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).

Variation in Severity-Adjusted Resource use and Outcome for Neurosurgical Emergencies in the Intensive Care Unit.

BACKGROUND: The correlation between the standardized resource use ratio (SRUR) and standardized hospital mortality ratio (SMR) for neurosurgical emergencies is not known. We studied SRUR and SMR and the factors affecting these in patients with traumatic brain injury (TBI), nontraumatic intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). METHODS: We extracted data of patients treated in six university hospitals in three countries (2015-2017). Resource use was measured as SRUR based on purchasing power parity-adjusted direct costs and either intensive care unit (ICU) length of stay (costSRURlength of stay) or daily Therapeutic Intervention Scoring System scores (costSRURTherapeutic Intervention Scoring System). Five a priori defined variables reflecting differences in structure and organization between the ICUs were used as explanatory variables in bivariable models, separately for the included neurosurgical diseases. RESULTS: Out of 28,363 emergency patients treated in six ICUs, 6,162 patients (22%) were admitted with a neurosurgical emergency (41% nontraumatic ICH, 23% SAH, 13% multitrauma TBI, and 23% isolated TBI). The mean costs for neurosurgical admissions were higher than for nonneurosurgical admissions, and the neurosurgical admissions corresponded to 23.6-26.0% of all direct costs related to ICU emergency admissions. A higher physician-to-bed ratio was associated with lower SMRs in the nonneurosurgical admissions but not in the neurosurgical admissions. In patients with nontraumatic ICH, lower costSRURs were associated with higher SMRs. In the bivariable models, independent organization of an ICU was associated with lower costSRURs in patients with nontraumatic ICH and isolated/multitrauma TBI but with higher SMRs in patients with nontraumatic ICH. A higher physician-to-bed ratio was associated with higher costSRURs for patients with SAH. Larger units had higher SMRs for patients with nontraumatic ICH and isolated TBI. None of the ICU-related factors were associated with costSRURs in nonneurosurgical emergency admissions. CONCLUSIONS: Neurosurgical emergencies constitute a major proportion of all emergency ICU admissions. A lower SRUR was associated with higher SMR in patients with nontraumatic ICH but not for the other diagnoses. Different organizational and structural factors seemed to affect resource use for the neurosurgical patients compared with nonneurosurgical patients. This emphasizes the importance of case-mix adjustment when benchmarking resource use and outcomes.

Biomarkers In Prediction of Acute Mesenteric Ischaemia: a prospective multicentre study (BIPAMI study): a study protocol.

BACKGROUND: Acute mesenteric ischaemia (AMI) is a life-threatening disease where early diagnosis is critical to avoid morbidity and mortality from extensive irreversible bowel necrosis. Appropriate prediction of presence of bowel necrosis is currently not available but would help to choose the optimal method of treatment. The study aims to identify combinations of biomarkers that can reliably identify AMI and distinguish between potentially reversible and irreversible bowel ischaemia. METHODS: This is a prospective multicentre study. Adult patients with clinical suspicion of AMI (n = 250) will be included. Blood will be sampled on admission, at and after interventions, or during the first 48 h of suspicion of AMI if no intervention undertaken. Samples will be collected and the following serum or plasma biomarkers measured at Tartu University Hospital laboratory: intestinal fatty acid-binding protein (I-FABP), alpha-glutathione S-transferase (Alpha- GST), interleukin 6 (IL-6), procalcitonin (PCT), ischaemia-modified albumin (IMA), D-lactate, D-dimer, signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1) and lipopolysaccharide-binding protein (LBP). Additionally, more common laboratory markers will be measured in routine clinical practice at study sites. Diagnosis of AMI will be confirmed by computed tomography angiography, surgery, endoscopy or autopsy. Student's t or Wilcoxon rank tests will be used for comparisons between transmural vs. suspected (but not confirmed) AMI (comparison A), confirmed AMI of any stage vs suspected AMI (comparison B) and non-transmural AMI vs transmural AMI (comparison C). Optimal cut-off values for each comparison will be identified based on the AUROC analysis and likelihood ratios calculated. Positive likelihood ratio > 10 (> 5) and negative likelihood ratio < 0.1 (< 0.2) indicate high (moderate) diagnostic accuracy, respectively. All biomarkers with at least moderate accuracy will be entered as binary covariates (using the best cutoffs) into the multivariable stepwise regression analysis to identify the best combination of biomarkers for all comparisons separately. The best models for each comparison will be used to construct a practical score to distinguish between no AMI, non-transmural AMI and transmural AMI. DISCUSSION: As a result of this study, we aim to propose a score including set of biomarkers that can be used for diagnosis and decision-making in patients with suspected AMI. TRIAL REGISTRATION: NCT06212921 (Registration Date 19-01-2024).

