Conservative versus Surgical Treatment of Pneumatosis Intestinalis: Experience from a Multidisciplinary Center

Background

Pneumatosis intestinalis (PI) is the term for gas found in the intestinal wall using imaging methods, mostly by abdominal computed tomography (CT), with the detection rate of 0.37% [1]. PI can be an incidental finding on imaging that does not require treatment, or it can be an urgent condition requiring emergency intervention.

PI is divided into 2 groups: primary PI (15%), which is usually asymptomatic and does not require intervention, and secondary PI (85%), which mostly requires intervention [2]. PI can be benign or life-threatening. Benign PI can be caused by a variety of factors such as pulmonary disease, systemic disease (eg, scleroderma, lupus, AIDS), intestinal inflammation, medications (eg, steroids, chemotherapeutic drugs), or iatrogenic. Non-benign PI can be caused by intestinal ischemia, obstruction, enteritis/colitis, appendicitis, toxic caustic ingestion, toxic megacolon, or collagen vascular disease [3–5].

There are 2 main hypotheses to explain PI – mechanical and bacterial factors [6]. Typically, mechanical factors comprise increased pressure in the intestinal lumen and damage to the intestinal mucosa due to inflammation and ischemia. Due to these factors, gas in the lumen enters the intestine’s submucosa and serosa layers, penetrating the mesenteric vessels, which eventually lead to the hepatic portal vein. Rarely observed, another mechanical cause is gas rupture from the alveoli of patients with chronic obstructive pulmonary disease. This gas dissects along the blood vessels in the mediastinum and spreads to the mesentery, forming gas bubbles under the intestinal serosa. Bacterial factors include the infiltration of gas-producing bacteria through the intestinal wall and alteration of the gas composition and concentration gradient in the intestinal lumen.

Currently, there are no specific clinical guidelines for treating and diagnosing PI. Although some studies used clinical algorithms to identify patients indicated for surgical intervention and prevent non-therapeutic laparotomies [7,8], most of these data come from case reports, or retrospective studies with small sample size. Therefore, the most crucial component of the PI treatment plan is thorough and rigorous clinical assessment, which serves as the basis for choosing between conservative and surgical treatment.

Case Reports

CASE 1:

An 80-year-old man with a past medical history of chronic obstructive pulmonary disease, drug-induced adrenal insufficiency, and aneurysm dissection of the celiac and superior mesenteric arteries presented with a 1-month history of dull abdominal pain around the navel. He was afebrile, hemodynamically stable, and was passing yellow, moldy stools without blood or mucus. Physical findings were unremarkable, with pressing pain around the navel and no significant rebound or guarding. Admission laboratory tests revealed a complete blood count within normal range, as well as normal coagulation tests, normal pro-calcitonin, lactate, creatinine, and pH level (white blood cell count: 9.6×10⁹ cells/mm3; red blood cell count: 4.82×10¹² cells/mm³; hemoglobin: 149 g/l; platelet count: 192×10⁹ cells/ mm³; prothrombin time: 12.7 s; activated partial thromboplastin: 24.7 s; INR: 0.92; pro-calcitonin: 0.05 ng/mL; lactate 1.13 mmol/l; eGFR 68.8 mL/min/1.73 m²; pH 7.468).

Abdominal ultrasound showed distended and bloated small intestines with little free fluid between the loops. Abdominal CT scan with intravenous contrast revealed gas bubbles within the terminal ileum wall and mesenteric vessels (Figure 1). However, the entire the ileum wall was well perfused. No thrombosis was detected inside the mesenteric vessels or the hepatic portal vein.

The patient was treated conservatively with parenteral nutrition and intravenous antibiotics for 5 days. He was released from the hospital when tolerance for solid food had improved and the abdominal pain had gradually subsided. A follow-up abdominal CT scan after 3 months disclosed a decrease in size of gas bubbles in the intestinal wall. Additionally, there was no sign of gas bubbles left in the mesenteric vessels.

