Continuing Education Activity

Pneumatosis intestinalis can be classified as primary or secondary, but both are representative of underlying pathology. Pathophysiology and etiology depend on the underlying conditions, and prompt diagnosis is crucial in determining the treatment regimen. This activity reviews the evaluation and management of pneumatosis intestinalis and highlights the importance of an interprofessional team in managing patients with this condition.

Objectives:

• Describe the pathophysiology of pneumatosis intestinalis.
• Review the appropriate process for the evaluation of pneumatosis intestinalis.
• Outline the management options for pneumatosis intestinalis.
• Summarize the importance of collaboration amongst the interprofessional team to enhance the care of patients with pneumatosis intestinalis.

Introduction

The presence of gas and free air in the extraluminal space of the intestines is known as pneumatosis intestinalis (PI). The presence of air in any portion of the gastrointestinal tract, from the mucosa to the mesenteric vessels via diffuse collection, cysts, or bubbles, is an abnormal occurrence, correlating with underlying pathology. However, gas in the actual intestines is normal and usually relieved with flatulence.

In other medical literature, pneumatosis intestinalis is also referred to as pneumatosis cystoides intestinalis, intraluminal bowel gas, and pneumatosis coli, depending on where and how free air accumulates in the extraluminal space of the digestive tract. Pneumatosis cystoides intestinalis is a collection of individual gas cysts in the submucosa and subserosa of the intestine that can increase in quantity and size if left untreated. The occurrence was first documented in 1730 by DuVernoi during cadaver dissection. It was first diagnosed radiographically in 1946 by Lerner and Gazin, but the clinical pathology and etiology were unknown. Since then, the incidence of pneumatosis intestinalis has increased due to advancements in radiology.[1][2][3][4][5][6]

Etiology

Pneumatosis intestinalis itself is not a primary disease but a clinical sign of underlying pathology. In 1998, BL Pear proposed the mechanisms behind extraluminal gas formation included bowel necrosis, pulmonary disease, and abnormal mucosal permeability. The cause of PI may also be multifactorial from pulmonary, mechanical, and bacterial causes, although mucosal integrity disruption is present in all scenarios. The condition can also further be divided into primary and secondary types. In primary pneumatosis intestinalis, the gas collection is benign in nature and creates a cystic pattern in the intraluminal wall. Secondary pneumatosis intestinalis is correlated with a pathological condition, and gas distribution appears in a more linear fashion.[2][4][5][7]

Epidemiology

Pneumatosis intestinalis occurs in approximately 0.03% of the population. Given the asymptomatic course of the majority of cases, the exact prevalence of the condition is unknown, and that 0.03% is possibly an underestimation. It can affect any age group, although it is more prevalent in older populations than in young adults and infants. Infantile PI has higher mortality than adult forms, and it is usually associated with acute necrotizing enterocolitis. In adults, PI is usually benign and found incidentally on imaging. In adults, approximately 15% of cases are primary, and 85% are secondary.[5][7][8]

Pathophysiology

Gas distribution in the extraluminal space is a multifactorial process. There are three hypotheses of pathogenesis labeled mechanical, pulmonary, and bacterial theories. The mechanical theory hypothesizes that an increase in intraluminal pressure may lead to mucosal damage. Surgical complications and endoscopies can cause blunt trauma, forcing gas from the gastrointestinal cavity into extraluminal space. Gas transmits through the tissue layers and propagates via peristalsis. Lung diseases such as asthma, interstitial pneumonia, and chronic obstructive pulmonary disease can cause alveolar rupture that may release gas into the mesenteric vasculature. The pulmonary theory states that gas can propagate caudally into the retroperitoneum and mesentery from the mediastinum.

It is hypothesized that gas migrates through the mediastinal vessels into the mesentery. Finally, the bacterial theory states gas-producing bacteria such as Escherichia coli and Clostridia species can invade the intraluminal compartments, which is supported by the decrease in gas after antimicrobial drug therapy and proximity of the gas cysts near blood vessels. In neonates, pneumatosis intestinalis is usually a radiographic sign of necrotizing enterocolitis. Risk factors include prematurity, low birth weight, and formula diet.[3][4][6][8][9]