Population pharmacokinetics and pharmacodynamics of dobutamine in neonates on the first days of life.

AIMS: To describe the pharmacokinetics (PK) and concentration-related effects of dobutamine in critically ill neonates in the first days of life, using nonlinear mixed effects modelling. METHODS: Dosing, plasma concentration and haemodynamic monitoring data from a dose-escalation study were analysed with a simultaneous population PK and pharmacodynamic model. Neonates receiving continuous infusion of dobutamine 5-20 µg kg-1 min-1 were included. Left ventricular ejection fraction (LVEF) and cardiac output of right and left ventricle (RVO, LVO) were measured on echocardiography; heart rate (HR), mean arterial pressure (MAP), peripheral arterial oxygen saturation and cerebral regional oxygen saturation were recorded from patient monitors. RESULTS: Twenty-eight neonates with median (range) gestational age of 30.4 (22.7-41.0) weeks and birth weight (BW) of 1618 (465-4380) g were included. PK data were adequately described by 1-compartmental linear structural model. Dobutamine clearance (CL) was described by allometric scaling on BW with sigmoidal maturation function of postmenstrual age (PMA). The final population PK model parameter mean typical value (standard error) estimates, standardised to median BW of 1618 g, were 41.2 (44.5) L h-1 for CL and 5.29 (0.821) L for volume of distribution, which shared a common between subject variability of 29% (17.2%). The relationship between dobutamine concentration and RVO/LVEF was described by linear model, between concentration and LVO/HR/MAP/cerebral fractional tissue oxygen extraction by sigmoidal Emax model. CONCLUSION: In the postnatal transitional period, PK of dobutamine was described by a 1-compartmental linear model, CL related to BW and PMA. A concentration-response relationship with haemodynamic variables has been established.

Remote Ischaemic Preconditioning Attenuates Cardiac Biomarkers During Vascular Surgery: A Randomised Clinical Trial.

OBJECTIVE: The main aim of this study was to evaluate the effect of remote ischaemic preconditioning (RIPC) on preventing the leakage of cardiac damage biomarkers in patients undergoing vascular surgery. METHODS: This is a randomised, sham-controlled, double-blinded, single-centre study. Patients undergoing open abdominal aortic aneurysm repair, surgical lower limb revascularisation surgery or carotid endarterectomy were recruited non-consecutively. The RIPC protocol consisting of 4 cycles of 5 minutes of ischaemia, followed by 5 minutes of reperfusion, was applied. A RIPC or a sham procedure was performed noninvasively along with preparation for anaesthesia. High sensitivity troponin T level was measured preoperatively and 2, 8 and 24 hours after surgery and pro b-type natriuretic peptide was measured preoperatively and 24 hours after surgery. RESULTS: There was significantly higher leakage of high sensitivity troponin T (peak change median 2 ng/L, IQR 0.9-6.2 ng/L vs 0.6 ng/L, IQR 0.7-2.1 ng/L, p = .0002) and pro b-type natriuretic peptide (change median 144 pg/mL, IQR 17-318 pg/mL vs 51 pg/mL, IQR 12-196 pg/mL, p = .02) in the sham group compared to the RIPC group. CONCLUSION: RIPC reduces the leakage of high sensitivity troponin T and pro b-type natriuretic peptide. Therefore, it may offer cardioprotection in patients undergoing non-cardiac vascular surgery. The clinical significance of RIPC has to be evaluated in larger studies excluding the factors known to influence its effect.

