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author:("tarkops, Joel")
1.  Moderate Intra-Abdominal Hypertension Leads to Anaerobic Metabolism in the Rectus Abdominis Muscle Tissue of Critically Ill Patients: A Prospective Observational Study 
BioMed Research International  2014;2014:857492.
Purpose. We hypothesize that intra-abdominal hypertension (IAH) is associated with the presence of anaerobic metabolism in the abdominal rectus muscle (RAM) tissue of critically ill patients. Methods. We included 10 adult, critically ill patients with intra-abdominal pressure (IAP) above 12 mmHg. Microdialysis catheters (CMA 60) were inserted into the RAM tissue. The samples were collected up to 72 hours after enrollment. Results. The patients' median (IQR) APACHE II at inclusion was 29 (21–37); 7 patients were in shock. IAP was 14.5 (12.5–17.8) mmHg at baseline and decreased significantly over time, concomitantly with arterial lactate and vasopressors requirements. The tissue lactate-to-pyruvate (L/P) ratio was 49 (36–54) at the beginning of the study and decreased significantly throughout the study. Additionally, the tissue lactate, lactate-to-glucose (L/G) ratio, and glutamate concentrations changed significantly during the study. The correlation analysis showed that lower levels of pyruvate and glycerol were associated with higher MAP and abdominal perfusion pressures (APP) and that higher levels of glutamate were correlated to elevated IAP. Conclusions. Moderate IAH leads to RAM tissue anaerobic metabolism suggestive for hypoperfusion in critically ill patients. Correlation analysis supports the concept of using APP as the primary endpoint of resuscitation in addition to MAP and IAP.
PMCID: PMC3973001  PMID: 24745026
2.  Risk factors for intra-abdominal hypertension and abdominal compartment syndrome among adult intensive care unit patients: a systematic review and meta-analysis 
Critical Care  2013;17(5):R249.
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.
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.
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.
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.
PMCID: PMC4057241  PMID: 24144138
3.  Growth Factors Serum Levels in Coronary Artery Disease Patients Scheduled for Bypass Surgery: Perioperative Dynamics and Comparisons with Healthy Volunteers 
BioMed Research International  2013;2013:985404.
Background. Vascular endothelial growth factors are important mediators for neovascularization of chronically ischemic adult heart, but their elevated values have also been connected with acute ischemia. Coronary artery bypass grafting (CABG) is associated with activation of inflammatory processes. We aimed to clarify whether the latter is also accompanied with acute changes in concentrations of vascular growth factors. Methods. Concentrations of growth factors VEGF and EGF, monocyte chemoattractant protein-1 (MCP-1), and a set of cytokines of 39 patients with stable coronary artery disease (CAD) were evaluated before and after CABG. Preoperative values were compared with data of healthy volunteers. Results. In comparison with CAD patients, healthy controls had significantly higher values of VEGF (15.5 (10.05–35.3) and 119.4 (55.7–136.9) pg/mL, resp.), EGF (1.70 (1.14–3.18) and 37.3 (27.1–51.9) pg/mL, resp.), and MCP-1 (111.6 (81.75–171.9) and 156.9 (134.7–241.3) pg/mL, resp.). MCP-1, but not others, demonstrated a significant rise throughout the postoperative period. Proinflammatory interleukin-6 was significantly higher and anti-inflammatory IL-4 and IL-10 lower in patients with CAD. Conclusions. Patients with stable CAD have lower serum levels of growth factors than healthy volunteers. MCP-1, but not VEGF and EGF, becomes elevated immediately after CABG. Inflammatory status of CAD patients was drifted towards proinflammatory state.
PMCID: PMC3745908  PMID: 23984427
4.  Gastrointestinal symptoms during the first week of intensive care are associated with poor outcome: a prospective multicentre study 
Intensive Care Medicine  2013;39(5):899-909.
The study aimed to develop a gastrointestinal (GI) dysfunction score predicting 28-day mortality for adult patients needing mechanical ventilation (MV).
377 adult patients from 40 ICUs with expected duration of MV for at least 6 h were prospectively studied. Predefined GI symptoms, intra-abdominal pressures (IAP), feeding details, organ dysfunction and treatment were documented on days 1, 2, 4 and 7.
