The intensivist's assessment of gastrointestinal function: A pilot study.

Gastrointestinal dysfunction/failure (GDF) is a common cause of concern in critically ill patients. Although the gut plays an important role in the genesis of organ failure, its exclusion from organ severity scoring systems has made it challenging for intensivists to score it sufficiently at the bedside. We aimed to survey intensive care specialists about their perceptions, attitudes, and approaches towards the assessment of the gut in Australia and New Zealand intensive care units (ICUs). An electronic (online) questionnaire was used to survey intensive care specialists from the Australia and New Zealand Intensive Care Society (ANZICS). The survey comprised 10 questions focused on four key areas: (i) the extent of the problem with GDF in ICUs, (ii) the use and reliability of the current gut scoring tools, (iii) personal approaches and practices associated with GDF assessment, and (4) potential value of a novel GDF scoring system and its incorporation into an organ severity score. Our results showed that GDF was a significant concern amongst ICUs in Australia and New Zealand intensivists (84%; 66/79), with a small number of participants (14%; 3/79) using a gut scoring tool in their ICUs. Despite this, we have no established objective scoring tool for its assessment. The survey highlighted the need for developing a novel scoring tool to assess the gut was considered important amongst majority of the intensivists (92%; 72/78), which would prove useful in clinical practice and potentially lead to incorporation into an organ severity score in the future.

Impact of Intravenous Fluids and Enteral Nutrition on the Severity of Gastrointestinal Dysfunction: A Systematic Review and Meta-analysis.

INTRODUCTION: Gastrointestinal dysfunction (GDF) is one of the primary causes of morbidity and mortality in critically ill patients. Intensive care interventions, such as intravenous fluids and enteral feeding, can exacerbate GDF. There exists a paucity of high-quality literature on the interaction between these two modalities (intravenous fluids and enteral feeding) as a combined therapy on its impact on GDF. AIM: To review the impact of intravenous fluids and enteral nutrition individually on determinants of gut function and implications in clinical practice. METHODS: Randomized controlled trials on intravenous fluids and enteral feeding on GDF were identified by a comprehensive database search of MEDLINE and EMBASE. Extraction of data was conducted for study characteristics, provision of fluids or feeding in both groups and quality of studies was assessed using the Cochrane criteria. A random-effects model was applied to estimate the impact of these interventions across the spectrum of GDF severity. RESULTS: Restricted/ goal-directed intravenous fluid therapy is likely to reduce 'mild' GDF such as vomiting (p = 0.03) compared to a standard/ liberal intravenous fluid regime. Enterally fed patients experienced increased episodes of vomiting (p = <0.01) but were less likely to develop an anastomotic leak (p = 0.03) and peritonitis (p = 0.03) compared to parenterally fed patients. Vomiting (p = <0.01) and anastomotic leak (p = 0.04) were significantly lower in the early enteral feeding group. CONCLUSIONS: There is less emphasis on the combined approach of intravenous fluid resuscitation and enteral feeding in critically ill patients. Conservative fluid resuscitation and aggressive enteral feeding are presumably key factors contributing to severe life-threatening GDF. Future trials should evaluate the impact of cross-interaction between conservative and aggressive modes of these two interventions on the severity of GDF.

Gastrointestinal Dysfunction in Critical Illness: A Review of Scoring Tools.

Gastrointestinal dysfunction/failure (GDF) is a common feature of critical illness. There is no consensus on the best way to measure severity of GDF. The aim of this systematic review was to evaluate and compare all gastrointestinal dysfunction scoring tools (GDSTs) to determine aspects that might be useful to construct a new gut scoring tool for intensive care patients. A comprehensive database search of MEDLINE and EMBASE on GDSTs in acute, surgical, and critically ill patients was conducted. Extraction of data was conducted for study characteristics, GDST domains, feasibility of the scoring process, clinical outcomes, and quality of life attributes; independent authors conducted the search, applied the selection criteria, and extracted the data. Methodological quality of studies was assessed. A GDST matrix was created using 14 scoring tools and was evaluated for validity. The 14 GDSTs identified were used in different clinical settings, including critical illness, acute intestinal failure, gastrointestinal disorders, and postoperative patients. There was marked variation between these GDSTs. There is a lack of emphasis in the use of objective laboratory parameters and gut-specific biomarkers to measure GDF in majority of the studies. The overall quality of evidence was poor, and most tools lacked formal validation. This review has highlighted the lack of an agreed and validated approach to scoring GDF in critical illness. The identified aspects of GDF relevant to critical illness should now be incorporated in a new scoring tool and prospectively tested in intensive care patients.