CASE 2:

An 86-year-old man who had a history of hypertension was transferred to the emergency department after experiencing abdominal pain around his navel for 3 days. The patient was nausea, bloating, afebrile, and had frequent loose yellow stools. An unstable hemodynamic was noted in the previous hospital, with a pulse rate of 73 beats per minute and a low blood pressure of 80/50 mmHg, rising to 100/70 mmHg after Noradrenalin infusion of 0.12 mcg/kg/min. Additionally, intravenous antibiotics (Ceftazidime 1 g and Ciprofloxacin 400 mg) were also administered. The patient was transferred to our facility after 6 hours. Clinical examination showed stabilizing vital signs, no fever, moderate abdominal distention, and tenderness around the umbilical area. An anorectal examination showed yellow stool without blood or mucus. Blood tests results showed that the white blood cell count had increased from 9.32 to 14.4×109 cells/mm3; serum lactate level rising from 4.88 to 6.48 mmol/l; the prothrombin time was slightly elevated at 19.2 s (INR: 1,43); blood pH level had decreased from 7.327 to 7.278; and the albumin level was significantly lowered to 17.6 g/l. The hemoglobin level, platelet count, pro-calcitonin level, activated partial thromboplastin time, and estimated glomerular filtration rate were within normal range. An abdominal CT scan with intravenous contrast showed pneumatosis intestinalis in the terminal ileum, with reduced contrast enhancement of the ileum wall. There was also gas in the portal vein and the inferior mesenteric vein, without any sign of thrombosis (Figure 2A). A diagnostic laparoscopy identified ischemic necrosis on 200 cm of the small intestine, without any evidence of a perforation, as well as cloudy fluid and pseudomembranes dispersed throughout the abdominal cavity (Figure 2B). The necrotic section was resected and an ileostomy was created. Postoperative pathology showed hemorrhagic and necrotizing enteritis. After surgery, the patient received resuscitation treatment, including mechanical ventilation mode VA/C (RR 25 times/minute, PEEP 5 cmH2O, FiO2 30–50%), and was weaned from the ventilator on postoperative day 5. He received parenteral nutrition and intravenous antibiotics, including Meropenem, Ciprofloxacin, and Metronidazole. Noradrenalin was also administered at a starting dose of 0.25 mg/kg/minute and gradually decrease over 4 days. On postoperative day 9, the patient’s condition improved, he was transferred to the Gastrointestinal Surgery Department for additional care, and was discharged from the hospital on postoperative day 16.

CASE 3:

A 62-year-old man was admitted to the Gastrointestinal Surgery Department with indication for stoma closure. He had a background of ileocecal resection with double-barrel stoma due to a perforation of the terminal ileum (postoperative pathology showed acute inflammation with necrosis of the ileum), type B chronic obstructive pulmonary disease (currently treated with Berodual 0.02mg/0.05 mg 2 strokes per day and Spirava Respima 0.0025 mg 2 strokes per day), drug-induced adrenal insufficiency (currently treated with Prednisolone 5 mg twice a day), essential hypertension, chronic ischemic heart disease, dissection and thrombosis of the superior mesenteric artery (currently treated with Plavix 75 mg, Bisoprolol 2.5 mg, and Atorvastatin 40 mg), diabetes mellitus type 2 (currently treated with Trajenta Duo 2.5/500 mg).

Colonoscopy before the first surgery showed an ulcer 1.5cm in diameter with pseudomembrane in the terminal ileum (5 cm from the ileocecal valve), and a 7-mm polyp (10 cm from the ileocecal valve). Diagnostic test results for specific inflammatory diseases were unremarkable, composed of a negative Interferon Gamma Release Assay; a normal stool calprotectin level of 7.23 ug/g; a negative stool microscopy, and a negative gastrointestinal pathogens panel (Panel 2).

