Hiccups as Rare Presentation of Bilateral Pulmonary Embolism: Case Report

Abstract

Background:

Pulmonary embolism is considered a life-threatening condition, with a variable spectrum of clinical presentations. Dyspnea, hemoptysis, and chest pain are the classical symptoms; however, atypical presentations may delay the diagnosis. Persistent hiccups as the sole presentation of pulmonary embolism are rarely reported, posing a diagnostic challenge. Identifying this rare presentation is paramount for early diagnosis and improving patient outcomes.

Case Presentation:

A 76-year-old Egyptian man was admitted with persistent, daily hiccups lasting ~2 months, refractory to conservative and pharmacologic measures. He denied chest pain, dyspnea, or any respiratory or gastrointestinal symptoms. On admission, physical examination was unremarkable, while laboratory testing revealed an elevated D-dimer level. On hospital day 1, lower limb Doppler ultrasound demonstrated acute deep vein thrombosis in the right lower extremity. Subsequently, CT pulmonary angiography confirmed bilateral pulmonary embolism.

Conclusions:

This case highlights persistent hiccups as the sole manifestation of pulmonary embolism. Clinicians should maintain a high index of suspicion for pulmonary embolism in elderly patients presenting with persistent, unexplained hiccups particularly after common causes of hiccups have been excluded. Early diagnosis and timely treatment are crucial to reducing morbidity and improving patient outcomes in such atypical presentations.

Learning Points

1. Persistent unexplained hiccups can be rare presenting symptoms of pulmonary embolism.

2. Patients may present without the typical symptoms of pulmonary embolism.

3. Prompt recognition and imaging are essential.

Introduction

Pulmonary embolism is the third most common cause of cardiovascular syndromes, following myocardial infarction and stroke. ¹ Its annual incidence ranges from 39 to 115 cases/100 000 population. ² Acute pulmonary embolism can be life-threatening, making prompt diagnosis and timely initiation of anticoagulation therapy crucial. Patients with suspected pulmonary embolism typically present with symptoms such as dyspnea, chest pain, presyncope, or hemoptysis. ³ However, in some cases, pulmonary embolism may be asymptomatic or incidentally detected during imaging performed for other indications.

Hiccups occur result from involuntary, intermittent, spasmodic contractions of the diaphragm and intercostal muscles. The hiccup reflex arc consists of an afferent limb that includes the phrenic and vagus nerves, and an efferent limb, that is, primarily mediated by the phrenic nerve. Irritation of any part of this reflex arc can lead to hiccups. ⁴ While hiccups are usually self-limiting, persistent hiccups can significantly impair a patient’s quality of life. Prolonged hiccups can lead to malnutrition, dehydration, and weight loss due to interference with eating and drinking. ⁵ Additionally, they may exacerbate pain and cause insomnia. Most individuals experience hiccups lasting <48 hours, which typically resolve spontaneously within minutes. In contrast, persistent hiccups lasting longer than 48 hours are rare and may be associated with serious underlying conditions, including central nervous system disorders such as tumors, vascular malformations, infections, or multiple sclerosis. ⁴ Structural abnormalities within the thoracic region, such as enlarged lymph nodes due to neoplasms, aortic aneurysms, or mediastinal tumors, as well as chest infections like pneumonia or empyema, have also been linked to persistent hiccups. ⁴ Pulmonary embolism is a rare important cause of persistent hiccups.^6-10 While the exact mechanism by which pulmonary embolism causes hiccups remains unclear, it is hypothesized that it may result from irritation of the afferent or efferent limbs in the chest. ¹⁰ Herein, we report a case of bilateral pulmonary embolism presenting with persistent hiccups as the sole symptom.

Case Presentation

A 76-year-old male presented to our hospital with a 2-month history of persistent hiccups.

He described the hiccups as constant and unrelated to any specific activity or dietary changes that might trigger or relieve them. The patient had recently traveled to Egypt, where he experienced a brief episode of sudden shortness of breath. During his return flight to Doha, he noticed right lower limb swelling and slight tenderness. Upon arrival in Doha, he visited a primary healthcare center for post-travel COVID-19 screening and evaluation of his hiccups. He was prescribed medication, the name of which he does not recall. He was also advised to undergo blood tests after 1 week.