Effect of Intravenous Fluids and Analgesia on Dysmotility in Patients With Acute Pancreatitis: A Prospective Cohort Study.

OBJECTIVES: Analgesia and intravenous fluid resuscitation are cornerstones of initial patient management in acute pancreatitis (AP). The aim was to investigate the effect of intravenous fluids and analgesia on gastrointestinal motility in the early course of AP. METHODS: Gastrointestinal dysmotility was assessed using the Gastroparesis Cardinal Symptom Index (GCSI). One-way analysis of variance and analysis of covariance were conducted, adjusting for age, sex, body mass index, severity of AP, preexisting diabetes mellitus, and time from first symptom onset to hospital admission. RESULTS: A total of 108 patients with AP were prospectively enrolled. Opioid analgesia, when compared with nonopioid analgesia, was significantly associated with increase in total GCSI score in both unadjusted and adjusted analyses. There was no significant difference between aggressive and nonaggressive fluid resuscitation in both unadjusted and adjusted analyses. A combination of opioids and any intravenous fluids was associated with a significantly increased total GCSI score compared with opioids and no intravenous fluids in both unadjusted and adjusted analyses. Duration of symptoms was the confounder that significantly affected 6 of 9 studied associations. CONCLUSIONS: Intravenous fluids and analgesia significantly affect motility independent of severity and other covariates. Guidelines on prudent use of opioids and fluids in AP need to be developed, particularly taking into account duration of symptoms from onset to hospitalization.

Glucose Variability Measures as Predictors of Oral Feeding Intolerance in Acute Pancreatitis: A Prospective Pilot Study.

BACKGROUND: Oral feeding intolerance (OFI) is a common complication in patients with acute pancreatitis (AP). Variations in blood glucose are associated with impaired gastrointestinal function but, to date, measures of glucose variability have not been investigated to predict OFI in patients with AP. AIM: To investigate the usefulness of several glucose variability measures in predicting the occurrence of OFI early in the course of AP. METHODS: In this prospective cohort study, six measures of glucose variability were calculated prior to the occurrence of OFI. Multivariate binary logistic regression analyses were conducted, and the diagnostic performance and accuracy of glucose variability measures were assessed. RESULTS: Of the 95 prospectively enrolled patients, 21 (22%) developed OFI. After adjusting for confounders, admission blood glucose concentration and mean blood glucose concentration were significantly associated with OFI [odds ratio 1.49 (95% confidence interval 1.01-2.20) and odds ratio 1.67 (95% confidence interval 1.07-2.61), respectively]. Both admission blood glucose and mean blood glucose had an area under the curve of 0.83 and positive likelihood ratios of 6.45 and 10.19, respectively. Blood glucose concentration before refeeding, standard deviation of blood glucose concentration, coefficient of variation, and mean amplitude of glycemic excursions were not significantly associated with OFI. CONCLUSION: In-hospital blood glucose concentrations are associated with subsequent development of OFI in patients with AP. In particular, admission blood glucose and mean blood glucose could be useful predictors of OFI in this setting.

New-Onset Diabetes After Acute and Critical Illness: A Systematic Review.