The number of simultaneous GI symptoms was higher in nonsurvivors on each day. Absent bowel sounds and GI bleeding were the symptoms most significantly associated with mortality. None of the GI symptoms alone was an independent predictor of mortality, but gastrointestinal failure (GIF)—defined as three or more GI symptoms—on day 1 in ICU was independently associated with a threefold increased risk of mortality. During the first week in ICU, GIF occurred in 24 patients (6.4 %) and was associated with higher 28-day mortality (62.5 vs. 28.9 %, P = 0.001). Adding the created subscore for GI dysfunction (based on the number of GI symptoms) to SOFA score did not improve mortality prediction (day 1 AUROC 0.706 [95 % CI 0.647–0.766] versus 0.703 [95 % CI 0.643–0.762] in SOFA score alone).
An increasing number of GI symptoms independently predicts 28 day mortality with moderate accuracy. However, it was not possible to develop a GI dysfunction score, improving the performance of the SOFA score either due to data set limitations, definition problems, or possibly indicating that GI dysfunction is often secondary and not the primary cause of other organ failure.
PMCID: PMC3625421  PMID: 23370829
Gastrointestinal symptoms; Gastrointestinal dysfunction; Intensive care; Outcome
5.  Effects of 60 minutes of hyperoxia followed by normoxia before coronary artery bypass grafting on the inflammatory response profile and myocardial injury 
Ischemic preconditioning induces tolerance against ischemia-reperfusion injury prior a sustained ischemic insult. In experimental studies, exposure to hyperoxia for a limited time before ischemia induces a low-grade systemic oxidative stress and evokes an (ischemic) preconditioning-like effect of the myocardium. We hypothesised that pre-treatment by hyperoxia favours enchanced myocardial protection described by decreased release of cTn T in the 1st postoperative morning and reduces the release of inflammatory cytokines.
Forty patients with stable coronary artery disease underwent coronary artery bypass grafting with cardiopulmonary bypass. They were ventilated with 40 or >96% oxygen for 60 minutes followed by by 33 (18–59) min normoxia before cardioplegia.
In the 1st postoperative morning concentrations of cTnT did not differ between groups ((0.44 (0.26-0.55) ng/mL in control and 0.45 (0.37-0.71) ng/mL in hyperoxia group). Sixty minutes after declamping the aorta, ratios of IL-10/IL-6 (0.73 in controls and 1.47 in hyperoxia, p = 0.03) and IL-10/TNF-α (2.91 and 8.81, resp., p = 0.015) were significantly drifted towards anti-inflammatory, whereas interleukins 6, 8and TNF-α and interferon-γ showed marked postoperative rise, but no intergroup differences were found.
Pre-treatment by 60 minutes of hyperoxia did not reduce postoperative leak of cTn T in patients undergoing coronary artery bypass surgery. In the hyperoxia group higher release of anti-inflammatory IL-10 caused drifting of IL-10/IL-6 and IL-10/TNF-α towards anti-inflammatory.
PMCID: PMC3460785  PMID: 22978419
Coronary artery bypass grafting; Preconditioning; Hyperoxia; Troponin T; Cytokine; Interleukin; Tumor necrosis factor alfa; Interferon gamma
6.  Should we measure intra-abdominal pressures in every intensive care patient? 
Annals of Intensive Care  2012;2(Suppl 1):S9.
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.
PMCID: PMC3390289  PMID: 22873425
intra-abdominal pressure; intra-abdominal hypertension; abdominal compartment syndrome; patient monitoring; intensive care; epidemiology.
7.  Moderate intra-abdominal hypertension is associated with an increased lactate-pyruvate ratio in the rectus abdominis muscle tissue: a pilot study during laparoscopic surgery 
Annals of Intensive Care  2012;2(Suppl 1):S14.
The development of intra-abdominal hypertension [IAH] in critically ill patients admitted to the ICU is an independent predictor of mortality. In an attempt to find an early, clinically relevant metabolic signal of modest IAH, we investigated abdominal wall metabolite concentrations in a small group of patients undergoing laparoscopic surgery. We hypothesized that elevated intra-abdominal pressure [IAP] due to pneumoperitoneum leads to an increased lactate/pyruvate [L/P] ratio in the rectus abdominis muscle [RAM], indicating anaerobic metabolism.