A few days later, he presented to the emergency department with complaints of gradually worsening swelling in his right leg along with persistent hiccups. Upon evaluation in the emergency department, he denied experiencing abdominal pain, chest pain, dyspnea, or neurological symptoms. He is a non-smoker and does not consume alcohol. His current medications included Mebeverine, Moxonidine, and a combination of amlodipine/valsartan. His significant past medical history included hypertension and benign prostatic hyperplasia.

On examination, the patient had a blood pressure of 145/79 mmHg, a heart rate of 63 beats/minute, and a respiratory rate of 17 breaths/minute. He exhibited intermittent hiccups, and his oxygen saturation was 99% on room air. The physical examination revealed a moderately built male in no apparent distress, though he was hiccupping continuously throughout the exam.

A thorough examination of the head, eyes, ears, nose, and throat (HEENT), as well as the pulmonary, cardiovascular, and neurological systems, was unremarkable. A portable chest radiograph showed no evidence of acute cardiopulmonary pathology. Additionally, evaluation for acute coronary syndrome was negative, with a normal electrocardiogram.

In the emergency department, the patient was found to have an elevated D-dimer level (8.71 mg/L FEU) and elevated creatinine (124 µmol/L). Inflammatory markers were raised, with a C-reactive protein of 70.6 mg/L. Cardiac biomarkers showed a troponin level of 19 ng/L. Other laboratory results showed a lactic acid level of 1.5 mmol/L, sodium 134 mmol/L, potassium 4.9 mmol/L, ALT 25 U/L, and AST 28 U/L. The patient was hemodynamically stable and did not require thrombolysis, critical care admission, supplemental oxygen, or inferior vena cava (IVC) filter placement. A thrombophilia and autoimmune workup, including protein C, protein S, anti-dsDNA, and antiphospholipid antibodies, was negative.

A Doppler ultrasound of the lower limb revealed a deep venous thrombosis (DVT) involving right popliteal vein extending to the proximal posterior tibial vein. The ECG showed normal sinus rhythm with no tachycardia or S1Q3T3 pattern and echocardiography was not performed. A CT pulmonary angiography was subsequently performed, which demonstrated filling defect noted at the bifurcations of the left pulmonary artery, segmental and subsegmental branches of the right and left pulmonary artery (Figure 1). The patient was immediately started on a therapeutic dose of enoxaparin, and by the following day, his hiccups had improved. Three days after the initiation of treatment, the hiccups had completely resolved.

Figure 1.

Two sections of computed tomography pulmonary angiogram showing filling defect noted at the bifurcations of the left pulmonary artery, segmental and subsegmental branches of the right and left pulmonary artery (arrows).

During his inpatient stay, the patient reported lower urinary tract symptoms. His prostate-specific antigen (PSA) level was elevated at 13.5 ng/mL (normal range: 0.00-4.00 ng/mL). Following a consultation with the urology team, a CT scan of the abdomen pelvis was performed, which showed significant prostate enlargement (Figures 2 and 3). A prostate biopsy was carried out due to suspicion of prostate cancer; however, the histopathology results revealed benign prostatic tissue.

Figure 2.

Computed tomography sections of the abdomen.

Figure 3.

Computed tomography sections showing huge prostates.

The patient was diagnosed with provoked pulmonary embolism due to recent travel. He was hospitalized for ~10 days and was discharged on apixaban 5 mg twice daily, with a planned treatment duration of 6 months. At a follow-up visit 2 months after discharge, conducted in our anticoagulation clinic, the patient reported complete resolution of his hiccups since being discharged.