Hyperglycemia is commonly observed during acute and critical illness. Recent studies have investigated the risk of developing diabetes after acute and critical illness, but the relationship between degree of in-hospital hyperglycemia and new-onset diabetes has not been investigated. This study examines the evidence for the relationship between in-hospital hyperglycemia and prevalence of new-onset diabetes after acute and critical illness. A literature search was performed of the MEDLINE, EMBASE, and Scopus databases for relevant studies published from January 1, 2000, through August 4, 2016. Patients with no history of diabetes before hospital discharge were included in the systematic review. In-hospital glucose concentration was classified as normoglycemia, mild hyperglycemia, or severe hyperglycemia for the meta-analysis. Twenty-three studies were included in the systematic review, and 18 of these (111,078 patients) met the eligibility criteria for the meta-analysis. The prevalence of new-onset diabetes was significantly related to in-hospital glucose concentration and was 4% (95% CI, 2%-7%), 12% (95% CI, 9%-15%), and 28% (95% CI, 18%-39%) for patients with normoglycemia, mild hyperglycemia, and severe hyperglycemia, respectively. The prevalence of new-onset diabetes was not influenced by disease setting, follow-up duration, or study design. In summary, this study found stepwise growth in the prevalence of new-onset diabetes with increasing in-hospital glucose concentration. Patients with severe hyperglycemia are at the highest risk, with 28% developing diabetes after hospital discharge.

Nomogram for predicting oral feeding intolerance in patients with acute pancreatitis.

OBJECTIVES: Oral feeding intolerance (OFI) is a common complication of acute pancreatitis that leads to prolonged hospitalization, increased use of hospital resources, and impaired quality of life. However, there are no clinically useful predictors of OFI. The aims of this study were to determine whether gastrointestinal dysmotility is associated with the development of OFI, and whether the gastroparesis cardinal symptom index (GCSI) can be used as a predictive tool in a clinical setting. METHODS: This was a prospective cohort study. The primary outcome was the development of OFI. Daily GCSI total score and subscores (nausea/vomiting, early satiety, and bloating) were recorded. Univariate and multivariate binary logistic regression analyses were conducted, adjusting for age, etiology of pancreatitis, severity, diabetes status, and time from symptom onset to hospital admission. RESULTS: The study included 217 consecutive adult patients with acute pancreatitis. Multivariate analyses showed significant associations between OFI occurrence and the total GCSI score on day 2 of hospital admission (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.02-2.00), the highest total GCSI score (OR, 1.38; 95% CI, 1.03-1.86), the day 2 nausea/vomiting subscore (OR, 1.40; 95% CI, 1.04-1.89), the day 2 bloating subscore (OR, 1.25; 95% CI, 1.01-1.54), and the highest bloating subscore (OR, 1.32; 95% CI, 1.08-1.63). CONCLUSIONS: Gastrointestinal dysmotility is associated with the development of OFI and the GCSI has potential as a clinically useful predictive tool in the setting of acute pancreatitis. The developed nomogram holds promise but needs to be validated externally.

Lipid metabolism in patients with chronic hyperglycemia after an episode of acute pancreatitis.

BACKGROUND: The importance of dyslipidemia is well recognized in the context of both risk factor for acute pancreatitis and prognostic factor for its in-hospital outcomes. With a growing appreciation of post-pancreatitis diabetes mellitus, there is a need to catalogue changes in lipid metabolism after hospitalization due to an acute pancreatitis attack and their associations with glucose metabolism. OBJECTIVE: To investigate lipid metabolism in patients with impaired glucose homeostasis following acute pancreatitis. METHODS: There were two study groups: newly diagnosed chronic hyperglycemia or normoglycemia after acute pancreatitis. During the fasting state, venous blood samples were collected to analyse markers of lipid metabolism (triglycerides, glycerol, low density lipoprotein, high density lipoprotein, total cholesterol, free fatty acids, and apolipoprotein-B) and glucose metabolism (HbA1c, insulin, index of adipose tissue insulin resistance (Adipo-IR), and HOMA-IR). Binary logistic and linear regression analyses were conducted, and potential confounders were adjusted for in multivariate analyses. RESULTS: The study included 64 patients with normoglycemia and 19 - with chronic hyperglycemia. Glycerol was significantly associated with the development of chronic hyperglycemia in both unadjusted (p=0.02) and adjusted (p=0.006) models. Triglycerides were significantly associated with the development of chronic hyperglycemia in adjusted (p=0.019) model. Other markers of lipid metabolism did not differ significantly between the two groups. None of the markers of lipid metabolism was significantly associated with Adipo-IR or HOMA-IR. CONCLUSION: Overall, patients with chronic hyperglycemia after acute pancreatitis appear to have a lipid profile indicative of an up-regulation of lipolysis, which is not significantly affected by either general or adipose tissue-specific insulin resistance.