Stoma reversal was performed using a hand-sewn end-to-end anastomosis. After surgery, the patient was treated with parenteral nutrition. In postoperative day 3, he reported worsening abdominal distension and was vomiting a large volume of yellow fluid. Clinical examination showed clamped blood pressure of 80/50 mmHg, rapid pulse of 110 pulse per minute, moderate abdominal distention, and tenderness around the navel without guarding. Nasogastric tube output was 3000 ml of clear yellow fluid, but then 500 ml of bright red blood was aspirated from the stomach. Abdominal ultrasound showed many scattered “comet-tail” artefacts suggesting gas in the portal vein, the small intestine loops in the right abdomen were filled with fluid, suggesting gas in the intestinal wall and necrosis (Figure 3A). An abdominal CT scan showed many gas bubbles in the wall of the stomach, duodenum, and high loops of small intestine and in the portal vein and superior mesenteric vein. The stomach, duodenum, and small intestine wall were poorly enhanced (Figure 3A). There were no signs of thrombosis in the mesenteric vessels or free abdominal fluid.

He was given blood transfusion, hemostatic medications (tranexamic acid), intravenous antibiotic (meropenem), and continuous vasopressor injection (Noradrenalin 1 mcg/kg/minute). Emergency endoscopy discovered a large amount of blood and blood clots in the stomach, there was a 1.5-cm Forrest IIb ulcer in the gastric bulge, and erosive gastritis was also noted spreading down to the body of the stomach. The mucosa of the duodenum was noticeably ischemic, withered leaf-colored, and contained gas bubbles (Figure 3B).

Blood tests results showed that the red blood cell count had decreased from 5.52 to 4.42×10¹² cells/mm³; hemoglobin level fell from 143 to 113 g/l even after blood transfusion; the prothrombin time and activated partial thromboplastin time were also longer at 23.8 s and 49.2 s, respectively. The white blood cell count and platelet count, levels of pro-calcitonin, albumin, lactate, and blood pH, and estimated glomerular filtration rate were within normal range.

The patient was transferred to the ICU for resuscitation management, which included intravenous antibiotics, vasopressors, and mechanical ventilation. After 3 days, an abdominal CT scan revealed no signs of ischemia or gas in the intestinal wall (Figure 3C). After 2 weeks of treatment, the patient was still on mechanical ventilation, antibiotics, and high doses of vasopressors, had severe -gastrointestinal bleeding due to a D3 duodenal ulcer, and underwent gastroduodenoscopy embolization. After 7 weeks of treatment, he developed a fourth-degree sacrococcygeal ulcer, which required excision and continuous suction through vacuum-assisted closure (VAC). After experiencing septic shock caused by wound infection with multiresistant Proteus mirabilis, Klebsiella, Pseudomonas aeruginosa pneumonia, and urinary tract infection caused by Acinetobacter baumanii, the patient was terminally discharged from the hospital as requested by his family, with death prognosis.

Discussion

PI is primarily diagnosed by abdominal CT scan. It is a sign of an underlying condition that may require urgent intervention [2]. The 2 main hypotheses to explain PI are mechanical and bacterial factors. In cases 1 and 3, the patients both had high-risk factors of cardiovascular disease, atherosclerosis, chronic obstructive pulmonary disease, and long-term corticosteroid use. These are the causes that aggravate non-obstructive intestinal ischemia (NOMI). When there are precipitating factors such as lack of fluid, paralytic ileus, or fluid stagnation, the pressure in the intestinal lumen increases, leading to NOMI and PI. Case 2 suggests that gastrointestinal infection may be a factor promoting NOMI in patients with underlying atherosclerotic vascular disease.

HPVG, with or without the presence of PI, is a serious sign [9,10]. Intra-abdominal infection, intestinal ischemia, intraluminal distention, and structural alterations in the intestinal wall are the most common causes. HPVG alone can occur in patients with intestinal obstruction, intestinal ischemia, inflammatory bowel disease (IBD), gastric ulcers, diverticulitis, abdominal trauma, or following interventional endoscopic procedures. When PI and HPVG coexist, it frequently indicates intestinal ischemia and necrosis. The prognosis is poor, and most cases require urgent surgery, with the mortality rate of 75–90% [6]. Furthermore, PI with HPVG can also cause anastomotic leak, perforated viscus, and secondary abdominal infection with gas-producing bacteria [11].

