Incidence, diagnosis, management and outcome of acute mesenteric ischaemia: a prospective, multicentre observational study (AMESI Study).

BACKGROUND: The aim of this multicentre prospective observational study was to identify the incidence, patient characteristics, diagnostic pathway, management and outcome of acute mesenteric ischaemia (AMI). METHODS: All adult patients with clinical suspicion of AMI admitted or transferred to 32 participating hospitals from 06.06.2022 to 05.04.2023 were included. Participants who were subsequently shown not to have AMI or had localized intestinal gangrene due to strangulating bowel obstruction had only baseline and outcome data collected. RESULTS: AMI occurred in 0.038% of adult admissions in participating acute care hospitals worldwide. From a total of 705 included patients, 418 patients had confirmed AMI. In 69% AMI was the primary reason for admission, while in 31% AMI occurred after having been admitted with another diagnosis. Median time from onset of symptoms to hospital admission in patients admitted due to AMI was 24 h (interquartile range 9-48h) and time from admission to diagnosis was 6h (1-12 h). Occlusive arterial AMI was diagnosed in 231 (55.3%), venous in 73 (17.5%), non-occlusive (NOMI) in 55 (13.2%), other type in 11 (2.6%) and the subtype could not be classified in 48 (11.5%) patients. Surgery was the initial management in 242 (58%) patients, of which 59 (24.4%) underwent revascularization. Endovascular revascularization alone was carried out in 54 (13%), conservative treatment in 76 (18%) and palliative care in 46 (11%) patients. From patients with occlusive arterial AMI, revascularization was undertaken in 104 (45%), with 40 (38%) of them in one site admitting selected patients. Overall in-hospital and 90-day mortality of AMI was 49% and 53.3%, respectively, and among subtypes was lowest for venous AMI (13.7% and 16.4%) and highest for NOMI (72.7% and 74.5%). There was a high variability between participating sites for most variables studied. CONCLUSIONS: The overall incidence of AMI and AMI subtypes varies worldwide, and case ascertainment is challenging. Pre-hospital delay in presentation was greater than delays after arriving at hospital. Surgery without revascularization was the most common management approach. Nearly half of the patients with AMI died during their index hospitalization. Together, these findings suggest a need for greater awareness of AMI, and better guidance in diagnosis and management. TRIAL REGISTRATION: NCT05218863 (registered 19.01.2022).

Diagnostic accuracy of biomarkers to detect acute mesenteric ischaemia in adult patients: a systematic review and meta-analysis.

BACKGROUND: Acute mesenteric ischaemia (AMI) is a disease with different pathophysiological mechanisms, leading to a life-threatening condition that is difficult to diagnose based solely on clinical signs. Despite widely acknowledged need for biomarkers in diagnosis of AMI, a broad systematic review on all studied biomarkers in different types of AMI is currently lacking. The aim of this study was to estimate the diagnostic accuracy of all potential biomarkers of AMI studied in humans. METHODS: A systematic literature search in PubMed, The Cochrane Library, Web of Science and Scopus was conducted in December 2022. Studies assessing potential biomarkers of AMI in (at least 10) adult patients and reporting their diagnostic accuracy were included. Meta-analyses of biomarkers' sensitivity, specificity, and positive and negative likelihood ratios were conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the study quality was assessed with the QUADAS-2 tool. RESULTS: Seventy-five studies including a total of 9914 patients assessed 18 different biomarkers in serum/plasma and one in urine (each reported in at least two studies), which were included in meta-analyses. None of the biomarkers reached a conclusive level for accurate prediction. The best predictive value overall (all studies with any type and stage of AMI pooled) was observed for Ischaemia-modified albumin (2 studies, sensitivity 94.7 and specificity 90.5), interleukin-6 (n = 4, 96.3 and 82.6), procalcitonin (n = 6, 80.1 and 86.7), and intestinal fatty acid-binding protein (I-FABP) measured in serum (n = 16, 73.9 and 90.5) or in urine (n = 4, 87.9 and 78.9). In assessment of transmural mesenteric ischaemia, urinary I-FABP (n = 2, 92.3 and 85.2) and D-dimer (n = 3, 87.6 and 83.6) showed moderate predictive value. Overall risk of bias was high, mainly because of selected study populations and unclear timings of the biomarker measurements after onset of symptoms. Combinations of biomarkers were rarely studied, not allowing meta-analyses. CONCLUSIONS: None of the studied biomarkers had sufficient sensitivity and specificity to diagnose AMI, although some biomarkers showed moderate predictive accuracy. Future studies should focus on timing of measurements of biomarkers, distinguishing between early stage and transmural necrosis, and between different types of AMI. Additionally, studies on combinations of biomarkers are warranted. PROSPERO registration: CRD42022379341.