History and Physical

The clinical presentation may vary depending on whether a patient presents with primary or secondary pneumatosis intestinalis. Primary or benign causes usually result in mild abdominal symptoms. There are reported cases where patients with primary PI presented without symptoms. However, patients with secondary pneumatosis intestinalis may present with life-threatening peritoneal symptoms, similar to that of intestinal ischemia and peritonitis. Other symptoms of secondary PI include hematochezia, tenesmus, constipation, and abdominal pain. Approximately 3% of patients presenting with PI also reported complications such as pneumoperitoneum, intestinal ischemia, and obstruction. History of abdominal laparotomy and endoscopy can be common in patients as procedures leading to mucosal disruption, causing an increase in intraluminal pressure can lead to pneumatosis intestinalis. There are also many diseases and conditions in a patient’s history that are known to be associated with PI (via the three mechanisms), including but not limited to:[3][4][6][10]

• Pulmonary disease - Asthma, chronic obstructive pulmonary disease (COPD), emphysema 
• Autoimmune - Lupus variants, polymyositis, dermatomyositis, polyarteritis nodosa, celiac sprue
• Drug-induced - Glucosidase inhibitors, corticosteroids
• Gastrointestinal - Inflammatory bowel disease (IBD), diverticulitis, colitis, Clostridium difficile infection, appendicitis, carcinoma, peptic ulcer, perforation, necrotizing enterocolitis (pediatric)
• Infectious - Human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS), mycobacterium tuberculosis, 2019 novel coronavirus (COVID-19)
• Iatrogenic - Blunt abdominal trauma, endoscopy, post-surgical intestinal anastomosis, barium enema, positive end-expiratory pressure (PEEP) ventilation

Evaluation

Abdominal radiographs, computed tomography, magnetic resonance imaging, and ultrasonography are used to diagnose pneumatosis intestinalis. However, one-third of patients’ radiographs may not reveal any signs, such as thickened bowel walls containing gas. Computed tomography is the most sensitive imaging modality as it better distinguishes intraluminal air from submucosal fat and detects additional underlying causes of pneumatosis intestinalis such as portal air, colonic tissue stranding, and dilated bowel. Subsequent imaging should be performed to assess the presence and expansion of portal venous and intra-abdominal air.

Gas can be distributed in a cystic pattern as seen with pneumatosis cystoides intestinalis or linear, which is associated more with bowel ischemia and portal venous gas. A linear pattern is more in line with the secondary PI. Ling et al. reported that gas cysts can be located in the colon (46%), small intestines (27%), large intestines (7%), and stomach (5%). An endoscopy can be performed to characterize the distribution of gas formation (linear versus cystic) and to exclude any other colonic lesions. Laboratory tests play an important role in determining the treatment and management of benign versus life-threatening cases. Such laboratory exams include but are not limited to white blood cell count, lactic acid, aspartate aminotransferase, alanine aminotransferase, amylase, bicarbonate level, and alkaline phosphatase.[3][6][10][11]

Treatment / Management

There are differences in treatment options between primary and secondary pneumatosis intestinalis. Other factors influencing treatment include laboratory values and clinical presentation of the patient. Since PI is not a disease in itself but a clinical sign, treatment begins with the underlying cause. A conservative, non-surgical approach is warranted in patients without signs of any life-threatening conditions such as peritonitis and sepsis. In addition, subsequent imaging is needed for patients who are at high risk of their PI worsening into a life-threatening condition.

Ling et al. state that conservative methods include observation, hyperbaric oxygen therapy, antibiotics to inhibit intestinal bacterial infection, and endoscopy. Hyperbaric oxygen therapy alleviates symptoms by decreasing the partial pressure of gases in the venous system and facilitating gas diffusion out of the bowel wall. It also acts as a toxin against anaerobic bacteria in the intestinal tract. Hyperbaric oxygen therapy can also be supplemented with humidified oxygen via a Venturi mask or nasal cannula (4 to 6 L/min). Oxygen therapy should be used for two days after cyst disappearance in order to reduce the risk of recurrence. An antibiotic regimen used to treat PI is metronidazole 500 mg PO three times a day for up to three months. Further long-term management of PI is an elemental diet or a digestible formula diet composed of a liquid/powder form of daily nutrients. An elemental diet is completely absorbed in the intestines and reduces the production of gas by bacterial flora.