Currently, there are no specific guidelines for managing PI. Most published data were derived from case reports or small sample size retrospective studies. According to these studies, exploratory surgery is needed when PI combines with 1 of 4 signs: peritonitis, metabolic acidosis (pH <7.3), serum lactate level >2 mmol/l, or the presence of HPVG [2]. Our report also has a small sample size, thus statistical analysis could not be performed, but we drew the same conclusion as previous studies. Therefore, surgical intervention is determined not only by the PI/HPVG sign but also depends on the patient’s condition, clinical examination, and blood tests.

Both ultrasound and CT scan can detect PI and HPVG. However, CT has higher sensitivity and specificity. In case 3, abdominal ultrasound detected gas bubbles in the intestinal wall/portal vein and assessed the amount of abdominal fluid, but could not evaluate the intestinal mucosal perfusion. CT scan is currently considered the criterion standard in diagnosis of PI and HPVG. It can help medical professionals determine the condition of the intestinal wall as well as the extent of damage (eg, dilating and thickening wall, decreased mucosal perfusion), the abdominal cavity condition (eg, mesenteric edema, ascites, free abdominal air), and the mesenteric vascular status (atherosclerosis, obstruction of mesenteric arteries or veins), thus aiding in orientation of management [12,13].

In addition, it is crucial to distinguish between HPVG and biliary air. HPVG is concentrated in the periphery of the liver parenchyma (<2 cm from the capsule), while biliary air is concentrated mainly in the center. This characteristic is due to the difference in flow direction; the blood in the portal vein flows from the center to the periphery and the bile flow from the periphery to the center, so the gas in the portal vein concentrates mainly in the left lobe of the liver [14]. In this report, in case 2, the gas was concentrated in the left lobe with intestinal necrosis in the terminal ileum, whereas in case 3 the gas was concentrated in both lobes. This can be explained because in case 3 the location of anemia was concentrated in the stomach, duodenum, and the first part of the small intestine, where there was a rich venous network draining to the portal vein. Thus, it can be assumed that gas distribution in the portal vein can suggest the extent and location of intestinal ischemia, but more studies with better reliability are needed to prove this.

PI and HPVG are highly predictive of mortality in patients with bowel injury requiring emergency surgery [2]. However, for patients whose condition cannot tolerate surgery, conservative treatment should be considered in discussion with the patient and relatives. Gonda et al [6] reported a 25% rate of successful conservative treatment in the PI with HPVG group. Also in that study, factors that predict mortality after multivariate analysis included the presence of abdominal fluid, shock, and peritonitis. The mortality rate is up to 90% when 2–3 signs appear simultaneously. Blood test results (eg, white blood cell count, C-reactive protein level, and lactate concentration) were higher in the patients who died than in the recovery group, but the difference was not significant. In our study, case 2 had all 3 signs mentioned above and the patient died soon thereafter. Case 3 only had 1 of the 3 signs (presence of shock). Although he had many risk factors such poor general condition, inability to tolerate surgery, and suspected nondissectable ischemia (duodenum and the first loop of jejunum), the signs of PI and HPVG disappeared after 3 days of resuscitation treatment in the ICU. This patient responded well to resuscitation treatment because the intestinal ischemia was mainly due to NOMI combined with paralytic ileus, which damaged the mucosa, facilitating bacteria translocation into the intestinal wall and portal vein. However, due to multi-organ infection, prolonged shock, and high-dose vasopressors, he did not recover.

Conclusions

PI with HPVG suggests a poor prognosis that requires emergency surgery, with the main cause being intestinal ischemia and necrosis. The decision to manage conservatively or surgically depends on the patient’s condition and other criteria such as peritonitis, free fluid in the abdominal cavity, and shock. Physicians should also weigh the benefits and risks of surgical intervention in critically ill patients.