Prognostic factors of acute mesenteric ischemia in ICU patients

Acute mesenteric ischemia (AMI) is often an underdiagnosed cause of acute abdomen and is still followed by a high mortality and morbidity rate, despite intensive care therapy [1‐4]. AMI may be subdivided into four different types according to the pathophysiology. Embolic and thrombotic occlusion is responsible for approximately 2/3 of cases, while nonocclusive mesenteric ischemia (NOMI) and mesenteric venous thrombosis (MVT) represent each 1/6 of cases [5]. Early diagnosis is often impaired due to the lack of sensitivity and specificity of the clinical features and biomarkers. Computed tomography with angiography (CTA) is currently the “gold standard” diagnostic procedure in AMI, with an estimated sensitivity and specificity of 91 and 99%, respectively [6, 7]. However, CTA findings in the early stages of the affection may be more subtle, and the sensitivity is probably overestimated [1]. AMI may occur as a primary diagnosis but is also observed as a complication in ICU patients admitted with other comorbidities. To our best knowledge, few studies have looked specifically at the outcome of AMI in ICU patients [8].

The primary aim of our study was to assess the prognostic factors of arterial AMI in ICU patients admitted in a tertiary care center over a period of 17 years. Additional endpoint was to determine if AMI was the primary cause of admission in the ICU or if it was secondary to an underlying condition. Finally, we developed a score predicting AMI mortality in ICU patients.

The detailed results are presented in Tables 1 and 2.

In the present study, the 30-day mortality rate for the 214 included patients was 71%, while in-hospital mortality was 68%. These mortality rates are congruent with those reported by the systematic review from Schoots et al. [7] and the meta-analysis from Adaba et al. [15], where in-hospital mortality rates were 71.6 and 63%, respectively.

Our mortality rate is also supported by a multicenter study by Leone et al. [8]. This study assessed risk factors of ICU mortality in AMI in France, and reported similar mortality rates, with 58% of ICU mortality and 63% of in-hospital mortality. With a 780-patient cohort, this study is currently the largest that assessed prognostic factors of AMI in ICU. However, it did not discriminate venous from arterial AMI. Our monocentric study extended on a longer period of time (17 years) than the study by Leone et al. (6 years). It assesses the mortality in an ICU belonging to a tertiary care center, with a proportion of patients referred from other ICUs in a critical condition.

Finally, the high mortality rate in our series is consistent with the particularly high incidence of NOMI. This form mainly occurs in patients presenting a severe and acute critical illness. The clinical presentation is often insidious and nonspecific, leading to delayed diagnosis [16, 17]. This explains also in our series the weak association of AMI with former or new onset atrial fibrillation.

Unlike in other studies [8, 18‐20], age did not seem to be an independent risk factor of mortality in AMI.

We also underline the weak role of prior medical history or previously developed comorbidities on mortality. Only prior history of arterial hypertension seemed to improve the outcome. The reason for this speculative protective effect of arterial hypertension remains unclear, but could be related to a better preservation of pressure flow autoregulation in the splanchnic area [16].

The poor prognosis of AMI was also related to the number of organ dysfunctions as illustrated by the results of the univariate and multivariate analysis. It mainly refers to patients admitted with sepsis and who developed shock, acute kidney injury, and who required vasopressors and/or inotropes and mechanical ventilation. Regarding the use of vasoactive drugs, we cannot exclude its role in the increase of splanchnic vasoconstriction, even if vasopressin was not administered to our patients.

The prognostic value of arterial lactate concentration was also confirmed, and particularly the rise in arterial value within the first 24 h following diagnosis. Elevated serum lactate levels > 2 mmol/l was associated in irreversible intestinal ischemia in established diagnosis of AMI [21] While single lactate level is thought to be a strong predictor of subsequent organ dysfunction and mortality, it appears that lactate clearance is strongly associated with all-cause mortality in critically ill patients [22]. In the context of AMI, persistently elevated serum lactate is reflecting ongoing splanchnic hypoperfusion or progression of multiple organ failure. The diagnostic performance of lactate clearance may be even higher than in patients with sepsis. It has to be kept in mind that a normal value for arterial lactate does not exclude the diagnosis of AMI and that an isolated high lactate concentration may also reflect a late diagnosis.

On the other hand, anticoagulation initiated following diagnosis was associated with a better outcome in arterial AMI. While a continuous infusion of unfractionated heparin is a key treatment for venous mesenteric thrombosis, no benefit was clearly demonstrated to date in arterial AMI [23].

Derived from the multivariate analysis, we are proposing a predictive score of mortality that includes the maximal dose of vasopressors, the use of anticoagulation and the arterial delta lactate.

Regarding surgical approach, only a very few number of patients could benefit from revascularization. Intestinal resection was required for most of the cases and surgery, even if performed early, did not seem to improve prognosis. According to recent guidelines, more patients had second-look laparotomy over the last years of this survey. Damage control surgery (DCS) is now an important adjunct for critically-ill patients as it may allow to monitor the restoration of splanchnic perfusion [24].

Even if an autopsy was not performed in all deceased patients, the final cause of death appears to be in most of cases a multiple organ failure, often already present at the time of diagnosis. Eventually, in a significant number of medical files, a surgical abstention was probably decided due to the extent of the disease or to the patient’s condition following the development of multiple organ failure.

The limitations of this retrospective analysis have to be acknowledged.

First, this study does not permit to analyze the diagnostic accuracy of CTA, because according to our inclusion criteria, only patients with confirmed (and not only suspected) AMI were enrolled. The radiologist protocol did not include a reading grid, resuming every item contributing to AMI diagnosis. We deemed the CTA feature as absent if it was not explicitly mentioned in the radiologist protocol. In this study, the diagnostic and prognostic weight of bowel wall hypo-enhancement seems to be high. In ICU, the presence of an isolated pneumatosis intestinalis is not uncommon and can be related to other etiologies. We do not have data about false positive cases (e.g., pneumatosis intestinalis and AMI excluded by laparotomy). Finally, while significant progress has been made in CTA diagnosis over the last years, it appears unlikely that patients with NOMI could benefit from endovascular revascularization [25].

Second, the prevalence of some of the PMH or comorbidities may have been underestimated, because they have been reported from patients’ files. We estimate that most of PMH and comorbidities were reliably and consistently consigned in the medical files, making this bias minimal, except for hypercholesterolemia, chronic inflammatory disease and hypercoagulability. Concerning hypercholesterolemia, often not reported in the files, we attempted to limit the bias by searching for cholesterol-lowering agents in the medication history or for previous laboratory results showing hypercholesterolemia. The reason behind the underestimation of hypercoagulability and chronic inflammatory disease is that these conditions are often unknown in the setting of the ICU.

Third, the value arterial lactate 24 h after diagnosis is probably underestimated. Indeed, rapidly deceased patients (in less than 24 h) would probably have, considering our results, increased or persistently high concentrations of arterial lactate. The consideration of this bias strengthens the prognostic value of arterial lactate 24 h after diagnosis and arterial delta lactate, two variables identified as associated with poor outcome. Patients with AMI as main ICU admission diagnosis often do not have data about total platelet count 24 h prior to diagnosis. It could have led to an underestimation of the platelet count, because these patients probably had a mean platelet count higher than patients who were admitted in ICU for another reason, the latter in whom platelets could have decreased from other conditions.

Finally, as the period of data analysis extended over 17 years, even if the medical staff remained unchanged, significant changes may have occurred in diagnostic and therapeutic procedures over time.

Fatalities after AMI were related to a high incidence of multi-organ failure. The monitoring of arterial lactate appeared helpful to identify the patients with a poor prognosis.