The Role of Gut-brain Axis in Regulating Glucose Metabolism After Acute Pancreatitis.

OBJECTIVES: Diabetes has become an epidemic in developed and developing countries alike, with an increased demand for new efficacious treatments. A large body of pre-clinical evidence suggests that the gut-brain axis may be exploited as a potential therapeutic target for defective glucose homeostasis. This clinical study aimed to investigate a comprehensive panel of glucoregulatory peptides, released by both the gut and brain, in individuals after acute pancreatitis. METHODS: Fasting levels of glucagon-like peptide-1 (GLP-1), glicentin, oxyntomodulin, peptide YY, ghrelin, cholecystokinin, vasoactive intestinal peptide (VIP), and secretin were studied. Modified Poisson and multivariable linear regression analyses were conducted. Pre-determined concentration ranges were used to categorize each peptide into quartiles. RESULTS: A total of 83 individuals were included, of who 30 (36%) developed abnormal glucose metabolism (AGM) after acute pancreatitis. In individuals with AGM, the highest quartile of oxyntomodulin differed most significantly from the lowest quartile with a prevalence ratio (PR; 95% confidence interval) of 0.50 (0.21, 1.20; P=0.005); of glicentin with a PR of 0.26 (0.13, 0.54; P<0.001); and of VIP with a PR of 0.34 (0.13, 0.89; P=0.043). Peptide YY, GLP-1, cholecystokinin, ghrelin, and secretin were not significantly associated with AGM. CONCLUSIONS: Fasting circulating oxyntomodulin, glicentin, and VIP levels are significantly decreased in patients with defective glucose homeostasis after acute pancreatitis. Oxyntomodulin appears to be a promising therapeutic target for future clinical studies on diabetes associated with diseases of the exocrine pancreas.

Incidence and predictors of oral feeding intolerance in acute pancreatitis: A systematic review, meta-analysis, and meta-regression.

BACKGROUND: Tolerance of oral food is an important criterion for hospital discharge in patients with acute pancreatitis. Patients who develop oral feeding intolerance have prolonged hospitalisation, use additional healthcare resources, and have impaired quality of life. This study aimed to quantify the incidence of oral feeding intolerance, the effect of confounders, and determine the best predictors of oral feeding intolerance. METHODS: Clinical studies indexed in three electronic databases (EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials) were reviewed. Incidence and predictor data were meta-analysed and possible confounders were investigated by meta-regression analysis. RESULTS: A total of 22 studies with 2024 patients met the inclusion criteria, 17 of which (with 1550 patients) were suitable for meta-analysis. The incidence of oral feeding intolerance was 16.3%, and was not affected by WHO region, age, sex, or aetiology of acute pancreatitis. Nine of the 22 studies investigated a total of 62 different predictors of oral feeding intolerance. Serum lipase level prior to refeeding, pleural effusions, (peri)pancreatic collections, Ranson score, and Balthazar score were found to be statistically significant in meta-analyses. CONCLUSIONS: Oral feeding intolerance affects approximately 1 in 6 patients with acute pancreatitis. Serum lipase levels of more than 2.5 times the upper limit of normal prior to refeeding is a potentially useful threshold to identify patients at high risk of developing oral feeding intolerance.

Interleukin-6 is associated with chronic hyperglycemia and insulin resistance in patients after acute pancreatitis.

