Pulmonary thromboembolism after carbon monoxide poisoning

Accepted Manuscript Pulmonary thromboembolism after carbon monoxide poisoning: A case series and review of the literature

Yoonje Lee, Tae Ho Lim, Hyunggoo Kang, Jaehoon Oh, Byuk Sung Ko PII: DOI: Reference:

S0735-6757(18)30443-1 doi:10.1016/j.ajem.2018.05.063 YAJEM 57565

To appear in:

American Journal of Emergency Medicine

Received date: Accepted date:

23 May 2018 29 May 2018

Please cite this article as: Yoonje Lee, Tae Ho Lim, Hyunggoo Kang, Jaehoon Oh, Byuk Sung Ko , Pulmonary thromboembolism after carbon monoxide poisoning: A case series and review of the literature. Yajem (2017), doi:10.1016/j.ajem.2018.05.063

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Case report Pulmonary thromboembolism after carbon monoxide poisoning: A case series and review of the literature Short running title: Pulmonary thromboembolism with carbon monoxide

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Yoonje Lee, MD; Tae Ho Lim, MD, PhD; Hyunggoo Kang, MD, PhD; Jaehoon Oh, MD, PhD; Byuk

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Sung Ko, MD, PhD

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Department of Emergency Medicine, College of Medicine, Hanyang University, Seoul, Korea.

CORRESPONDENCE TO: Byuk Sung Ko, MD, PhD

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E-mail: [email protected]

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Seongdong-gu, Seoul 133-791, Korea

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Department of Emergency Medicine, College of Medicine, Hanyang University, 222 Wangsimni-ro

Author contributions: YL and BSK wrote the article. YL and BSK conceived the idea. HK and JO

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collected data. THL and HK conducted a critical review and supervised the whole study process. Ethics approval and consent to participate: The institutional review board of each institution

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approved the study and waived informed consent. Competing interests: The authors declare that they have no competing interests. Funding: This study was not financed. Acknowledgements: No acknowledgements to declare. Data availability statement: The data that support the findings of this study are available on request from the corresponding author, BS Ko. The data are not publicly available due to restrictions their containing information that could compromise the privacy of research participants.

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ABBREVIATIONS LIST CO = carbon monoxide; CPC = cerebral performance category; DVT = deep vein thrombosis; HBOT = hyperbaric oxygen treatment; LMWH = low-molecular-weight heparin; NOAC = new oral

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anticoagulant; PTE = pulmonary thromboembolism; CO hemoglobin = COHb

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ABSTRACT Objective: Carbon monoxide (CO) poisoning is known to increase thrombotic tendency, and the risk of deep vein thrombosis in individuals who have experienced CO poisoning is higher than in the

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general population. However, there are a few reports describing cases of pulmonary

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thromboembolisms (PTE) secondary to CO poisoning.

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Data Sources: Retrospective data analysis.

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Study Selection: Seven hundred fifty bed tertiary university affiliated hospital. Data Extraction and synthesis: Five patients with PTE after CO poisoning were observed. Two

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patients experienced cardiac arrest; they were treated successfully with tissue plasminogen activators and targeted temperature management. Their cerebral performance scores at discharge were both 1.

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Three patients had PTE and were treated with anticoagulation.

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Conclusions: To date, the causal relationship between PTE and CO poisoning is unclear. However, PTE should be considered in patients with CO poisoning as a differential diagnosis when unexplained

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are warranted.

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hypoxemia or shock are observed. Further studies on the association between CO poisoning and PTE

Key Words: carbon monoxide poisoning; pulmonary thromboembolism

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Introduction Carbon monoxide (CO) poisoning has been associated with thrombotic tendency; previous reports have described thrombosis in various organs.1-3 Cerebral, cardiac, mesenteric, and deep vein

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thrombosis (DVT) are associated with CO poisoning.4 One nationwide cohort study demonstrated that the risk of DVT is significantly higher in patients with CO poisoning.5 However, the association

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between CO poisoning and pulmonary thromboembolism (PTE) was not clear in that study.

