Outcome of acute mesenteric ischaemia in patients with Covid-19 infection

INTRODUCTION

Since the first reported case of Covid-19 in China, the pandemic spread quickly over the globe causing substantial morbidity and mortality.¹ Although respiratory complications received most attention in the management of SARS-CoV-2 infections, certain Covid-19 patients may also have gastrointestinal symptoms.² Covid-19 has also been implicated in coagulopathy, generally in patients with serious ailments. Laboratory results of elevated D-dimer/fibrinogen levels and prothrombin time found in patients with severe illness and postmortem findings of venous thromboembolism in Covid-19 supports the causal relationship between Covid-19 and coagulopathy.³ Although the reported incidence of arterial thrombosis is lower compared to venous thrombosis in patients with Covid-19, it can still present as ischaemic stroke, acute limb ischaemia, renal infarcts and rarely, acute mesenteric ischaemia (AMI).⁴

Despite being extremely rare, AMI is a potentially life-threatening complication of Covid-19 infection. AMI can progress to intestinal necrosis and, if left untreated, can result in mortality due to peritonitis and septic shock. Thus, early identification and management of such a rare manifestation can prevent mortality. We analyzed the characteristics and clinical outcomes of AMI in Covid-19 patients. We also explored the necessity of prophylactic anticoagulant use in Covid-19 patients to prevent these unusual but deadly thrombotic complications.

THE CASE SERIES

Our retrospective, observational study was done at a single tertiary care centre in India from May 2021 to April 2022. All patients, 18 years old or older, admitted with confirmed Covid-19 infection (defined as a positive result on a reverse transcriptase– polymerase chain reaction on a nasopharyngeal sample) were included. Patients with a diagnosis of AMI based on clinical and radiological criteria were included.

The primary outcome of the study was the need for surgical intervention. The decision for surgery was made based on the patient’s clinical status by a multidisciplinary team. The secondary outcome of the study was in-hospital mortality associated with AMI. Clinical, laboratory, radiological, and surgical data of patients with Covid-19 and AMI were retrieved and analyzed.

Ten patients had confirmed Covid-19 infection and AMI, 8 (80%) were males with a median age of 57 (range 40–70) years. The most common presenting symptoms were pain abdomen (100%) and vomiting (60%). The median interval from diagnosis of Covid-19 infection to the onset of gastrointestinal (GI) symptoms was 11 days (range: 4–45 days). Eight (80%) patients had associated comorbid conditions such as hypertension, diabetes and prior stroke. Two of our patients were on antithrombotics (one on aspirin and one on apixaban) during their infection with Covid-19 but still developed mesenteric ischaemia. However, their symptoms were minor and subsided with conservative treatment.

When analyzing the site of thrombosis, the superior mesenteric artery (SMA) was the most common vessel to be involved (8/10, 80%), with one patient having inferior mesenteric artery involvement and another having involvement of all 3 splanchnic arteries. The mean leucocyte count, neutrophil count and platelet levels were within the normal range, while C-reactive protein was raised in all patients (Table 1). The mean values of the international normalized ratio and activated partial thromboplastin time were above the normal thresholds. D-dimer values were almost at the maximum limit, although fibrinogen levels for each patient were above the normal range.

Of the 10 patients, 1 had only jejunal involvement, 5 had only ileal involvement and 4 had jejunoileal involvement. Only 1 patient had a perforation. Seven patients underwent surgery, while 3 patients were managed medically. All patients were started on low molecular weight heparin or unfractionated heparin based on renal function. Two of the 3 patients managed conservatively were too unstable to undergo surgery. Histopathological examination of all the resected specimens showed transmural necrosis with fibrinopurulent inflammation, marked haemorrhage and congestion. Four patients died (the reasons being renal failure and sepsis leading to respiratory failure), and all of these patients also had comorbid conditions. All other patients were treated and discharged from our hospital on either apixaban or dabigatran for at least 6 months. Table 2 summarizes the clinical parameters, management and outcome of all the included patients.