Epidemiology of Acute Mesenteric Ischemia: A Population-Based Investigation.

BACKGROUND: There is a lack of population-based studies on acute mesenteric ischemia (AMI). We have therefore performed a nationwide epidemiological study in Estonia, addressing incidence, demographics, interventions and mortality of AMI. METHODS: A retrospective population-based review was conducted of all adult cases of AMI accrued from the digital Estonian Health Insurance Fund and Causes of Death Registry for 2016-2020 based on international classification of diseases (ICD-10) diagnostic codes and procedure codes (NOMESCO). RESULTS: Overall, 577 cases of AMI were identified-an annual incidence of 8.7 per 100,000. The median age was 79 (range 32-104) and 57% were female. Predominating comorbidities included hypertensive disease (81%), atherosclerosis (67%), and atrial fibrillation (52%). The majority of cases (60%) were caused by superior mesenteric artery occlusion (thrombosis 54%, embolism 12%, and unclear 34%). Inferior mesenteric artery occlusion occurred in 7%, non-occlusive mesenteric ischemia in 7%, venous thrombosis in 4%, whereas the type remained unclear in 21% of cases. 40% of patients received intervention (revascularization and/or intestinal resection) and 13% active non-operative treatment. In 21% an exploratory laparotomy or laparoscopy revealed unsalvageable bowel prompting end-of-life care, which was the only management in a further 25% of cases. CONCLUSIONS: The population-based annual incidence of AMI in Estonia was 8.7 per 100,000 during the study period. The overall hospital mortality and 1 year mortality were 64% and 74%, respectively. In the 53% of patients who received active treatment hospital mortality was 32% and 1 year all-cause mortality was 51%. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04867499.

Incidence and outcomes of acute mesenteric ischaemia: a systematic review and meta-analysis.

OBJECTIVE: To estimate the incidence of acute mesenteric ischaemia (AMI), proportions of its different forms and short-term and long-term mortality. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE (Ovid), Web of Science, Scopus and Cochrane Library were searched until 26 July 2022. ELIGIBILITY CRITERIA: Studies reporting data on the incidence and outcomes of AMI in adult populations. DATA EXTRACTION AND SYNTHESIS: Data extraction and quality assessment with modified Newcastle-Ottawa scale were performed using predeveloped standard forms. The outcomes were the incidence of AMI and its different forms in the general population and in patients admitted to hospital, and the mortality of AMI in its different forms. RESULTS: From 3064 records, 335 full texts were reviewed and 163 included in the quantitative analysis. The mean incidence of AMI was 6.2 (95% CI 1.9 to 12.9) per 100 000 person years. On average 5.0 (95% CI 3.3 to 7.1) of 10 000 hospital admissions were due to AMI. Occlusive arterial AMI was the most common form constituting 68.6% (95% CI 63.7 to 73.2) of all AMI cases, with similar proportions of embolism and thrombosis.Overall short-term mortality (in-hospital or within 30 days) of AMI was 59.6% (95% CI 55.5 to 63.6), being 68.7% (95% CI 60.8 to 74.9) in patients treated before the year 2000 and 55.0% (95% CI 45.5 to 64.1) in patients treated from 2000 onwards (p<0.05). The mid/long-term mortality of AMI was 68.2% (95% CI 60.7 to 74.9). Mortality due to mesenteric venous thrombosis was 24.6% (95% CI 17.0 to 32.9) and of non-occlusive mesenteric ischaemia 58.4% (95% CI 48.6 to 67.7). The short-term mortality of revascularised occlusive arterial AMI was 33.9% (95% CI 30.7 to 37.4). CONCLUSIONS: In adult patients, AMI is a rarely diagnosed condition with high mortality, although with improvement of treatment results over the last decades. Two thirds of AMI cases are of occlusive arterial origin with potential for better survival if revascularised. PROSPERO REGISTRATION NUMBER: CRD42021247148.