Six patients scheduled for elective laparoscopic gastric fundoplication were studied. Two hours before surgery, a microdialysis catheter (CMA 60, CMA Small Systems AB, Solna, Sweden) was inserted into the RAM under local anaesthesia. Catheter placement was confirmed by ultrasound. The microdialysis perfusion rate was set at 0.3 μL/min. Dialysate was collected hourly prior to pneumoperitoneum, during pneumoperitoneum, and for 2 h after pneumoperitoneum resolution. IAP was maintained at 12 to 13 mmHg during the surgery. The glucose, glycerol, pyruvate and lactate contents of the dialysate were measured.
The median (interquartile range) L/P ratio was 10.3 (7.1 to 15.5) mmol/L at baseline. One hour of pneumoperitoneum increased the L/P ratio to 16.0 (13.6 to 35.3) mmol/L (p = 0.03). The median pneumoperitoneum duration was 86 (77 to 111) min. The L/P ratio at 2 h post-pneumoperitoneum was not different from that at baseline (p = 1.0). No changes in glycerol or glucose levels were observed.
IAH of 12 to 13 mmHg, even for a relatively short duration, is associated with metabolic changes in the abdominal wall muscle tissue of patients undergoing laparoscopic surgery. We suggest that tissue hypoperfusion occurs even during a modest increase in IAP, and intramuscular metabolic monitoring could therefore serve as an early warning sign of deteriorating tissue perfusion.
PMCID: PMC3390303  PMID: 22873415
microdialysis; intra-abdominal pressure; intra-abdominal hypertension; lactate-to-pyruvate ratio; muscle ischemia; early clinical sign
8.  Gastrointestinal function in intensive care patients: terminology, definitions and management. Recommendations of the ESICM Working Group on Abdominal Problems 
Intensive Care Medicine  2012;38(3):384-394.
Acute gastrointestinal (GI) dysfunction and failure have been increasingly recognized in critically ill patients. The variety of definitions proposed in the past has led to confusion and difficulty in comparing one study to another. An international working group convened to standardize the definitions for acute GI failure and GI symptoms and to review the therapeutic options.
The Working Group on Abdominal Problems (WGAP) of the European Society of Intensive Care Medicine (ESICM) developed the definitions for GI dysfunction in intensive care patients on the basis of the available evidence and current understanding of the pathophysiology.
Definitions for acute gastrointestinal injury (AGI) with its four grades of severity, as well as for feeding intolerance syndrome and GI symptoms (e.g. vomiting, diarrhoea, paralysis, high gastric residual volumes) are proposed. AGI is a malfunctioning of the GI tract in intensive care patients due to their acute illness. AGI grade I = increased risk of developing GI dysfunction or failure (a self-limiting condition); AGI grade II = GI dysfunction (a condition that requires interventions); AGI grade III = GI failure (GI function cannot be restored with interventions); AGI grade IV = dramatically manifesting GI failure (a condition that is immediately life-threatening). Current evidence and expert opinions regarding treatment of acute GI dysfunction are provided.
State-of-the-art definitions for GI dysfunction with gradation as well as management recommendations are proposed on the basis of current medical evidence and expert opinion. The WGAP recommends using these definitions for clinical and research purposes.
Electronic supplementary material
The online version of this article (doi:10.1007/s00134-011-2459-y) contains supplementary material, which is available to authorized users.
PMCID: PMC3286505  PMID: 22310869
Gastrointestinal function; Failure; Symptoms; Feeding intolerance; Intensive care; Definitions; Classification
9.  Intra-Abdominal Hypertension and Gastrointestinal Symptoms in Mechanically Ventilated Patients 
Background. We aimed to describe the incidence of intra-abdominal hypertension (IAH) and gastrointestinal (GI) symptoms and related outcome in mechanically ventilated (MV) patients. Methods. Intra-abdominal pressure (IAP) and gastric residual volumes were measured at least twice daily. IAH was defined as a mean daily value of IAP ≥ 12 mmHg. Results. 398 patients were monitored for all together 2987 days. GI symptom(s) occurred in 80.2% patients. 152 (38.2%) patients developed IAH. Majority (93.4%) of patients with IAH had GI symptoms. The more severe IAH was associated with the higher number of concomitant GI symptoms (P < .001). 142 (35.7%) patients developed both IAH and at least one GI symptom at any time in ICU, and in 77 patients they occurred simultaneously on the same day. This subgroup had the highest ICU mortality (21.8%). In contrast, the small group of patients presenting only IAH, but not GI symptoms (10 patients), had no lethal outcome. Three patients (4.4%) died without showing either IAH or GI symptoms. Conclusions. GI symptoms and IAH often, but not always, occur together. The patients having IAH solely without developing GI symptoms have rather good outcome.