Gastrointestinal dysfunction in the critically ill: a systematic scoping review and research agenda proposed by the Section of Metabolism, Endocrinology and Nutrition of the European Society of Intensive Care Medicine.

BACKGROUND: Gastrointestinal (GI) dysfunction is frequent in the critically ill but can be overlooked as a result of the lack of standardization of the diagnostic and therapeutic approaches. We aimed to develop a research agenda for GI dysfunction for future research. We systematically reviewed the current knowledge on a broad range of subtopics from a specific viewpoint of GI dysfunction, highlighting the remaining areas of uncertainty and suggesting future studies. METHODS: This systematic scoping review and research agenda was conducted following successive steps: (1) identify clinically important subtopics within the field of GI function which warrant further research; (2) systematically review the literature for each subtopic using PubMed, CENTRAL and Cochrane Database of Systematic Reviews; (3) summarize evidence for each subtopic; (4) identify areas of uncertainty; (5) formulate and refine study proposals that address these subtopics; and (6) prioritize study proposals via sequential voting rounds. RESULTS: Five major themes were identified: (1) monitoring, (2) associations between GI function and outcome, (3) GI function and nutrition, (4) management of GI dysfunction and (5) pathophysiological mechanisms. Searches on 17 subtopics were performed and evidence summarized. Several areas of uncertainty were identified, six of them needing consensus process. Study proposals ranked among the first ten included: prevention and management of diarrhoea; management of upper and lower feeding intolerance, including indications for post-pyloric feeding and opioid antagonists; acute gastrointestinal injury grading as a bedside tool; the role of intra-abdominal hypertension in the development and monitoring of GI dysfunction and in the development of non-occlusive mesenteric ischaemia; and the effect of proton pump inhibitors on the microbiome in critical illness. CONCLUSIONS: Current evidence on GI dysfunction is scarce, partially due to the lack of precise definitions. The use of core sets of monitoring and outcomes are required to improve the consistency of future studies. We propose several areas for consensus process and outline future study projects.

Incidence, Risk Factors, and Outcomes of Intra-Abdominal Hypertension in Critically Ill Patients-A Prospective Multicenter Study (IROI Study).

OBJECTIVES: To identify the prevalence, risk factors, and outcomes of intra-abdominal hypertension in a mixed multicenter ICU population. DESIGN: Prospective observational study. SETTING: Fifteen ICUs worldwide. PATIENTS: Consecutive adult ICU patients with a bladder catheter. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four hundred ninety-one patients were included. Intra-abdominal pressure was measured a minimum of every 8 hours. Subjects with a mean intra-abdominal pressure equal to or greater than 12 mm Hg were defined as having intra-abdominal hypertension. Intra-abdominal hypertension was present in 34.0% of the patients on the day of ICU admission (159/467) and in 48.9% of the patients (240/491) during the observation period. The severity of intra-abdominal hypertension was as follows: grade I, 47.5%; grade II, 36.6%; grade III, 11.7%; and grade IV, 4.2%. The severity of intra-abdominal hypertension during the first 2 weeks of the ICU stay was identified as an independent predictor of 28- and 90-day mortality, whereas the presence of intra-abdominal hypertension on the day of ICU admission did not predict mortality. Body mass index, Acute Physiology and Chronic Health Evaluation II score greater than or equal to 18, presence of abdominal distension, absence of bowel sounds, and positive end-expiratory pressure greater than or equal to 7 cm H2O were independently associated with the development of intra-abdominal hypertension at any time during the observation period. In subjects without intra-abdominal hypertension on day 1, body mass index combined with daily positive fluid balance and positive end-expiratory pressure greater than or equal to 7 cm H2O (as documented on the day before intra-abdominal hypertension occurred) were associated with the development of intra-abdominal hypertension during the first week in the ICU. CONCLUSIONS: In our mixed ICU patient cohort, intra-abdominal hypertension occurred in almost half of all subjects and was twice as prevalent in mechanically ventilated patients as in spontaneously breathing patients. Presence and severity of intra-abdominal hypertension during the observation period significantly and independently increased 28- and 90-day mortality. Five admission day variables were independently associated with the presence or development of intra-abdominal hypertension. Positive fluid balance was associated with the development of intra-abdominal hypertension after day 1.