Development of the Gastrointestinal Dysfunction Score (GIDS) for critically ill patients - A prospective multicenter observational study (iSOFA study).

BACKGROUND & AIMS: To develop a five grade score (0-4 points) for the assessment of gastrointestinal (GI) dysfunction in adult critically ill patients. METHODS: This prospective multicenter observational study enrolled consecutive adult patients admitted to 11 intensive care units in nine countries. At all sites, daily clinical data with emphasis on GI clinical symptoms were collected and intra-abdominal pressure measured. In five out of 11 sites, the biomarkers citrulline and intestinal fatty acid-binding protein (I-FABP) were measured additionally. Cox models with time-dependent scores were used to analyze associations with 28- and 90-day mortality. The models were estimated with stratification for study center. RESULTS: We included 540 patients (224 with biomarker measurements) with median age of 65 years (range 18-94), the Simplified Acute Physiology Score II score of 38 (interquartile range 26-53) points, and Sequential Organ Failure Assessment (SOFA) score of 6 (interquartile range 3-9) points at admission. Median ICU length of stay was 3 (interquartile range 1-6) days and 90-day mortality 18.9%. A new five grade Gastrointestinal Dysfunction Score (GIDS) was developed based on the rationale of the previously developed Acute GI Injury (AGI) grading. Citrulline and I-FABP did not prove their potential for scoring of GI dysfunction in critically ill. GIDS was independently associated with 28- and 90-day mortality when added to SOFA total score (HR 1.40; 95%CI 1.07-1.84 and HR 1.40; 95%CI 1.02-1.79, respectively) or to a model containing all SOFA subscores (HR 1.48; 95%CI 1.13-1.92 and HR 1.47; 95%CI 1.15-1.87, respectively), improving predictive power of SOFA score in all analyses. CONCLUSIONS: The newly developed GIDS is additive to SOFA score in prediction of 28- and 90-day mortality. The clinical usefulness of this score should be validated prospectively. TRIAL REGISTRATION: NCT02613000, retrospectively registered 24 November 2015.

Intra-abdominal hypertension and hypoxic respiratory failure together predict adverse outcome - A sub-analysis of a prospective cohort.

PURPOSE: To assess whether the combination of intra-abdominal hypertension (IAH, intra-abdominal pressure ≥ 12 mmHg) and hypoxic respiratory failure (HRF, PaO2/FiO2 ratio < 300 mmHg) in patients receiving invasive ventilation is an independent risk factor for 90- and 28-day mortality as well as ICU- and ventilation-free days. METHODS: Mechanically ventilated patients who had blood gas analyses performed and intra-abdominal pressure measured, were included from a prospective cohort. Subgroups were defined by the absence (Group 1) or the presence of either IAH (Group 2) or HRF (Group 3) or both (Group 4). Mixed-effects regression analysis was performed. RESULTS: Ninety-day mortality increased from 16% (Group 1, n = 50) to 30% (Group 2, n = 20) and 27% (Group 3, n = 100) to 49% (Group 4, n = 142), log-rank test p < 0.001. The combination of IAH and HRF was associated with increased 90- and 28-day mortality as well as with fewer ICU- and ventilation-free days. The association with 90-day mortality was no longer present after adjustment for independent variables. However, the association with 28-day mortality, ICU- and ventilation-free days persisted after adjusting for independent variables. CONCLUSIONS: In our sub-analysis, the combination of IAH and HRF was not independently associated with 90-day mortality but independently increased the odds of 28-day mortality, and reduced the number of ICU- and ventilation-free days.

Hypophosphatemia in critically ill adults and children - A systematic review.