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Furthermore, few reports about PTE exist to date. We present 5 cases of PTE in patients treated for

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CO poisoning.

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CASE 1

A 23-year-old woman was transferred from another hospital for CO poisoning. She had attempted to

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commit suicide by ingesting burning charcoal with alcohol. She had major depressive disorder and

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obesity. She responded to verbal commands. Her initial systolic blood pressure, diastolic blood pressure were 122 mmHg and 83 mmHg, respectively (Table 1). Her CO hemoglobin (COHb) level at

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first visited hospital could not be obtained. Her COHb level in our hospital was 2.9%. She was admitted to the general ward and was planned to receive hyperbaric oxygen treatment (HBOT).

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Eighteen hours after admission, she was collapsed in toilet and cardiac arrest occurred. Echocardiography showed a D-shaped left ventricle and dilatation of the right ventricle (Figure 1). She was successfully treated with intravenous tissue plasminogen activators and targeted temperature treatment. A PTE in the right pulmonary artery was observed using computed tomography (CT) (Figure 2). Low-molecular-weight heparin (LMWH) was administered and it was switched to new oral anticoagulants (NOAC). Her cerebral performance category (CPC) score at discharge was 1. CASE 2

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A 52-year-old woman was transferred from another hospital for intentional CO poisoning with charcoal burning and drugs. She did not have any chronic disease. Her COHb level at first visited hospital was 23.1% (Table 1). Her COHb level in our hospital was 7.9%. She was admitted to the general ward and received 3 courses of HBOT in 2.5 atmospheres absolute. Sixty-two hours after admission, cardiac arrest occurred. Right ventricle dilation and pulmonary hypertension on

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echocardiography was observed (Figure 3). A PTE in the left inferior pulmonary artery was observed

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using CT (Figure 4). The same treatment as that administered in case 1 was administered and her CPC

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score at discharge was 1. CASE 3

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A 48-year-old man was transferred from another hospital for intentional CO poisoning with charcoal burning and drugs. He did not have any comorbidities. His COHb level at first visited hospital was

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50.0% (Table 1). His COHb level in our hospital was 8.6%. He was admitted to the general ward and was planned to receive HBOT. Ten hours after admission, he had dyspnea and hypoxemia. His d-

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dimer levels were 1.32 mg/L and cardiac enzyme levels were also elevated (Table 1). PTE in the right

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upper and middle lobar arteries were observed using CT. Echocardiography did not show evidence of

CASE 4

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pulmonary hypertension. LMWH and NOAC were administered and his hypoxemia improved.

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A 63-year-old man was accidentally exposed to burning charcoal gas and intubated for comatose mentality. He had no chronic disease. His COHb level at first visited hospital was 6.8% (Table 1). His COHb level in our hospital was 0.9%. He had fever and elevated C-reactive protein levels, and chest CT was conducted to identify aspiration pneumonia. PTE in both pulmonary arteries were observed on chest CT incidentally. He could not complain of dyspnea or chest discomfort because of decreased mentality. No hypoxemia was observed. Echocardiography did not show evidence of pulmonary hypertension. LMWH and NOAC were administered and the extent of the PTE decreased on followup CT.

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CASE 5 A 46-year-old woman was transferred from another hospital for intentional CO poisoning with charcoal burning. She had major depressive disorder. Her COHb level at first visited hospital was 9.0% (Table 1). Her COHb level in our hospital was 1.6%. Twelve hours after admission, she had

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hypoxemia and tachypnea. Her d-dimer levels were 3.20 mg/L and tropoin I levels was 3.698 ng/mL (Table 1). PTE in the both interlobar arteries were observed using CT. Echocardiography did not show

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evidence of pulmonary hypertension. LMWH and NOAC were administered and her hypoxemia

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improved.