Translating the European Society for Clinical Nutrition and Metabolism 2019 guidelines into practice.

PURPOSE OF REVIEW: To present a pragmatic approach to facilitate clinician's implementing the recent European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines on clinical nutrition in the intensive care unit. RECENT FINDINGS: The ESPEN guidelines include 54 recommendations with a rationale for each recommendation. All data published since 1 January 2000 was reviewed and 31 meta-analyses were performed to inform these guidelines. An important aspect of the most recent ESPEN guidelines is an attempt to separate periods of critical illness into discrete - early acute, late acute and recovery - phases, with each exhibiting different metabolic profiles and requiring different strategies for nutritional and metabolic support. SUMMARY: A pragmatic approach to incorporate the recent ESPEN guidelines into everyday clinical practice is provided.

The Effect of Remote Ischaemic Preconditioning on Arterial Stiffness in Patients Undergoing Vascular Surgery: A Randomised Clinical Trial.

OBJECTIVES: The main aim of this study was to evaluate the effect of remote ischaemic preconditioning (RIPC) on arterial stiffness in patients undergoing vascular surgery. METHODS: This was a randomised, sham controlled, double blind, single centre study. Patients undergoing open abdominal aortic aneurysm repair, surgical lower limb revascularisation surgery or carotid endarterectomy were recruited. A RIPC or a sham procedure was performed, using a blood pressure cuff, along with preparation for anaesthesia. The RIPC protocol consisting of four cycles of 5 min of ischaemia, followed by 5 min of reperfusion was applied. Arterial stiffness and haemodynamic parameters were measured pre-operatively and 20-28 h after surgery. Two primary outcomes were selected: augmentation index and pulse wave velocity. RESULTS: Ninety-eight patients were randomised. After dropouts 44 and 46 patients were included in the RIPC and sham groups, respectively. Both groups were comparable. There were no statistically significant differences in augmentation index (p = .8), augmentation index corrected for heart rate of 75 beats per minute (p = .8), pulse wave velocity (p = .7), large artery elasticity indices (p = .8), small artery elasticity indices (p = .6), or mean arterial pressure (p = .7) changes between the RIPC and sham groups. There occurred statistically significant (p ≤ .01) improvement in augmentation index (-5.8% vs. -5.5%), augmentation index corrected for a heart rate of 75 beats per minute (-2.5% vs. -2%), small artery elasticity indices (0.7 mL/mmHg × 100 vs. 0.9 mL/mmHg × 100), and mean arterial pressure post-operatively in both the RIPC and the sham groups (change median values in RIPC and sham groups, respectively). CONCLUSIONS: RIPC had no significant effect on arterial stiffness, but there was significant improvement in arterial stiffness after surgery in both groups. Arterial stiffness and haemodynamics may be influenced by surgery or anaesthesia or oxidative stress or all factors combined. Further studies are needed to clarify these findings. CLINICALTRIALS.GOV: NCT02689414.

Population Pharmacokinetics and Dosing of Milrinone After Patent Ductus Arteriosus Ligation in Preterm Infants.