Discussion

Persistent hiccups as the presenting symptom of an otherwise asymptomatic pulmonary embolism have been rarely documented in medical literature. Our review identified five case reports/series describing hiccups as the primary symptom of pulmonary embolism^6-10 (as summarized in Table 1). In one case, the patient was later diagnosed with non-small cell lung carcinoma and passed away 6 months after the initial presentation. ⁶ Another case involved a patient who had undergone elective surgery 5 days before the onset of hiccups, which persisted for 3 days before a diagnosis of pulmonary embolism was made. ⁷ A third case, closely resembling ours, described a pulmonary embolism presenting solely with hiccups as the primary symptom and no identifiable predisposing factors. ⁸ In such unusual presentations, typical symptoms of pulmonary embolism, such as dyspnea and pleuritic chest pain, are often absent. Persistent hiccups lasting more than 48 hours without a clear cause should prompt physicians to investigate potential underlying pathological conditions.

Table 1.

Summary of Reported Cases in Literature.

Author	Age (y)	Gender	Presenting symptom besides hiccups	Site of PE	DVT (Y/N)	PE unilateral vs bilateral	Provoked vs unprovoked	Anticoagulation at beginning	Anticoagulation at discharge	Duration till hiccups resolved (d)	Total duration of anticoagulation
Budhram et al 9	50	Male	none	NA	No	Bilateral	Unprovoked	Rivaroxaban	Rivaroxaban	1	NA
Durning et al 8	81	Male	none	Left lower lobe	No	unilateral	Unprovoked	Warfarin with Enoxaparin bridging	Warfarin	14	NA
Thind et al 7	60	Male	none	Right upper, right lower lobe	NA	unilateral	Provoked (recent surgery)	Enoxaparin	Apixaban	10	NA
Zylicz 6	58	Male	none	NA Inferior vena cava thrombosis	No	NA	Provoked (lung cancer)	Dalteparin	Dalteparin	2	3 wk
Worku Hassen et al 10	Patient 1, 52	male	Dyspnea, dry Cough, upper back pain increased with inspiration	Saddle embolus	No	Bilateral	Unprovoked	Heparin then thrombectomy	NA	NA	NA
	Patient 2, 40	female	Left lower back pain	Large left pulmonary artery embolus	No	Unilateral	Provoked (recent surgery)	Heparin infusion and Warfarin	Warfarin	NA	NA
	Patient 3, 46	Male	none	Left pulmonary artery embolus	No	Unilateral	Provoked (recent surgery)	NA	NA	NA	NA

Hiccups are defined as sudden, involuntary spasms of the diaphragm, resulting in rapid inhalation, that is, abruptly interrupted by the closure of the glottis. ¹¹ Numerous potential causes of hiccups have been described and can be broadly categorized as gastrointestinal, metabolic, postoperative, central nervous system-related, head and neck-related, thoracic, psychogenic, or idiopathic.

In our case, the only abnormal finding after an extensive evaluation was bilateral pulmonary embolism, with no evidence of any mass or other factors that could have triggered the hiccup reflex. Based on the imaging results, the patient was started on therapeutic enoxaparin. Two days later, his symptoms improved significantly, and the hiccups were no longer bothersome. He was subsequently discharged with a diagnosis of provoked pulmonary embolism related to recent travel and was prescribed apixaban 5 mg twice daily for a planned 6-month course of anticoagulation. At a follow-up visit 2 months after discharge in the anticoagulation clinic, the patient reported complete resolution of hiccups since his discharge.

Strengths and Limitations

This case adds to the limited number of cases published in the literature describing persistent hiccups as rare and isolated manifestation of pulmonary embolism. Furthermore, temporal association between initiation of anticoagulation therapy and resolution of symptoms supports the probable link between hiccups and pulmonary embolism. Moreover, the sustained resolution of the symptoms during follow up in the anticoagulation clinic supports both the diagnosis and management approach.

As it is a single case report, it lacks generalizability and does not establish causality, also there could be a coincidence between resolution of the symptoms along with starting and maintaining anticoagulation. Therefore, further cases would be essential to clarify and establish the relationship between hiccups and pulmonary embolism.

Conclusion

This case highlights the importance of including pulmonary embolism in the differential diagnosis of persistent hiccups, particularly when common causes have been excluded. Early recognition and appropriate management can lead to resolution of the symptoms and prevent serious complications, clinicians should be aware of this association to facilitate early diagnosis and improve patient outcomes.