BACKGROUND & AIMS: Phosphate is the main intracellular anion essential for numerous biological processes. Symptoms of hypophosphatemia are non-specific, yet potentially life-threatening. This systematic review process was initiated to gain a global insight into hypophosphatemia, associated morbidity and treatments. METHODS: A systematic review was conducted (PROSPERO CRD42020163191). Nine clinically relevant questions were generated, seven for adult and two for pediatric critically ill patients, and prevalence of hypophosphatemia was assessed in both groups. We identified trials through systematic searches of Medline, EMBASE, Scopus, Cochrane Central Register of Controlled Trials, CINAHL, and Web of Science. Quality assessment was performed using the Cochrane risk of bias tool for randomized controlled trials and the Newcastle-Ottawa Scale for observational studies. RESULTS: For all research questions, we identified 2727 titles in total, assessed 399 full texts, and retained 82 full texts for evidence synthesis, with 20 of them identified for several research questions. Only 3 randomized controlled trials were identified with two of them published only in abstract form, as well as 28 prospective and 31 retrospective studies, and 20 case reports. Relevant risk of bias regarding selection and comparability was identified for most of the studies. No meta-analysis could be performed. The prevalence of hypophosphatemia varied substantially in critically ill adults and children, but no study assessed consecutive admissions to intensive care. In both critically ill adults and children, several studies report that hypophosphatemia is associated with worse outcome (prolonged length of stay and the need for respiratory support, and higher mortality). However, there was insufficient evidence regarding the optimal threshold upon which hypophosphatemia becomes critical and requires treatment. We found no studies regarding the optimal frequency of phosphate measurements, and regarding the time window to correct hypophosphatemia. In adults, nutrient restriction on top of phosphate repletion in patients with refeeding syndrome may improve survival, although evidence is weak. CONCLUSIONS: Evidence on the definition, outcome and treatment of clinically relevant hypophosphatemia in critically ill adults and children is scarce and does not allow answering clinically relevant questions. High quality clinical research is crucial for the development of respective guidelines.

Diarrhea and elevation of plasma markers of cholestasis are common and often occur concomitantly in critically ill patients.

PURPOSE: We aimed to describe epidemiology of diarrhea and cholestasis in critically ill patients and explore associations between these two conditions. MATERIAL AND METHODS: We performed a retrospective study including all consecutive patients who stayed in the ICU for at least 3 days and in whom plasma measurements of liver enzymes/cholestasis parameters were performed. Diarrhea was defined as 3 or more loose or liquid stools per day and cholestasis as increase of alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GGT) 1.5 times above the upper limit of normality. RESULTS: Diarrhea was observed in 26.1% and cholestasis in 27.9% of study patients, about one third of the cases in both diarrhea and cholestasis occurred beyond the first week of patient's ICU stay. Cholestasis occurred in 45.6% of patients with diarrhea vs 28.0% of patients without diarrhea (p < 0.001). In 94 patients (13.1%) both diarrhea and cholestasis occurred, cholestasis was more commonly (2/3 of cases) documented before manifestation of diarrhea. CONCLUSIONS: Cholestasis is more common in patients with diarrhea and vice versa. Diarrhea and cholestasis both occur in approximately one quarter of ICU patients, with significant proportion manifesting beyond the first week in the ICU.

Dosing of Ertapenem in an Extreme Obesity: A Case Report of 250 kg Patient.

Limited available data for dosing in obesity of the medicines used in this case are discussed, with the emphasis on ertapenem. The case illustrates the difficulties in dosing medicines to morbidly overweight patients. The number of such patients is increasing but data on adequate doses of medicines are scarce. We demonstrate that ertapenem 1,5 g i.v. once daily provided adequate drug exposure for susceptible bacteria in a 250 kg patient with normal renal function. The case suggests the usefulness of therapeutic drug monitoring of antibiotics, especially in critically ill patients.

Effects of high volume haemodiafiltration on inflammatory response profile and microcirculation in patients with septic shock.

BACKGROUND: High volumes of haemofiltration are used in septic patients to control systemic inflammation and improve patient outcomes. We aimed to clarify if extended intermittent high volume online haemodiafiltration (HVHDF) influences patient haemodynamics and cytokines profile and/or has effect upon sublingual microcirculation in critically ill septic shock patients. METHODS: Main haemodynamic and clinical variables and concentrations of cytokines were evaluated before and after HVHDF in 19 patients with septic shock requiring renal replacement therapy due to acute kidney injury. Sublingual microcirculation was assessed in 9 patients. RESULTS: The mean (SD) time of HVHDF was 9.4 (1.8) hours. The median convective volume was 123 mL/kg/h. The mean (SD) dose of norepinephrine required to maintain mean arterial pressure at the target range of 70-80 mmHg decreased from 0.40 (0.43) µg/kg/min to 0.28 (0.33) µg/kg/min (p = 0.009). No significant changes in the measured cytokines or microcirculatory parameters were observed before and after HVHDF. CONCLUSIONS: The single-centre study suggests that extended HVHDF results in decrease of norepinephrine requirement in patients with septic shock. Haemodynamic improvement was not associated with decrease in circulating cytokine levels, and sublingual microcirculation was well preserved.