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DISCUSSION

To the best of our knowledge, this case series is the first describing PTE associated with CO

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poisoning. The patients in our study (except for 1 obese patient) had none of the conditions commonly associated with PTE, including recent surgery, trauma, active cancer, hormone therapy,

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immobilization, or heavy smoking. Episodes of PTE might be secondary to CO poisoning and

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massive PTE; even cardiac arrest can be observed in patients with CO poisoning. CO poisoning is known to be associated with more cardiovascular morbidity and mortality than in control populations based on epidemiology studies.6,7 The main mechanisms of cardiovascular disease

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by CO poisoning are hypoxia and atherosclerosis.8 Accumulation of cholesterol in the coronary artery

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and endothelial damage was shown in several animal studies.9,10 CO poisoning is also known to cause inflammation and hypoxia, which could induce endothelial injury and hypercoagulability.5 With respect to venous thrombosis, CO has been found to induce thrombus formation through bloodstream stasis, increasing vascular permeability, leading to platelet dysfunction and polycythemia.1 Chung et. al. demonstrated that CO poisoning was associated with a 3.85-fold higher risk of DVT than in a control group without CO poisoning.5 However, the association with PTE was not significant after adjusting for confounding variables. They explained that CO causes hypoxia and inflammation by increasing levels of oxygenase-1 protein, and releasing myeloperoxidase and

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reactive oxygen species, which lead to oxidative stress. Venous thrombosis has been reported to be associated with inflammation and oxidative stress. One 22-year-old man was treated for CO poisoning and DVT was detected.11 One PTE with CO poisoning has been reported in a 70-year-old man.12 To date, we could not find reports of massive embolisms, which even result in cardiac arrest.

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Physicians should consider PTE and DVT as differential diagnoses when there are unexplained dyspnea, hypoxemia, or shock in patients with CO poisoning. However, the association between CO

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poisoning and PTE remains unclear; hence, further investigation is warranted.

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1.

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References

Grace TW, Platt FW. Subacute carbon monoxide poisoning. Another great imitator. JAMA.

2.

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1981;246(15):1698-1700.

Nielsen VG, Hafner DT, Steinbrenner EB. Tobacco smoke-induced hypercoagulation in human plasma: role of carbon monoxide. Blood Coagul Fibrinolysis. 2013;24(4):405-410. Aronow WS.

Effect

of

carbon

monoxide on

1979;8(3):271-278. 4.

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3.

cardiovascular

Prev Med.

disease.

Teodoro T, Geraldes R, Pinho e Melo T. Symptomatic internal carotid artery thrombosis in

5.

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acute carbon monoxide intoxication. Am J Emerg Med. 2014;32(6):684 e685-686. Chung WS, Lin CL, Kao CH. Carbon monoxide poisoning and risk of deep vein thrombosis and pulmonary embolism: a nationwide retrospective cohort study. J Epidemiol Koskela RS. Cardiovascular diseases among foundry workers exposed to carbon monoxide.

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6.

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Community Health. 2015;69(6):557-562. Scand J Work Environ Health. 1994;20(4):286-293. 7.

Stern FB, Lemen RA, Curtis RA. Exposure of motor vehicle examiners to carbon monoxide: a historical prospective mortality study. Arch Environ Health. 1981;36(2):59-65. Zevin S, Saunders S, Gourlay SG, Jacob P, Benowitz NL. Cardiovascular effects of carbon

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monoxide and cigarette smoking. J Am Coll Cardiol. 2001;38(6):1633-1638. 9.

Astrup P, Kjeldsen K, Wanstrup J. Effects of carbon monoxide exposure on the arterial walls.

10.

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Ann N Y Acad Sci. 1970;174(1):294-300. Chen YG, Lin TY, Dai MS, et al. Risk of Peripheral Artery Disease in Patients With Carbon Monoxide Poisoning: A Population-Based Retrospective Cohort Study. Medicine (Baltimore). 2015;94(40):e1608. 11.

De Matteis G, Fuorlo M, Montalto M, Landolfi R. Screening for and prophylaxis of venous thromboembolism

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monoxide

poisoning?

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2015;33(4):592-593. 12.