DISCUSSION

A high index of suspicion should be maintained by healthcare providers regarding this life-threatening complication of Covid-19 to enable timely intervention. Treatment varies from a conservative approach in mild cases presenting early to major surgeries and radical resections in severely affected patients. It is essential to understand the varied systemic manifestations and complications of SARS-CoV2 for optimal patient care.

Singh and Kaur reviewed the literature on Covid-19 and AMI and identified 13 patients. Six patients had prior comorbid conditions. Four patients had concurrent thrombosis at other sites, including the portal vein, superior mesenteric vein, splenic vein and renal artery. Of the 13 patients, 10 had surgery and 4 died.⁵ The clinical profile and outcome of patients in this analysis were similar to our study. In another study, Aktokmakyan et al. described the incidence, characteristics and clinical outcomes of patients presenting with AMI during Covid-19.⁶ Amongst the 63 cases undergoing emergency surgery, mesenteric ischaemia was the aetiology in 5 of the 6 Covid-19-positive patients. The presence of hypercoagulation status in these patients was evidenced by high D-dimer and fibrinogen levels. There were no complications, and only 1 patient (20%) died.

AMI in Covid-19 is associated with a high mortality of 60%–80% which can be reduced with timely intervention. Balani et al. reported a case of AMI in Covid-19 involving the SMA, which was managed successfully with catheter-directed thrombolysis followed by thrombus aspiration. The authors emphasized that an early diagnosis and radiological management of AMI can prevent a major bowel surgery in patients with Covid-19, thereby negating the risk of morbidity or mortality associated with that surgery. An endovascular approach can help improve outcomes by reducing the risk of mortality and morbidity associated with open surgery.⁷

Subsequently, Kerawala et al. conducted another systematic review, identifying 22 case reports and six case series, including 41 patients. One-third of the patients had associated comorbid conditions, amongst which hypertension was the most common. An exploratory laparotomy and gangrenous bowel segment resection were performed on 33 (80.5%) patients. Mortality was reported amongst 14/41 (34%) cases, although the follow-up duration was short in a few studies and might not be the actual mortality rate. Amongst the patients who died, 12 (86%) had surgical resection of the necrotic bowel and still succumbed to the disease.⁸ The mortality rate in our study was 40%, similar to this analysis. These findings highlight that AMI is associated with major mortality in Covid-19 and thus warrants early identification and management, as early diagnosis can be associated with a reduction in mortality of up to 50%.⁹

Covid-19 infection can contribute to AMI and associated complications through multiple pathways: (i) angiotensin-converting enzyme 2 mediated invasion of enterocyte followed by endothelial inflammation; (ii) increased procoagulant factors such as factor VIII, von Willebrand factor; and (iii) activated coagulation and fibrinolytic pathways triggered by cytokine storm. Additional explanations for the hypercoagulable states may be the presence of high numbers of prothrombotic circulating microvesicles, prolonged bed rest in critically ill patients and the presence of hypoxia in patients with Covid-19.¹⁰

Patients already on prophylactic anticoagulation can also develop AMI, as evident in the our study and previous reports.^11–14 Having a high index of suspicion and obtaining contrast computed tomography imaging early are essential for a prompt diagnosis. Any patient with Covid-19 infection presenting with acute onset severe pain abdomen should undergo a CT scan. AMI should be suspected in the presence of an oedematous, thick wall and dilated bowel (>3 cm). The presence of pneumatosis intestinalis or portal venous gas may indicate intestinal ischaemia. However, in severe Covid-19 patients, pneumatosis may be secondary to mechanical ventilation, which must be taken into account. A thick, non-enhancing bowel suggests bowel infarction, while bowel wall discontinuity with focal air-containing collection indicates perforation.¹⁵

To conclude, mesenteric ischaemia is common in Covid-19 patients. AMI should be a differential diagnosis in all patients with Covid-19 presenting as acute abdomen. The bowel can be salvaged with early identification and medical or endovascular intervention, while delayed diagnosis usually results in bowel gangrene requiring surgical resection. Patients on prior anticoagulation can still develop AMI, but the severity is usually low. Mortality remains high even with surgical resection. Further multicentric studies with a larger number of patients are warranted to decide on the optimal management strategy.