OBJECTIVES: The postoperative course of patent ductus arteriosus ligation is often complicated by postligation cardiac syndrome, occurring in 10-45% of operated infants. Milrinone might prevent profound hemodynamic instability and improve the recovery of cardiac function in this setting. The present study aimed to describe the population pharmacokinetics of milrinone in premature neonates at risk of postligation cardiac syndrome and give dosing recommendations. DESIGN: A prospective single group open-label pharmacokinetics study. SETTINGS: Two tertiary care neonatal ICUs: Tallinn Children's Hospital and Tartu University Hospital, Estonia. PATIENTS: Ten neonates with postmenstrual age of 24.6-30.1 weeks and postnatal age of 5-27 days undergoing patent ductus arteriosus ligation and at risk of postligation cardiac syndrome, based on echocardiographic assessment of left ventricular output of less than 200 mL/kg/min 1 hour after the surgery. INTERVENTIONS: Milrinone at a dose of 0.73 µg/kg/min for 3 hours followed by 0.16 µg/kg/min for 21 hours. Four blood samples from each patient for milrinone plasma concentration measurements were collected. MEASUREMENTS AND MAIN RESULTS: Concentration-time data of milrinone were analyzed with nonlinear mixed-effects modeling software (NONMEM Version 7.3 [ICON Development Solutions, Ellicott City, MD]). Probability of target attainment simulations gave a dosing schedule that maximally attains concentration targets of 150-250 µg/L. Milrinone pharmacokinetics was described by a one-compartmental linear model with allometric scaling to bodyweight and an age maturation function of glomerular filtration rate. Parameter estimates for a patient with the median weight were 0.350 (L/hr) for clearance and 0.329 (L) for volume of distribution. The best probability of target attainment was achieved with a loading dose of 0.50 µg/kg/min for 3 hours followed by 0.15 µg/kg/min (postmenstrual age < 27 wk) or 0.20 µg/kg/min (postmenstrual age ≥ 27 wk). CONCLUSIONS: Population pharmacokinetic modeling and simulations suggest a slow loading dose followed by maintenance infusion to reach therapeutic milrinone plasma concentrations within the timeframe of the postligation cardiac syndrome.

Gastrointestinal failure in the ICU.

PURPOSE OF REVIEW: The current review summarizes different aspects of assessment of gastrointestinal function and provides a practical approach to management of adult patients with gastrointestinal dysfunction in the ICU. RECENT FINDINGS: Different ways to define gastrointestinal failure have been used in the past. Recently, the term 'acute gastrointestinal injury (AGI)' has been proposed to specifically describe gastrointestinal dysfunction as a part of multiple organ dysfunction syndrome. Possible pathophysiological mechanisms and different aspects in assessment of gastrointestinal function in adult ICU patients are presented. Currently, there is no single marker that could reliably describe gastrointestinal dysfunction. Therefore, monitoring and management is still based on complex assessment of different gastrointestinal symptoms and feeding intolerance, even though this approach includes a large amount of subjectivity. The possible role of biomarkers (citrulline, enterohormones, etc.) and additional parameters like intra-abdominal pressure remains to be clarified. SUMMARY: Defining gastrointestinal failure remains challenging but broad consensus needs to be reached and disseminated soon to allow conduct of interventional studies. A systematic approach to management of gastrointestinal problems is recommended.

Space GlucoseControl system for blood glucose control in intensive care patients--a European multicentre observational study.

BACKGROUND: Glycaemia control (GC) remains an important therapeutic goal in critically ill patients. The enhanced Model Predictive Control (eMPC) algorithm, which models the behaviour of blood glucose (BG) and insulin sensitivity in individual ICU patients with variable blood samples, is an effective, clinically proven computer based protocol successfully tested at multiple institutions on medical and surgical patients with different nutritional protocols. eMPC has been integrated into the B.Braun Space GlucoseControl system (SGC), which allows direct data communication between pumps and microprocessor. The present study was undertaken to assess the clinical performance and safety of the SGC for glycaemia control in critically ill patients under routine conditions in different ICU settings and with various nutritional protocols. METHODS: The study endpoints were the percentage of time the BG was within the target range 4.4 - 8.3 mmol.l(-1), the frequency of hypoglycaemic episodes, adherence to the advice of the SGC and BG measurement intervals. BG was monitored, and insulin was given as a continuous infusion according to the advice of the SGC. Nutritional management (enteral, parenteral or both) was carried out at the discretion of each centre. RESULTS: 17 centres from 9 European countries included a total of 508 patients, the median study time was 2.9 (1.9-6.1) days. The median (IQR) time-in-target was 83.0 (68.7-93.1) % of time with the mean proposed measurement interval 2.0 ± 0.5 hours. 99.6% of the SGC advices on insulin infusion rate were accepted by the user. Only 4 episodes (0.01% of all BG measurements) of severe hypoglycaemia <2.2 mmol.l(-1) in 4 patients occurred (0.8%; 95% CI 0.02-1.6%). CONCLUSION: Under routine conditions and under different nutritional protocols the Space GlucoseControl system with integrated eMPC algorithm has exhibited its suitability for glycaemia control in critically ill patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01523665.

