Triple Air Leak Syndrome in Cannabinoid Hyperemesis: A Diagnostic Challenge Managed Conservatively

INTRODUCTION

Cannabinoid hyperemesis syndrome (CHS) is known to cause cyclic episodes of nausea, vomiting, and abdominal pain in chronic cannabis users.¹ Existing literature highlights that CHS can lead to rare complications, including spontaneous pneumomediastinum (SPM), and Boerhaave syndrome (BS).^2,3 However, the sudden and forceful vomiting can also lead to the rare occurrence of spontaneous pneumopericardium (SPP) and pneumoretroperitoneum (SPR).^4,5 Shared clinical features of SPM, BS, SPP, and SPR, make distinguishing them in acute CHS challenging.^2,3 These atypical presentations may result in misdiagnosis or delayed recognition, particularly in patients with a history of illicit drug use. BS usually requires surgical intervention, whereas SPP, SPR and SPM resolve conservatively if uncomplicated.^2,3,5

We present a unique case of a young woman with CHS who developed a rare combination of triple air leaks involving the pericardium, mediastinum, and retroperitoneum, all of which resolved with conservative management. This combination is exceptionally uncommon, highlighting the need for more case reports to enhance clinical awareness and management, ultimately reducing morbidity and mortality.⁵

CASE REPORT

A 21-year-old woman with a history of chronic cannabis use presented to the emergency department with a 24-hour history of sharp, nonradiating, epigastric pain rated 10/10. The pain was associated with persistent nausea and repeated episodes of nonbloody, nonbilious vomiting. She denied recent fatty food intake, trauma, fever, diarrhea, constipation, and alcohol use. Last cannabis use was 3 days prior.

She smoked marijuana 4–5 times daily for 2–3 years with multiple prior CHS hospitalizations managed conservatively.

On arrival, vitals and laboratory results are shown in Tables 1 and 2. She appeared visibly uncomfortable. Chest examination revealed palpable crepitus at the neck base and anterior chest wall. Abdominal examination showed a soft, diffusely tender abdomen. Ethanol level was <10 mg/dL. Urine drug screen was positive for cannabinoids and negative for opiates, cocaine, and benzodiazepine. Urinalysis showed leukocytes 2+, white blood cells (WBC) >25, blood 3+, red blood cells >20, nitrite negative. Blood and urine cultures were negative.

Initial chest X-ray (CXR) revealed pneumomediastinum with air tracking along the bilateral neck base and chest wall as shown in Figure 1. Computed tomography scan of the chest, abdomen, and pelvis with intravenous and oral contrast confirmed extensive pneumomediastinum, predominantly on the left side of the chest wall, pneumopericardium, and retroperitoneal air surrounding the upper abdominal aorta as shown in Figure 2. These findings raised concerns for esophageal perforation. The patient was admitted to the intensive care unit for close monitoring and managed conservatively with nil per os, Intravenous Ringer lactate at 100 mL/h for 12 hours, pain medications, electrolytes replacement, antiemetics, and antibiotic piperacillin-tazobactam for 4 days due to leukocytosis, elevated lactate, and concern for urinary infection. She remained hemodynamically stable.

Given the pneumopericardium on CT chest, a transthoracic echocardiogram performed on day one was grossly normal, with no concerning acute findings. To further evaluate for esophageal perforation, a water-soluble contrast esophagogram was performed on hospital day 2 which showed normal esophageal peristalsis without contrast leak or perforation as shown in Figure 3. Given a negative work-up for esophageal perforation, BS was ruled out, and she was downgraded to regular medical floor.

Serial CXR demonstrated gradual improvement in pneumomediastinum as shown in the image (Figure 1). Over 4 days of hospitalization, she showed steady clinical improvement and tolerated oral intake. She was discharged in stable condition with instruction on cannabis cessation, enrolment in assistance programs, and outpatient close follow-up.

Patient was followed up periodically as outpatient for 1 year, she reported no recurrence of symptoms. Physical examination revealed complete resolution of crepitus, and no further imaging was performed. She has had no hospitalizations since discharge and remains actively engaged in cessation program.

DISCUSSION

The lack of direct trauma or fistula in CHS makes air leakage unusual.^6,7 The proposed mechanism involves a sudden increase in intra-alveolar pressure, often due to severe vomiting and retching, leading to alveolar rupture.² The precise pathway by which air enters the mediastinum, pericardial, and retroperitoneal spaces remain incompletely understood.^8,9

Our patient demonstrated recurrent leukocytosis (WBC >13 × 10⁹/L) during both the current and previous CHS episodes. Chronic cannabis use appears to lead to consistently elevated WBC, which may cause a low-grade inflammatory response, increasing tissue fragility and the risk of spontaneous air leaks from the alveolar walls into the pericardium, mediastinum, and retroperitoneum.¹⁰

Alongside these laboratory abnormalities, the patient also had an elevated lactic acid and urinalysis findings suggestive of urinary tract infection; the improvement of lactic acidosis following fluids and antibiotics supports a concurrent infection. This highlights the importance of considering alternative or coexisting causes for laboratory abnormalities in CHS.

In literature reviewing 24 cases, symptoms of SPM and SPP usually presented as chest pain and mild abdominal discomfort.^11,12 However, our case was unique, as we observed both conditions simultaneously along with air in the retroperitoneum, leading to acute abdominal pain. This emphasizes the need for increased awareness of such presentation with chronic cannabis use. Prompt imaging is essential for management. A CT scan should be prioritized in stable patients with significant intrapericardial air.^13,14 The hemodynamic consequences of pneumopericardium in CHS are still underexplored.

A similar case in the literature also reported successful conservative management. It is crucial to distinguish SPM from BS, as patients with the former are typically younger and well-appearing, unlike the toxic appearance often seen in BS, and misdiagnosis may lead to unnecessary diagnostic work-up.² In addition, some ongoing trials have shown that successful conservative management can be achieved through supportive care, prompt administration of antiemetics like haloperidol, and empirical antibiotics.^15,16

This case demonstrates that conservative management with close monitoring is effective in hemodynamically stable patients without cardiorespiratory compromise; surgical intervention is reserved for cases where conservative measures fail, or if the patient develops hemodynamic or cardiorespiratory instability, or a persistent air leak. It also underscores a critical knowledge gap in the understanding of CHS-associated air leak syndromes and the personalized approach to treatment. Randomized clinical trials are needed to compare clinical outcomes of conservative vs surgical management.

DISCLOSURES

Author contributions: K. Ali contributed to patient management, data collection, and critical review of the manuscript, including revisions to the initial draft. A. Masood Shah and A. Hyder was responsible for initial manuscript drafting and literature review. V. Balderas reviewed and approved the final manuscript. K. Ali is the article guarantor.

Financial disclosure: None to report.

Previous presentation: This case was presented at the ACG Annual Scientific Meeting; October 25–30, 2024; Philadelphia, Pennsylvania.

Informed consent was obtained for this case report.