BACKGROUND: Diabetes is a pervasive disease, with a mounting prevalence and burden on health care systems. Under this collective term of diabetes falls diabetes after diseases of the exocrine pancreas, a condition which was previously under-recognised and often mislabeled as type 2 diabetes mellitus and is now increasingly acknowledged as a stand-alone entity. However, there is a paucity of clinical studies investigating the underlying pathophysiology of diabetes after acute pancreatitis, the most frequent disease of the pancreas. This study aimed to investigate the role of adipocytokines in glucose metabolism after acute pancreatitis. METHODS: This was a cross-sectional follow-up study of a patient cohort diagnosed with acute pancreatitis. Fasting venous blood samples were collected to analyse markers of glucose metabolism (fasting blood glucose, haemoglobin A1c, homeostasis model assessment (HOMA-IR) as a measure of insulin resistance) and adypocytokines (adiponectin, interleukin-6, leptin, monocyte chemoattractant protein-1, retinol binding protein-4, resistin, and tumor necrosis factor-α). Participants were categorized into two groups: normoglycemia after acute pancreatitis and chronic hyperglycemia after acute pancreatitis (CHAP). Binary logistic regression and linear regression analyses were used to investigate the association between each of the adipocytokines and markers of glucose metabolism. Potential confounders were adjusted for in multivariate analyses. RESULTS: A total of 83 patients with acute pancreatitis were included, of whom 19 developed CHAP. Interleukin-6 was significantly associated with CHAP in both unadjusted and adjusted models (p = 0.030 and p = 0.018, respectively). Further, it was also significantly associated with HOMA-IR in both unadjusted and adjusted models (p = 0.029 and p = 0.037, respectively). Other adipocytokines were not significantly associated with markers of glucose metabolism. CONCLUSION: Interleukin-6 appears to be implicated in the development of chronic hyperglycemia and insulin resistance in patients after acute pancreatitis. It may become a potential target in the prevention and early treatment of diabetes after diseases of the exocrine pancreas.

Relationship between pancreatic hormones and glucose metabolism: A cross-sectional study in patients after acute pancreatitis.

Abnormal glucose metabolism is present in almost 40% of patients after acute pancreatitis, but its pathophysiology has been poorly investigated. Pancreatic hormone derangements have been sparingly studied to date, and their relationship with abnormal glucose metabolism is largely unknown. The aim was to investigate the associations between pancreatic hormones and glucose metabolism after acute pancreatitis, including the effect of potential confounders. This was a cross-sectional study of 83 adult patients after acute pancreatitis. Fasting venous blood was collected from all patients and used for analysis of insulin, glucagon, pancreatic polypeptide, amylin, somatostatin, C-peptide, glucose, and hemoglobin A1c. Statistical analyses were conducted using the modified Poisson regression, multivariable linear regression, and Spearman's correlation. Age, sex, body mass index, recurrence of acute pancreatitis, duration from first attack, severity, and etiology were adjusted for. Increased insulin was significantly associated with abnormal glucose metabolism after acute pancreatitis, in both unadjusted (P = 0.038) and adjusted (P = 0.001) analyses. Patients with abnormal glucose metabolism also had significantly decreased pancreatic polypeptide (P = 0.001) and increased amylin (P = 0.047) in adjusted analyses. Somatostatin, C-peptide, and glucagon were not changed significantly in both unadjusted and adjusted analyses. Increased insulin resistance and reduced insulin clearance may be important components of hyperinsulinemic compensation in patients after acute pancreatitis. Increased amylin and reduced pancreatic polypeptide fasting levels characterize impaired glucose homeostasis. Clinical studies investigating islet-cell hormonal responses to mixed-nutrient meal testing and euglycemic-hyperinsulinemic clamps are now warranted for further insights into the role of pancreatic hormones in glucose metabolism derangements secondary to pancreatic diseases.

Interventions That Affect Gastrointestinal Motility in Hospitalized Adult Patients: A Systematic Review and Meta-Analysis of Double-Blind Placebo-Controlled Randomized Trials.