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.

Postoperative complications and mortality after major gastrointestinal surgery.

BACKGROUND AND OBJECTIVE: The incidence of postoperative complications and death is low in the general population, but a subgroup of high-risk patients can be identified amongst whom adverse postoperative outcomes occur more frequently. The present study was undertaken to describe the incidence of postoperative complications, length of stay, and mortality after major abdominal surgery for gastrointestinal, hepatobiliary and pancreatic malignancies and to identify the risk factors for impaired outcome. MATERIAL AND METHODS: Data of patients, operated on for gastro-intestinal malignancies during 2009-2010 were retrieved from the clinical database of Tartu University Hospital. Major outcome data included incidence of postoperative complications, hospital-, 30-day, 90-day and 1-year mortality, and length of ICU and hospital stay. High-risk patients were defined as patients with American Society of Anesthesiologists (ASA) physical status ≥3 and revised cardiac risk index (RCRI) ≥3. Multivariate analysis was used to determine the risk factors for postoperative mortality and morbidity. RESULTS: A total of 507 (259 men and 248 women, mean age 68.3±11.3 years) were operated on for gastrointestinal, hepatobiliary, or pancreatic malignancies during 2009 and 2010 in Tartu University Hospital, Department of Surgical Oncology. 25% of the patients were classified as high risk patients. The lengths of intensive care and hospital stay were 4.4±7 and 14.5±10 days, respectively. The rate of postoperative complications was 33.5% in the total cohort, and 44% in high-risk patients. The most common complication was delirium, which occurred in 12.8% of patients. For patients without high risk (ASA130min, and positive fluid balance >1300mL after the 1st postoperative day, were identified as independent risk factors for the development of complications. CONCLUSION: The complication rate after major gastro-intestinal surgery is high. ASA physical status and revised cardiac risk index adequately reflect increased risk for postoperative complications and worse short and long-term outcome.

Prospective multicenter study to validate the Gastrointestinal Dysfunction Score (GIDS) in intensive care patients: Study protocol for Part A of the international GUTPHOS study.

BACKGROUND: While gastrointestinal (GI) dysfunction is commonly encountered among critically ill patients, a uniform prospectively validated scoring system is lacking. The present study aims to validate the recently developed Gastrointestinal Dysfunction Score (GIDS) in a multicenter, prospective cohort of consecutive adult patients admitted to intensive care units (ICU). METHODS: GUTPHOS is a prospective, multicenter, non-interventional cohort study in which at least 1400 consecutive adult patients (age ≥18 years) admitted to the ICU will be monitored daily for abdominal signs and symptoms of GI dysfunction. The previously developed GIDS constructed from these signs and symptoms will be tested in relation to mortality and duration of ICU dependency and parenteral nutrition (PN) dependency. Between January and June 2024, each participating clinical site will include 50-120 consecutive patients over an eight-week period. Study data will be collected in three phases: baseline data upon ICU admission, daily observations throughout a maximum of 7 days in ICU or until discharge, and a follow-up period of 90 days. The primary outcomes are 28- and 90-day all-cause mortality. Secondary outcomes include ICU and hospital mortality, ICU and hospital length of stay, days alive and free of ICU by day 28 and day 90, days alive and free of hospital by day 28 and day 90, and days alive and free of organ support and PN dependency by day 28. DISCUSSION: The GUTPHOS study will be the first worldwide, multicenter, prospective, observational cohort study to validate the GIDS in adult patients admitted to ICUs against 28- and 90-day mortality. The availability of a validated tool will allow its use in interventional studies that are currently hindered by the lack of a validated measurement tool for GI dysfunction. CLINICAL TRIAL REGISTRY: NCT05909722.

Prospective multicenter study to describe the prevalence, outcomes, and management of phosphate disorders in intensive care patients: Study protocol for Part B of the international GUTPHOS study.