PMCID: PMC3087429  PMID: 21547094
11.  Gastrointestinal Failure score in critically ill patients: a prospective observational study 
Critical Care  2008;12(4):R90.
There are no universally accepted diagnostic criteria for gastrointestinal failure in critically ill patients. In the present study we tested whether the occurrence of food intolerance (FI) and intra-abdominal hypertension (IAH), combined in a 5-grade scoring system for assessment of gastrointestinal function (the Gastrointestinal Failure [GIF] score), predicts mortality. The prognostic value of the GIF score alone and in combination with the Sequential Organ Failure Assessment (SOFA) score is evaluated, and the incidence and outcome of gastrointestinal failure is described relative to the GIF score.
A total of 264 subsequently hospitalized patients, who were mechanically ventilated on admission and stayed in the intensive care unit (ICU) for longer than 24 hours, were prospectively studied. GIF score was documented daily as follows: 0 = normal gastrointestinal function; 1 = enteral feeding with under 50% of calculated needs or no feeding 3 days after abdominal surgery; 2 = FI or IAH; 3 = FI and IAH; and 4 = abdominal compartment syndrome (ACS). Admission parameters and mean GIF and SOFA scores for the first 3 days were used to predict ICU outcome.
FI developed in 58.3%, IAH in 27.3%, and both together in 22.7% of patients. The mean GIF score for the first 3 days in the ICU was identified as an independent risk factor for mortality (odds ratio = 3.02, 95% confidence interval = 1.63 to 5.59; P < 0.001). The GIF score integrated into the SOFA score allowed better prediction of ICU mortality than did the SOFA score alone, and was an independent predictor of mortality (odds ratio = 1.49, 95% confidence interval = 1.28 to 1.74; P < 0.001). The development of gastrointestinal failure (FI plus IAH) was associated with significantly higher ICU and 90-day mortality.
The GIF score is useful for classifying information on the gastrointestinal system. The mean GIF score during the first 3 days in the ICU had high prognostic value for ICU mortality. Development of gastrointestinal failure is associated with significantly impaired outcome.
PMCID: PMC2575570  PMID: 18625051
12.  Gastrointestinal failure in intensive care: a retrospective clinical study in three different intensive care units in Germany and Estonia 
BMC Gastroenterology  2006;6:19.
While gastrointestinal problems are common in ICU patients with multiple organ failure, gastrointestinal failure has not been given the consideration other organ systems receive. The aim of this study was to evaluate the incidence of gastrointestinal failure (GIF), to identify its risk factors, and to determine its association with ICU mortality.
A retrospective analysis of adult patients (n = 2588) admitted to three different ICUs (two ICUs at the university hospital Charité-Universitätsmedizin Berlin, Germany and one at Tartu University Clinics, Estonia) during the year 2002 was performed.
Data recorded in a computerized database were used in Berlin. In Tartu, the data documented in the patients' charts was retrospectively transferred into a similar database. GIF was defined as documented gastrointestinal problems (food intolerance, gastrointestinal haemorrhage, and/or ileus) in the patient data at any period of their ICU stay. ICU mortality, length of stay, and duration of mechanical ventilation were assessed as outcome parameters.
GIF was identified in 252 patients (9.7% of all patients). Only 20% of GIF patients were identifiable at admission. GIF was related to significantly higher mortality (43.7% vs. 5.3% in patients without GIF), as well as prolonged length of ICU stay (10 vs. 2 days) and mechanical ventilation (8 vs. 1 day), p < 0.001, respectively. Patients' profile (emergency surgical or medical), APACHE II and SOFA scores and the use of catecholamines at admission were identified as independent risk factors for the development of GIF. Development of GIF during ICU stay was an independent predictor for death.
Gastrointestinal failure represents a relevant clinical problem accompanied by an increased mortality, longer ICU stay and mechanical ventilation.
PMCID: PMC1513588  PMID: 16792799

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