The indications for surgical intervention for PI are elevated white blood cell count, definitive imaging revealing portal venous gas, and clinical signs of sepsis or acidosis. Another more specific intervention is endoscopy with sclerotherapy for patients suffering from intestinal obstruction due to PI. Endoscopic treatment involves fine-needle aspiration of the many cysts in an attempt to exhaust the gas and relieve the intestinal obstruction. It can also be used to diagnose PI as it confirms the presence of gas-filled cysts via direct observation. Some patients may experience recurrence of intestinal obstruction due to PI. In this case, sclerotherapy of the wall after puncture may be performed to prevent the recollection or reexpansion of the cysts.[3][4][5][6][11]

Differential Diagnosis

Other pathologies that are part of the differential diagnosis must be ruled out. One of the more serious conditions is bowel ischemia. Infarction must be considered as a differential diagnosis, especially in patients with vascular disease, cardiac failure, and atrial fibrillation. The clinical presentation of diffuse abdominal pain with abnormal laboratory values warrants intestinal infarction rule out. Furthermore, with bowel ischemia, underlying causes such as strangulated internal hernia, abdominal abscess, and/or ileus must be considered.[1][12]

Prognosis

Predictors for poor prognosis in pneumatosis intestinalis include:

• pH < 7.3 
• Presence of portal venous gas
• Lactate level > 2 mmol/L
• Amylase level > 200 U/L
• Bicarbonate level < 20 ml/L

Surgical intervention is considered if patients, especially over 60 years of age, present with any obstructive symptoms, signs of sepsis and shock, or radiographic evidence of portal venous gas due to the high mortality associated. As per Greenstein et al. in 2007, the presence of emesis, leukocytosis (> 12 c/mm3), and age 60 and older are poor prognostic factors leading to surgical management. Furthermore, lactic acidosis, shock, and sepsis are also associated with unfavorable outcomes, including death.[4][6][13]

Complications

Pneumatosis intestinalis is associated with several complications, which are divided into intestinal and extraintestinal manifestations. Intestinal complications are mainly obstructions caused by gas cysts. This can lead to fecal impactions, which, if left untreated, can cause perforations due to colonic ulcers from long-standing increased intracolonic pressure. Perforation can lead to acute abdomen, septic shock, peritonitis, and other life-threatening conditions.

The presence of pneumatosis intestinalis with portal venous gas usually correlates with bowel ischemia in approximately 70% of cases. Extraintestinal complications are adhesions and compression of nearby structures. Cysts can cause outpouchings that directly compress adjacent organs. Rupture of these cysts can cause pneumoperitoneum, which requires urgent surgical intervention. Complications usually occur in approximately 3% of secondary pneumatosis intestinalis. Mortality from these complications can range from 50% to 75%, especially those with bowel ischemia.[3][4][7]

Consultations

Managing pneumatosis intestinalis requires an interprofessional team which includes:

• Hospitalists
• Intensivists 
• Radiologists
• Gastroenterologists
• Infectious disease specialists
• Colorectal/gastric surgeons
• Nurses
• Dietitians

Deterrence and Patient Education

Patient education and compliance with treatment are crucial to managing pneumatosis intestinalis. Nonadherence to treatment and lifestyle modifications can lead to consequences such as recurrence, septic shock, and death. Long-term lifestyle modifications include an elemental diet composed of digestible formula, which promotes near-complete absorption of its nutrients and reduces gas production in the intestines. Overall, patients should practice nutritional changes in order to prevent the recurrence of pneumatosis intestinalis.

Pearls and Other Issues

As stated earlier, pneumatosis intestinalis is not a primary condition in itself but a radiographic sign of underlying pathology. The COVID-19 respiratory illness is the cause of an ongoing global pandemic with an estimated 40 million confirmed cases. Although the coronavirus is known to affect many organ systems and is primarily a pulmonary pathology causing acute respiratory distress syndrome, gastrointestinal involvement has been reported. 

Most recently, Meini et al. reported a case of pneumatosis intestinalis in a patient with COVID-19 that resolved with conservative treatment of the respiratory illness. It is speculated that bowel wall damage and alteration of gut microbiota during COVID-19 infection of a patient can cause pneumatosis intestinalis. With the recent global outbreak, including over 1 million deaths, it is important to recognize the extrapulmonary manifestations of the disease, including pneumatosis intestinalis.[9]

Enhancing Healthcare Team Outcomes

The diagnosis and management of pneumatosis intestinalis require interprofessional team collaboration. Diagnosis begins with imaging interpreted by radiologists. Once a diagnosis is made, a treatment plan is devised by a team of providers, including hospitalists, intensivists, infectious disease specialists, gastroenterologists, and surgeons, depending on the clinical severity of the patient. Medical intensive care unit admission is also warranted if the patient becomes clinically unstable, requiring vasopressors and closer monitoring. A surgical consult is necessary for patients meeting the criteria of septic shock, presence of portal venous gas, acute abdomen, or perforation. However, patients who are septic at the time of diagnosis have increased mortality.[13] [Level 5] Nurses play a vital role in fluid resuscitation and antibiotic administration. A dietician must also be involved in diet modification post-treatment in patients.