BACKGROUND: Aberrations in blood phosphate (Pi) levels, whether presenting as hypo- or hyperphosphatemia, appear to be associated with clinical complications and adverse outcomes in patients admitted to an intensive care unit (ICU). However, the prevalence of Pi disorders and the association with subsequent factors and organ failures leading to death in ICU patients are poorly described. Despite endeavors to understand the etiology and treatment of low Pi levels from systematic reviews and meta-analyses, the literature lacks comprehensive guidance for managing hypophosphatemia. Hyperphosphatemia, on the other hand, appears to be associated with higher mortality among critically ill patients, yet its prevalence among ICU patients, particularly following phosphate repletion, remains unknown. The present study aims to investigate the prevalence of Pi abnormalities upon ICU admission and their incidence during the first week of ICU stay, the factors associated with Pi alterations, and the effect of phosphate repletion on the normalization of Pi levels, and its associations with clinical outcomes. METHODS: This multicentre, prospective, non-interventional cohort study will include at least 1000 consecutive adult ICU patients (≥18 years) as part B of the GUTPHOS study. Sites are eligible if an anticipated minimal inclusion of 50 eligible patients during eight weeks from January 2024 until June 2024 and daily phosphate measurements during the first seven days of ICU stay are expected. All consecutive adult patients admitted to a participating ICU during the recruitment period, lasting up to eight weeks, or up to 120 patients if enrollment reaches that limit earlier, will be included. Study parameters include study site characteristics, patient demographics, daily assessment of Pi levels, Pi-related treatment, feeding details, renal replacement therapy details, the incidence of refeeding-associated hypophosphatemia and administered medication (during the first seven calendar days of ICU stay). There will be a follow-up period of a maximum of 90 days to document 28- and 90-day all-cause mortality as the primary outcome. Multiple logistic regression will be used to assess independent associations with mortality in addition to Receiver Operating Characteristics curves to identify cut-off Pi values associated with mortality and overcorrection. Linear mixed models will be conducted to assess Pi treatment effects. Subgroup analyses will be performed based on Pi abnormalities observed during ICU admission, categorized as normo-, hypo-, hyper-, or mixed, along with its severity (mild, moderate, or severe). DISCUSSION: The GUTPHOS study will be the first multicentre, prospective observational cohort study to investigate the prevalence, management practices, and consequent outcomes associated with Pi abnormalities during the first week of ICU admission. Its results may bridge the current evidence gap in repletion protocols while establishing the groundwork for a subsequent randomized controlled trial.

Statistical analysis plan for the replacing protein via enteral nutrition in a stepwise approach in critically ill patients (REPLENISH) randomized clinical trial.

BACKGROUND: The optimal amount and timing of protein intake in critically ill patients are unknown. REPLENISH (Replacing Protein via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients) trial evaluates whether supplemental enteral protein added to standard enteral nutrition to achieve a high amount of enteral protein given from ICU day five until ICU discharge or ICU day 90 as compared to no supplemental enteral protein to achieve a moderate amount of enteral protein would reduce all-cause 90-day mortality in adult critically ill mechanically ventilated patients. METHODS: In this multicenter randomized trial, critically ill patients will be randomized to receive supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition to achieve a high amount of enteral protein (range of 2-2.4 g/kg/day) or no supplemental enteral protein to achieve a moderate amount of enteral protein (0.8-1.2 g/kg/day). The primary outcome is 90-day all-cause mortality; other outcomes include functional and health-related quality-of-life assessments at 90 days. The study sample size of 2502 patients will have 80% power to detect a 5% absolute risk reduction in 90-day mortality from 30 to 25%. Consistent with international guidelines, this statistical analysis plan specifies the methods for evaluating primary and secondary outcomes and subgroups. Applying this statistical analysis plan to the REPLENISH trial will facilitate unbiased analyses of clinical data. CONCLUSION: Ethics approval was obtained from the institutional review board, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia (RC19/414/R). Approvals were also obtained from the institutional review boards of each participating institution. Our findings will be disseminated in an international peer-reviewed journal and presented at relevant conferences and meetings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04475666 . Registered on July 17, 2020.

Risk factors for intra-abdominal hypertension and abdominal compartment syndrome among adult intensive care unit patients: a systematic review and meta-analysis.

