperative as it indicates hemorrhage, joint effusion, or occult fracture. The presence of an anterior fat pad can be a normal variant; however, if the pad is wide and creates a “sail sign” then fracture must be assumed.¹

Fracture Types

Type III supracondylar fractures are completely displaced with a fracture through the anterior and posterior cortex. Since a high-risk of injury to the upper extremity vessels and nerves is associated with these very unstable fractures, routine neurovascular checks (while awaiting operative repair) are required. Supracondylar fractures are often associated with forearm or distal radius fractures; therefore, forearm radiographs should also be obtained.³

Diskitis

Tumors

Spondylolysis

Pediatric Cervical Spine Clearance

Thankfully, cervical spine injuries are rare, occurring in approximately 1% of children after blunt trauma.⁹ Left unrecognized, however, these injuries may result in permanent neurological disability. Children younger than 8 years of age are more likely to injure the upper cervical spine (C1 to C3) than older children and adults. This is because children have relatively larger heads than bodies and weaker cervical muscles and ligaments, making the upper cervical spine more mobile. The Emergency X-Radiography Utilization Study (NEXUS) criteria have been validated in adults; however, criteria for clearing the pediatric cervical spine are poorly studied. Because of limited data, there are few evidence-based guidelines for the clearance of the pediatric cervical spine. A study in 2001 found that the NEXUS guidelines where helpful in reducing imaging in 20% of children, but due to the low numbers of infants in this study, caution is advised when applying the NEXUS criteria to children under 2 years of age.⁹

Nonaccidental Trauma: Abuse

Orthopedic injury due to nonaccidental trauma (NAT) can be difficult to distinguish from normal childhood injuries. Identification of high-risk presentations is key in diagnosing these injuries and hopefully preventing further abuse. Femur fractures in children younger than age 1 year have a high likelihood of being nonaccidental, with between 60% to 80% of femoral shaft fractures resulting from abuse. No particular pattern of fracture is pathognomonic for NAT. The American Academy of Orthopaedic Surgeons recommends that children younger than age 36 months with a diaphyseal femur fracture be evaluated for child abuse.¹²

Spiral fractures and transverse fractures of long bones also raise suspicion for NAT. Injury to the metaphysis of long bones, especially in nonambulatory children, is considered highly suggestive of child abuse. The classic metaphyseal lesion, called a “corner” or “bucket-handle” fracture, occurs when the extremity (usually the forearm) is pulled or twisted forcibly, or the child is shaken. X-ray will demonstrate a disruption of the metaphysis with lucency. As the developing ribs are flexible and difficult to break with minor injuries, a child with a rib fracture and no history of severe trauma, such as a motor vehicle crash or fall from a significant height, has a high likelihood of being a victim of child abuse. Skull fractures caused from accidental injury and abuse may have similar presentations. The history and mechanism are important to correlate with physical examination findings for potential inconsistencies.¹³

Case Conclusion

The child in this case sustained a type II supracondylar fracture. Orthopedic surgery was consulted, and the patient was taken to the operating room for closed reduction and percutaneous pinning. She was placed in a cast, and pins were removed at follow-up 4 weeks later. No residual pain or deficits remained, and she regained full function of her arm.

Dr Hewett is a pediatric emergency medicine fellow, College of Medicine, Medical University of South Carolina, Charleston.
Dr Titus is vice chair, pediatric fellowships, and fellowship director, pediatric emergency medicine; and an associate professor of pediatrics, Medical University of South Carolina, Charleston.

Case

A 2-year-old girl was carried into the ED after falling off her bed earlier in the evening. The parents did not see the child fall, but heard her crying in her room. On physical examination, the patient was in a lot of pain, would not move her left arm, and had a left elbow effusion. The radial pulse was strong, and she was able to move all of her fingers but would not move her elbow. A lateral X-ray taken of the left elbow is shown below (Figure 1).  

Supracondylar Fractures

Supracondylar fractures are the most common pediatric elbow injury and disposition can range from outpatient follow-up to urgent surgical intervention. The average age of presentation is between 3 to 10 years, and the injury typically results from a fall on an outstretched hand (FOOSH) with hyperextension of the elbow. Supracondylar fractures may also occur after a direct blow to the elbow or hyperflexion.¹

The supracondylar area in children,  the distal portion of the humerus, is thin and weak. The force transmitted to this region by a direct blow or FOOSH injury can fracture the humerus. The brachial artery runs along the anterior humerus and can easily sustain injury. Median, ulnar, or radial nerve injuries are also common and can result in permanent disability.² Immediate neurovascular examination is mandatory, and diminished or absent pulses, poor perfusion, and pallor are signs of ischemia. Examination should include assessment of the radial pulse and the sensory and motor function of the median, radial, and ulnar nerves.  To test the median nerve (via the anterior interosseous branch), ask the patient make an “OK” sign with his or her fingers; to test the radial nerve, instruct the child to make a “thumb’s up” sign; and to test the ulnar nerve, have  the child hold his or her fingers spread-out against resistance. In addition, sensation of the palmer and dorsal surfaces and in between the fingers should be confirmed.