Pharmacokinetics of doripenem during high volume hemodiafiltration in patients with septic shock.

Pharmacokinetics (PK) of doripenem was determined during high volume hemodiafiltration (HVHDF) in patients with septic shock. A single 500 mg dose of doripenem was administered as a 1 hour infusion during HVHDF to 9 patients. Arterial blood samples were collected before and at 30 or 60 minute intervals over 8 hours (12 samples) after study drug administration. Doripenem concentrations were determined by ultrahigh performance liquid chromatography-tandem mass spectrometry. Population PK analysis and Monte Carlo simulation of 1,000 subjects were performed. The median convective volume of HVHDF was 10.3 L/h and urine output during the sampling period was 70 mL. The population mean total doripenem clearance on HVHDF was 6.82 L/h, volume of distribution of central compartment 10.8 L, and of peripheral compartment 12.1 L. Doses of 500 mg every 8 hours resulted in 88.5% probability of attaining the target of 50% time over MIC for bacteria with MIC = 2 µg/mL at 48 hours, when doubling of MIC during that time was assumed. Significant elimination of doripenem occurs during HVHDF. Doses of 500 mg every 8 hours are necessary for treatment of infections caused by susceptible bacteria during extended HVHDF.

Expanded measurements of intra-abdominal pressure do not increase the detection rate of intra-abdominal hypertension: a single-center observational study.

OBJECTIVE: Intra-abdominal hypertension may contribute to a poor outcome. Whether limiting intra-abdominal pressure measurements to preselected at-risk patients allows for sufficient detection of intra-abdominal hypertension is unclear. We aimed to clarify whether expanded intra-abdominal pressure monitoring results in an increased detection rate of intra-abdominal hypertension. DESIGN: Retrospective observational study. SETTING: General ICU of University Hospital. PATIENTS: Consecutive adult ICU patients from 2004 to 2011. INTERVENTIONS: Intra-abdominal pressure measurements in predefined at-risk patients. MEASUREMENTS AND MAIN RESULTS: Prospectively collected data of 2,696 admissions were divided into three subgroups according to the intra-abdominal pressure measurement policy in different years: 1) 2004-2005, mechanically ventilated patients with at least one additional risk factor for intra-abdominal hypertension (multiple trauma, abdominal surgery, pancreatitis, post-cardiopulmonary resuscitation, fluid resuscitation > 5 L/24 hr, vasoactive or inotropic support, and renal replacement therapy); 2) 2006-2009, all mechanically ventilated patients expected to stay for more than or equal to 24 hours; and 3) 2010-2011, mechanically ventilated patients with a body mass index greater than 30 kg/m, positive end-expiratory pressure more than 10 cm H2O, PaO2/FIO2 less than 300, use of vasopressors/inotropes, pancreatitis, hepatic failure/cirrhosis with ascites, gastrointestinal bleeding, or postlaparotomy. In all, 2,696 patients were studied, and 1,241 patients (46.0%) underwent intra-abdominal pressure monitoring. The intra-abdominal pressure was measured in 31.7%, 55.6%, and 41.1% of patients during the first, second, and third time periods (p < 0.001), and intra-abdominal hypertension (intra-abdominal pressure ≥ 12 mm Hg) occurred in 19.9%, 20.3%, and 20.1% of patients, respectively (p = 0.972). The mean intra-abdominal pressure at admission day was an independent predictor of mortality in patients with intra-abdominal pressure measurements started within the first 24 hours (odds ratio, 1.046 [95% CI, 1.019-1.072]). The mortality of patients with intra-abdominal hypertension was 29.8% versus 18.6% in those without intra-abdominal hypertension (p < 0.001). CONCLUSIONS: Expanding the measurement of intra-abdominal pressure to more than 50% of intensive care admissions does not increase the detection rate of intra-abdominal hypertension. In patients with intra-abdominal pressure monitoring, the mean intra-abdominal pressure on the admission day is an independent predictor of mortality.