INTRODUCTION: Although intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are associated with substantial morbidity and mortality among critically ill adults, it remains unknown if prevention or treatment of these conditions improves patient outcomes. We sought to identify evidence-based risk factors for IAH and ACS in order to guide identification of the source population for future IAH/ACS treatment trials and to stratify patients into risk groups based on prognosis. METHODS: We searched electronic bibliographic databases (MEDLINE, EMBASE, PubMed, and the Cochrane Database from 1950 until January 21, 2013) and reference lists of included articles for observational studies reporting risk factors for IAH or ACS among adult ICU patients. Identified risk factors were summarized using formal narrative synthesis techniques alongside a random effects meta-analysis. RESULTS: Among 1,224 citations identified, 14 studies enrolling 2,500 patients were included. The 38 identified risk factors for IAH and 24 for ACS could be clustered into three themes and eight subthemes. Large volume crystalloid resuscitation, the respiratory status of the patient, and shock/hypotension were common risk factors for IAH and ACS that transcended across presenting patient populations. Risk factors with pooled evidence supporting an increased risk for IAH among mixed ICU patients included obesity (four studies; odds ratio (OR) 5.10; 95% confidence interval (CI), 1.92 to 13.58), sepsis (two studies; OR 2.38; 95% CI, 1.34 to 4.23), abdominal surgery (four studies; OR 1.93; 95% CI, 1.30 to 2.85), ileus (two studies; OR 2.05; 95% CI, 1.40 to 2.98), and large volume fluid resuscitation (two studies; OR 2.17; 95% CI, 1.30 to 3.63). Among trauma and surgical patients, large volume crystalloid resuscitation and markers of shock/hypotension and metabolic derangement/organ failure were risk factors for IAH and ACS while increased disease severity scores and elevated creatinine were risk factors for ACS in severe acute pancreatitis patients. CONCLUSIONS: Although several IAH/ACS risk factors transcend across presenting patient diagnoses, some appear specific to the population under study. As our findings were somewhat limited by included study methodology, the risk factors reported in this study should be considered candidate risk factors until confirmed by a large prospective multi-centre observational study.

Acute abdominal pain at referral emergency departments: an analysis of performance of three time-dependent quality indicators.

BACKGROUND: Abdominal pain is one of the most frequent causes for emergency department (ED) visits. The quality of care and outcomes are determined by time-dependent interventions with barriers to implementation at crowded EDs. OBJECTIVES: The study aimed to analyze three prominent quality indicators (QI) including pain assessment (QI1), analgesia in patients reporting severe pain (QI2), and ED length of stay (LOS) (QI3) in adult patients requiring immediate or urgent care due to acute abdominal pain. We aimed to characterize current practice regarding pain management, and we hypothesized that extended ED LOS (≥ 360 min) is associated with poor outcomes in this cohort of ED referrals. METHODS: This is a retrospective cohort study enrolling all patients with acute abdominal pain as the main cause of ED presentation, triage category red, orange, or yellow, and age ≥ 30 years during two months period. Univariate and multivariable analyses were deployed to determine independent risk factors for QIs performance. For QI1 and QI2, compliance with the QIs were analyzed, while 30-day mortality was set as primary outcome for QI3. RESULTS: Overall, 965 patients were analyzed including 501 (52%) males with a mean age of 61.8 years. Seventeen percent (167/965) of the patients had immediate or very urgent triage category. Age ≥ 65 years, and red and orange triage categories were risk factors for non-compliance with pain assessment. Seventy four per cent of patients with severe pain (numeric rating scale ≥ 7) received analgesia during the ED visit, in median within 64 min (IQR 35-105 min). Age ≥ 65 years and need for surgical consultation were risk factors for prolonged ED stay. After adjustment to age, gender and triage category, ED LOS ≥ 360 min proved to be independent risk factor for 30-day mortality (HR 1.89, 95% CI 1.71-3.40, p = 0.034). CONCLUSION: Our investigation identified that non-compliance with pain assessment, analgesia and ED length of stay among patients presenting with abdominal pain to ED results in poor quality of care and detrimental outcomes. Our data support enhanced quality-assessment initiatives for this subset of ED patients.