Gastrointestinal (GI) dysmotility is a common complication in acute, critically ill, postoperative, and chronic patients that may lead to impaired nutrient delivery, poor clinical, and patient-reported outcomes. Several pharmacological and nonpharmacological interventions to treat GI dysmotility were investigated in dozens of clinical studies. However, they often yielded conflicting results, at least in part, because various (nonstandardized) definitions of GI dysmotility were used and methodological quality of studies was poor. While a universally accepted definition of GI dysmotility is yet to be developed, a systematic analysis of data derived from double-blind placebo-controlled randomized trials may provide robust data on absolute and relative effectiveness of various interventions as the study outcome (GI motility) was assessed in the least biased manner.To systematically review data from double-blind placebo-controlled randomized trials to determine and compare the effectiveness of interventions that affect GI motility.Three electronic databases (MEDLINE, SCOPUS, and EMBASE) were searched. A random effects model was used for meta-analysis. The summary estimates were reported as mean difference (MD) with the corresponding 95% confidence interval (CI).A total of 38 double-blind placebo-controlled randomized trials involving 2371 patients were eligible for inclusion in the systematic review. These studies investigated a total of 20 different interventions, of which 6 interventions were meta-analyzed. Of them, the use of dopamine receptor antagonists (MD, -8.99; 95% CI, -17.72 to -0.27; P = 0.04) and macrolides (MD, -26.04; 95% CI, -51.25 to -0.82; P = 0.04) significantly improved GI motility compared with the placebo group. The use of botulism toxin significantly impaired GI motility compared with the placebo group (MD, 5.31; 95% CI, -0.04 to 10.67; P = 0.05). Other interventions (dietary factors, probiotics, hormones) did not affect GI motility.Based on the best available data and taking into account the safety profile of each class of intervention, dopamine receptor antagonists and macrolides significantly improve GI motility and are medications of choice in treating GI dysmotility.

Impact of metabolic comorbidities on outcomes of patients with acute pancreatitis: a scoping review.

With the increasing prevalence of metabolic comorbidities, their impact on outcomes of patients with acute pancreatitis needs to be considered. Metabolic comorbidities, such as diabetes mellitus, obesity, and metabolic syndrome, have been shown to have a role to play in the course of disease. This scoping review aims to map published clinical studies that have investigated the impact of metabolic comorbidities on outcomes in patients with acute pancreatitis.

Global incidence and mortality of pancreatic diseases: a systematic review, meta-analysis, and meta-regression of population-based cohort studies.

BACKGROUND: There is a lack of robust estimates of the worldwide incidence and mortality of acute pancreatitis, chronic pancreatitis, pancreatic cysts, and pancreatic cancer in the general population. Our aim was to quantitate and compare the incidence and mortality of major pancreatic diseases in high-quality population-based cohort studies. METHODS: Three databases (PubMed, Embase, and Scopus) were searched independently by two reviewers. Data from eligible studies were subject to meta-analysis to obtain global estimates. A number of prespecified subgroup analyses and meta-regression analyses were also done. FINDINGS: 48 population-based cohort studies (35 on pancreatic cancer, ten on acute pancreatitis, three on chronic pancreatitis, and none on pancreatic cysts) were identified, with a total study population of 296 million individuals and 119 000 patients with pancreatic diseases. Global estimates of incidence and mortality were 8·14 cases (95% CI 6·63-9·98) per 100 000 person-years and 6·92 deaths (95% CI 3·72-12·89) per 100 000 person-years for pancreatic cancer, 33·74 cases (95% CI 23·33-48·81) per 100 000 person-years and 1·60 deaths (95% CI 0·85-1·58) per 100 000 person-years for acute pancreatitis, and 9·62 cases (95% CI 7·86-11·78) per 100 000 person-years and 0·09 deaths (95% CI 0·02-0·47) per 100 000 person-years for chronic pancreatitis. Subgroup analysis based on the WHO regions showed that the incidences of both pancreatic cancer and acute pancreatitis, and mortality from pancreatic cancer, were significantly higher in the American region than in the European and Western Pacific regions, while the incidence of chronic pancreatitis was significantly higher in the European region than in the American region. Mortality from pancreatic cancer was lowest in the Southeast Asian region. The incidence of chronic pancreatitis was twice as high in men as in women, although there was no difference between sexes for pancreatic cancer or acute pancreatitis. INTERPRETATION: Globally, acute pancreatitis is the most common pancreatic disease whilst pancreatic cancer is the most lethal. However, their burden is not equal across the globe. The epidemiological estimates reported in this study could inform future high-quality studies. FUNDING: None.