Sevinc A, Savli H, Atmaca H. An interesting cause of pulmonary emboli: acute carbon monoxide poisoning. Clin Appl Thromb Hemost. 2005;11(3):353-357.

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Figure Legends

Fig. 1 Echocardiography in case 1. Echocardiography shows D-shaped LV and right ventricle

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dilatation. LV, left ventricle.

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pulmonary artery. CT, computed tomography.

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Fig. 2 Pulmonary embolism CT in case 1. A pulmonary thromboembolism is observed in the right

Fig. 3 Echocardiography in case 2. Right ventricle dilation and pulmonary hypertension is observed.

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Fig. 4 Pulmonary embolism CT in case 2. A pulmonary thromboembolism is observed in the left

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inferior pulmonary artery. CT, computed tomography.럏

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TABLE 1. Patient Characteristics

Characteristics

Patient No.

2

3

4

5

Age (years)

23

52

48

63

46

Sex

Female

Female

Male

Comorbidities

MDD, obesity

None

None

Cigarette-

No

No

Yes

Yes

Yes

Yes

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No

Yes

Yes

Yes

Yes

Yes

Yes

No

No

No

No

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No

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No

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Normobaric

Female

MDD

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another hospital

Male

None

smoking

Transferred from

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1

Propranolol,

administered

Zanapam

Initial vital signs

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Medication

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oxygen applied

SBP (mmHg)

122

101

143

119

106

DBP (mmHg)

83

54

78

86

70

HR (beats/min)

92

75

100

84

86

RR (breaths/min)

18

20

20

24

18

BT (°C)

36.5

34.8

36.8

38.1

36.5

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Blood oxygen

100

99

100

100

99

Verbal

Painful

Alert

Unresponsive

Verbal

Not checked

23.1

50.0

13,100

6,000

13,700

14.0

11.5

216,000

235,000

saturation (%)

Mental status

Laboratory

19,100

16.0

10.0

14.4

226,000

133,000

333,000

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(g/dL)

Platelet

9.0

8,300

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Hemoglobin

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(counts/mm3)

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hemoglobin (%)

WBC

6.8

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Initial CO

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findings

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(counts/mm3)

1.87

0.24

1.32

6.86

3.20

CK (U/L)

363

86

8257

5994

31649

4.3

0.9

43.6

6.2

300

0.279

0.01

2.398

0.076

3.698

93

16

80

81

315

24

62

10

48

12

(ng/mL)

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CK-MB

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D-dimer (mg/L)

Troponin-I (ng/mL)

BNP (pg/mL)

Other features

CO exposure to

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PTE (h)

PTE before

No

Yes, 3 times

No

No

Yes

Cardiac arrest

Yes

Yes

No

no

No

Treatment

tPA

tPA

Anticoagulation

Anticoagulation

Anticoagulation

Anticoagulation

Anticoagulation

TTM

TTM

No test

No DVT

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DVT

No test

Right upper

Both pulmonary

Both interlobar

middle lobe

artery

artery

Sinus rhythm

Sinus rhythm

pulmonary

pulmonary

artery

artery

lobar artery

Sinus

Sinus rhythm

Sinus

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Left inferior

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tachycardia

tachycardia

Pulmonary

Pulmonary

No pulmonary

No pulmonary

No pulmonary

hypertension

hypertension

hypertension

hypertension

hypertension

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Echocardiography

No test

Right

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ECG

Lt. tibial vein

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(after tPA)

Site of PTE

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HBOT

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BNP = B-type natriuretic peptide; BT = body temperature; CK = creatine kinase; CK-MB = creatine kinase-muscle/brain; CO = carbon monoxide; DBP = diastolic blood pressure; DVT = deep vein thrombosis; ECG = electrocardiogram; HBOT = hyperbaric oxygen treatment; HR = heart rate; MDD = major depressive disorder; PTE = pulmonary thromboembolism; RR = respiratory rate; SBP =

systolic blood pressure; tPA = tissue plasminogen activator; TTM = targeted temperature management.

Figure 1

Figure 2

Figure 3

Figure 4