Should we measure intra-abdominal pressures in every intensive care patient?

Intra-abdominal pressure (IAP) is seldom measured by default in intensive care patients. This review summarises the current evidence on the prevalence and risk factors of intra-abdominal hypertension (IAH) to assist the decision-making for IAP monitoring.IAH occurs in 20% to 40% of intensive care patients. High body mass index (BMI), abdominal surgery, liver dysfunction/ascites, hypotension/vasoactive therapy, respiratory failure and excessive fluid balance are risk factors of IAH in the general ICU population. IAP monitoring is strongly supported in mechanically ventilated patients with severe burns, severe trauma, severe acute pancreatitis, liver failure or ruptured aortic aneurysms. The risk of developing IAH is minimal in mechanically ventilated patients with positive end-expiratory pressure < 10 cmH2O, PaO2/FiO2 > 300, and BMI < 30 and without pancreatitis, hepatic failure/cirrhosis with ascites, gastrointestinal bleeding or laparotomy and the use of vasopressors/inotropes on admission. In these patients, omitting IAP measurements might be considered.In conclusions, clear guidelines to select the patients in whom IAP measurements should be performed cannot be given at present. In addition to IAP measurements in at-risk patients, a clinical assessment of the signs of IAH should be a part of every ICU patient's bedside evaluation, leading to prompt IAP monitoring in case of the slightest suspicion of IAH development.

Two cases of takotsubo syndrome related to tracheal intubation/extubation.

Takotsubo cardiomyopathy is an acute, reversible left ventricular dysfunction with characteristic contractility disorder and is usually preceded by emotional or physical stress. Two cases of Takotsubo cardiomyopathy related to tracheal manipulation are presented. Both the patients had all the typical symptoms and signs of Takotsubo cardiomyopathy, and both of them recovered completely within weeks. Tracheal manipulation is a well-known stress factor during the perioperative period, and experience from these two cases stresses the crucial role of measures aimed to stress reduction. Proper premedication and calm environment are recommended to produce anxiolysis before intubation. The administration of α- and ß-blockers is also recommended to inhibit sympathetic stress caused by tracheal manipulation.

Clinical and pathological findings of fatal 2009-2010 pandemic influenza A (H1N1) infection in Estonia.

The aim of this study was to analyze all deaths from A (H1N1) in Estonia during the 2009-2010 epidemic to find out the reasons of high mortality and optimize management strategies for future influenza epidemics. MATERIAL AND METHODS. A retrospective review of medical records, autopsy reports, and reassessment of autopsy slides of all fatal cases of proven A (H1N1) influenza in Estonia from October 2009 to May 2010 was carried out. RESULTS. There were a total of 21 proven fatal cases (median age, 57 years); the population mortality rate of 1.56 per 100 000 inhabitants was one of the highest in the world. Altogether, 18 of the 21 patients had known risk factors for influenza, and 3 patients were previously healthy children. Three decedents had received antiviral treatment, and none had been immunized. There were 19 decedents autopsied, with viral pneumonia (58%) being the most frequent pathological finding; 40% had evidence of bacterial superinfection. In 4 cases, influenza was not clinically suspected and was diagnosed postmortem. Influenza was the primary cause of death in 15 decedents, while in 9 cases, comorbidities played a significant role in fatal outcome. In the remaining 4 cases, another illness was considered the primary cause of death with influenza as an accompanying factor. CONCLUSIONS. High autopsy rate and liberal postmortem PCR testing enables the detection of additional A (H1N1) influenza cases, yet it might lead to overestimation of the population mortality rates, especially in a small population with low number of events. Increased vaccine coverage, vigilant diagnosing including wide PCR testing, and early more liberal use of antiviral medications during the influenza A (H1N1) epidemic may hold the potential of lowering population mortality.

Successful liver transplantation after 21 days of hepatic coma.

A 52-year-old women was treated after ingestion of different wild mushrooms. The case demonstrates that successful liver transplantation with full recovery of brain functions is possible even after 3 weeks of persisting severe hepatic encephalopathy.