Introduction

Non-occlusive mesenteric ischemia (NOMI) is a fairly rare but acute life-threatening complication (20-30% of all ischemic intestinal syndromes) with high mortality (up to 41-100%) [1, 2]. NOMI is a result of malperfusion of organs in mesenteric arterial system without mechanical obstruction of major arteries with thrombi or emboli. The causes of NOMI are diverse. The leading factors are cardiovascular diseases (heart failure, arrhythmia, systemic atherosclerosis, etc.), systemic hypovolemia (dehydration, bleeding), sepsis, vasopressor support, early postoperative enteral nutrition. NOMI pathogenesis consists in severe peripheral hypoperfusion with no blood flow in intramural arterial bed (peripheral vasospasm). Initial symptoms of non-occlusive ischemia are often unclear and non-specific that complicates timely diagnosis. Non-invasive diagnostic methods (ultrasound, CT) make it possible to assess the patency of aorta and its large branches, organ ischemia and necrosis. These methods are quite informative. Selective angiography is a more accurate but invasive method for imaging of small vessels. Nevertheless, some authors recognize selective angiography as the gold standard for diagnosis of NOMI [2]. In this manuscript, we summarized patients with NOMI after various resections and reconstructions of gastrointestinal tract.

The purpose of the study was to analyze the mechanisms of non-occlusive mesenteric ischemia (NOMI) after digestive tract surgery.

Material and methods

We analyzed all patients with NOMI operated on at the Department of Reconstructive Esophageal and Gastric Surgery of the Vishnevsky National Medical Research Center of Surgery. NOMI was diagnosed in 10 (0.4%) out of 2426 (100%) patients after reconstructive digestive tract surgery between 2015 and 2021. There were 4 women and 6 men aged 29 — 92 years (median 67 [60; 71.3]). Patients differed in both the underlying disease and surgical procedure. There were squamous cell carcinoma of the esophagus (n=2), adenocarcinoma of the gastroesophageal junction (n=2), benign disease of the esophagus including severe achalasia and extended stricture (n=2), primary multiple synchronous cancer (cancer of the gastroesophageal junction and the left kidney) (n=1), cancer of the sigmoid colon (n=1), gastric cancer (n=1), disease of the operated stomach (n=1). Esophagectomy was performed in 6 patients (gastric tube reconstruction — 5, colon interposition — 1) (Fig. 1).

Fig. 1. Surgery in a 29-year-old patient K.: transthoracic esophagectomy, proximal gastrectomy, total esophagoplasty with the left half of the colon.

A patient with primary multiple cancer underwent multi-visceral resection: subtotal proximal gastrectomy with small bowel interposition (Merendino-Dillard procedure) and resection of the left kidney (Fig. 2).

Fig. 2. Surgery in a 65-year-old patient S.: subtotal proximal gastrectomy (4/5), lymph node dissection D2, jejunum segment interposition (jejunogastroplasty by Merendino-Dillard).

One patient underwent left-sided hemicolectomy, one patient underwent distal subtotal gastrectomy with Billroth I reconstruction, and one patient after previous Balfour gastric resection underwent exclusion of the afferent loop and efferent loop transposition with reduodenization (Fig. 3).

Fig. 3. Surgery in a 75-year-old patient M.: efferent loop transposition with reduodenization.

All patients underwent standardized surgical interventions. No intraoperative complications were recorded.

Results

Median of surgery time was 372.5 (246.25; 548.75) min, blood loss — 450 (200; 725) ml. These parameters conformed to the type of surgery. We distinguished the following risk factors of early postoperative NOMI (1-2 postoperative days): vasopressor support for vasoplegia — 2, intrapleural bleeding — 1, acute reactive pancreatitis — 1, hypovolemia followed by acute cardiovascular failure — 1, early enteral nutrition — 1 patient. There were no specific clinical signs of non-occlusive ischemia. Lactic acidosis (> 4 mmol/l) in 1-3 days after surgery occurred in 7 patients. In 6 patients, fulminant NOMI after 1-2 postoperative day resulted multiple organ failure with subsequent septic shock. To identify the causes of septic shock, we performed contrast-enhanced CT. Gastrointestinal circulatory disorders including necrosis were found in 7 patients. Ischemia was observed in 3 patients. Other four patients had target organ necrosis (Fig. 4).

Fig. 4. Patient K., 29 years old. Coronal CT scan.

No contrast enhancement of colonic graft walls (arrows).

Selective SMA angiography was performed in none patient due to acute NOMI and non-specific clinical manifestations. NOMI was objectively confirmed in 2-5 days after surgery (median 3 [2; 4]). All patients underwent emergency redo surgery. Re-laparotomy was performed in 9 patients including 4 ones with several re-laparotomies, re-thoracotomy — in 1 patient. Multi-visceral gastrointestinal necrosis was observed in 5 patients (Fig. 5a, b), gastric transplant necrosis — 3, colon necrosis — 1, stomach stump necrosis — 1 patient (Table 1).

Fig. 5. Intraoperative images. Total necrosis of small and large bowel after 5 postoperative days.

Table 1. Damage to gastrointestinal organs

Note. EE — esophagectomy, POD — postoperative day.

In 1 patient, non-occlusive ischemia occurred not only in mesenteric artery bed, but also in celiac axis system (necrosis of liver and spleen). Resections were performed in 8 patients. Two patients underwent exploratory laparotomy. Eight patients died, 2 ones survived (Table 2).