Plain radiographs, including anteroposterior (AP), oblique, and true lateral views, should be obtained. Interpretation of pediatric elbow films can be difficult, and the stages of ossification must be considered. The helpful acronym for remembering the order of bone ossification is CRITOE (capitellum, radial head, internal [medial] epicondyle, trochlea, olecranon, and external [lateral] epicondyle) (Table 1).

If the anterior humeral line—a line drawn through the anterior cortex of the humerus—fails to intersect the capitellum in its middle third, fracture of the distal humerus is present (Figure 2). The radial head should be aligned with the capitellum. Close inspection for a posterior fat pad, or “sail sign” is imperative as it indicates hemorrhage, joint effusion, or occult fracture. The presence of an anterior fat pad can be a normal variant; however, if the pad is wide and creates a “sail sign” then fracture must be assumed.¹

Fracture Types

Type III supracondylar fractures are completely displaced with a fracture through the anterior and posterior cortex. Since a high-risk of injury to the upper extremity vessels and nerves is associated with these very unstable fractures, routine neurovascular checks (while awaiting operative repair) are required. Supracondylar fractures are often associated with forearm or distal radius fractures; therefore, forearm radiographs should also be obtained.³

Diskitis

Tumors

Spondylolysis

Pediatric Cervical Spine Clearance

Thankfully, cervical spine injuries are rare, occurring in approximately 1% of children after blunt trauma.⁹ Left unrecognized, however, these injuries may result in permanent neurological disability. Children younger than 8 years of age are more likely to injure the upper cervical spine (C1 to C3) than older children and adults. This is because children have relatively larger heads than bodies and weaker cervical muscles and ligaments, making the upper cervical spine more mobile. The Emergency X-Radiography Utilization Study (NEXUS) criteria have been validated in adults; however, criteria for clearing the pediatric cervical spine are poorly studied. Because of limited data, there are few evidence-based guidelines for the clearance of the pediatric cervical spine. A study in 2001 found that the NEXUS guidelines where helpful in reducing imaging in 20% of children, but due to the low numbers of infants in this study, caution is advised when applying the NEXUS criteria to children under 2 years of age.⁹

Nonaccidental Trauma: Abuse

Orthopedic injury due to nonaccidental trauma (NAT) can be difficult to distinguish from normal childhood injuries. Identification of high-risk presentations is key in diagnosing these injuries and hopefully preventing further abuse. Femur fractures in children younger than age 1 year have a high likelihood of being nonaccidental, with between 60% to 80% of femoral shaft fractures resulting from abuse. No particular pattern of fracture is pathognomonic for NAT. The American Academy of Orthopaedic Surgeons recommends that children younger than age 36 months with a diaphyseal femur fracture be evaluated for child abuse.¹²

Spiral fractures and transverse fractures of long bones also raise suspicion for NAT. Injury to the metaphysis of long bones, especially in nonambulatory children, is considered highly suggestive of child abuse. The classic metaphyseal lesion, called a “corner” or “bucket-handle” fracture, occurs when the extremity (usually the forearm) is pulled or twisted forcibly, or the child is shaken. X-ray will demonstrate a disruption of the metaphysis with lucency. As the developing ribs are flexible and difficult to break with minor injuries, a child with a rib fracture and no history of severe trauma, such as a motor vehicle crash or fall from a significant height, has a high likelihood of being a victim of child abuse. Skull fractures caused from accidental injury and abuse may have similar presentations. The history and mechanism are important to correlate with physical examination findings for potential inconsistencies.¹³

Case Conclusion

The child in this case sustained a type II supracondylar fracture. Orthopedic surgery was consulted, and the patient was taken to the operating room for closed reduction and percutaneous pinning. She was placed in a cast, and pins were removed at follow-up 4 weeks later. No residual pain or deficits remained, and she regained full function of her arm.

Dr Hewett is a pediatric emergency medicine fellow, College of Medicine, Medical University of South Carolina, Charleston.
Dr Titus is vice chair, pediatric fellowships, and fellowship director, pediatric emergency medicine; and an associate professor of pediatrics, Medical University of South Carolina, Charleston.