Table 2. NOMI outcomes

Discussion

NOMI etiology is still not fully understood. Mesenteric arterial spasm is a prerequisite for NOMI. Spasm can persist even after correction of its causes. Ischemia-reperfusion syndrome complicates the course of NOMI. This syndrome results a massive release of toxic free radicals, nitrogen oxides and lipid peroxidation products into systemic circulation. The last ones serve as an additional damaging factor [3—5].

NOMI following early enteral nutrition in postoperative period is known. This is probably due to increased oxygen consumption by bowel walls following absorption of nutrients and secretory activity. In this case, oxygen consumption exceeds its delivery [3].

Risk factors of NOMI are advanced age, previous myocardial infarction, heart rhythm disturbances, heart failure, widespread atherosclerosis, major cardiac and thoracoabdominal surgery [4—6].

Thus, there are many risk factors of NOMI. However, only two triggering factors are known (severe vasoconstriction and hypovolemia). These factors result persistent tissue hypoperfusion and impaired intramural blood flow. In case of NOMI following early postoperative enteral nutrition with hyperosmolar solutions, microvascular sludge is an analogue of peripheral vasoconstriction. Over time, ischemia becomes irreversible, and multiple tissue necrosis occurs. For example, 8-hour small bowel ischemia is irreversible even after restoration of intramural blood flow. In addition, episodes of hypoperfusion can be repeated many times.

Non-occlusive ischemia after esophagectomy with esophagoplasty is rare. Statistical data on this disease in esophageal and gastric surgery are absent. Only case reports are available. About 12 cases of NOMI after esophagectomy are described in the literature [7].

In 2 patients, NOMI was accompanied by graft necrosis. Miura K. et al. [7] described similar cases. Transplant necrosis is a rare but severe complication of esophagoplasty [8, 9]. Risk factors of this complication are heart failure, postoperative hypotension, vasopressor support, etc. [9]. It should be noted that risk factors are identical to those in NOMI [2, 10]. Thus, graft necrosis may be a local manifestation of NOMI. Perhaps, multi-visceral lesion did not have time to be realized in 3 patients with necrosis of only the gastric graft due to timely diagnosis, intensive care and emergency surgical intervention.

Early diagnosis of NOMI determines its prognosis. Unfortunately, NOMI resulted septic shock and fulminant multi-visceral necrosis after 1-2 postoperative days in 60% of patients. Hypothesis of NOMI pathogenesis in our patients is schematically shown in Fig. 6.

Fig. 6. Hypothesis of NOMI mechanism.

NOMI is difficult to diagnose. In most cases, it cannot be recognized in time. Clinical diagnosis is difficult due to non-specific symptoms. In this study, none patient presented complaints to suspect at least an “acute abdomen”. All patients underwent standardized surgical interventions without intraoperative complications. Symptoms of NOMI occurred at the stage of necrosis.

Signs of acute abdominal ischemia and extensive necrosis (including multi-visceral necrosis) in early postoperative period in most patients suggest intraoperative exposure to NOMI triggering factors.

In addition, one cannot consider laboratory data only. There are no markers specific for acute non-occlusive ischemia. Their pooled assessment is necessary. In most patients, demonstrative changes (lactate acidosis, metabolic acidosis, high CRP, leukocytosis) were detected after 3 postoperative days and later. This period also corresponded in time to the phase of necrosis. For this reason, MSCT could not be performed at the stage of reversible ischemia of the target organ.

Typical radiological signs of acute non-occlusive ischemia are wall thickening, decrease / absence of contrast enhancement by of hollow organ walls, enlargement of its lumen and, in more severe cases, pneumatosis of the walls (the so-called intestinal pneumatosis) with a gas spread through the portal vein system (Fig. 7).

Fig. 7. NOMI after 2 postoperative days.

Axial CT scan. Absence/reduction of contrast enhancement of small bowel walls (black arrows), pneumatosis of the walls (white arrows).

In some cases, contrast enhancement of the bowel wall can be normal, and even increased due to reperfusion. No contrast enhancement of intestinal walls is a specific, but insensitive symptom of acute mesenteric ischemia [11]. Schieda et al. [12] reported intestinal pneumatosis with a gas spread through the portal vein system as a specific and significant prognostic sign of NOMI in 100% of cases. However, these findings are common in various other diseases including ischemic colitis [13]. Thus, impossibility of timely diagnosis of NOMI syndrome at the stage of reversible ischemia explains high mortality in these patients.

Considering heterogeneity of patients regarding the underlying and comorbid diseases, age and surgical procedure, we can assumed the multifactorial nature of NOMI that entails complexity of experimental modeling.

Conclusion

Diagnosis of NOMI is difficult because the early symptoms of the disease are variable and non-specific. Manifestation of NOMI in the form of septic shock in 60% of patients was associated with fulminant multi-visceral necrosis after 1-2 postoperative days. Perhaps, symptoms of acute abdominal ischemia were masked by intraoperative sedation. Therefore, timely diagnosis of NOMI at the stage of acute ischemia was impossible in our sample. Extensive visceral necrosis in early postoperative period is probably associated with intraoperative critical ischemia of digestive organs. This fatal complication deserves further study including experimental model with intraoperative analysis of visceral perfusion.

The authors declare no conflicts of interest.