The prognostic value of elevated neutrophil-lymphocyte ratio for cardiac surgery-associated acute kidney injury: A systematic review and meta-analysis.

BACKGROUND: Patients undergoing cardiac surgery are at significant risk of developing postoperative acute kidney injury (AKI). Neutrophil-lymphocyte ratio (NLR) is a widely available inflammatory biomarker which may be of prognostic value in this setting. METHODS: We conducted a systematic review and meta-analysis of studies reporting associations between perioperative NLR with postoperative AKI. We searched Medline, Embase and the Cochrane Library, without language restriction, from inception to May 2022 for relevant studies. We meta-analysed the reported odds ratios (ORs) with 95% confidence intervals (CIs) for both elevated preoperative and postoperative NLR with risk of postoperative AKI and need for renal replacement therapy (RRT). We conducted a meta-regression to explore inter-study statistical heterogeneity. RESULTS: Twelve studies involving 10,724 participants undergoing cardiac surgery were included, with eight studies being deemed at high risk of bias using PROBAST modelling. We found statistically significant associations between elevated preoperative NLR and postoperative AKI (OR 1.45, 95% CI 1.18-1.77), as well as postoperative need for RRT (OR 2.37, 95% CI 1.50-3.72). Postoperative NLR measurements were not of prognostic significance. CONCLUSIONS: Elevated preoperative NLR is a reliable inflammatory biomarker for predicting AKI following cardiac surgery.

Higher versus lower enteral calorie delivery and gastrointestinal dysfunction in critical illness: A systematic review and meta-analysis.

BACKGROUND AND AIMS: In critical illness, enteral nutrition (EN) is frequently limited by gastrointestinal (GI) dysfunction. The aim of this systematic review and meta-analysis was to determine relationships between enteral calorie delivery and GI dysfunction in critically ill adults. METHODS: MEDLINE, EMCARE, EMBASE, and CINAHL databases were searched from 1 January 2000 to 11 August 2021 to identify parallel group randomised controlled trials of an EN intervention that resulted in a significant difference in calorie delivery between groups and reported at least one outcome relating to GI dysfunction. Study groups were categorised as 'higher' or 'lower' calorie delivery and data were extracted on study interventions, GI dysfunction and clinical outcomes. Extracted data were aggregated using a random effects model and presented as risk ratio with 95% confidence intervals. A P-value <0.05 was considered significant. The risk of publication bias was assessed graphically using a funnel plot. RESULTS: From 13 studies involving 6824 patients the mean calorie delivery in the higher calorie group was 1673 ± 468 kcal/day compared to 1121 ± 312 kcal/day in the lower calorie group. The higher calorie group had an increased risk of a large (any volume ≥300 ml) gastric residual volume (GRV) (RR 1.40; 95% CI 1.09, 1.80; P = 0.009) and prokinetic administration (RR 1.18; 95% CI 1.11, 1.27; P < 0.00001). There were no between group differences in the presence of vomiting/regurgitation (RR 0.93; 95% CI 0.58, 1.49; P = 0.76), diarrhoea (RR 1.12; 95% CI 0.93, 1.35; P = 0.22) or abdominal distension (RR 0.71; 95% CI 0.49, 1.04; P = 0.08). There was no evidence of publication bias. CONCLUSION: Higher calorie delivery is associated with increased rates of GRV≥300 ml and prokinetic administration, but not vomiting/regurgitation, diarrhoea or abdominal distension. OTHER: No funding was received for the conduct of this systematic review and meta-analysis. The protocol was prospectively registered with PROSPERO (CRD42021268876).

Emerging benefits and drawbacks of α2 -adrenoceptor agonists in the management of sepsis and critical illness.

Agonists of α2 -adrenoceptors are increasingly being used for the provision of comfort, sedation and the management of delirium in critically ill patients, with and without sepsis. In this context, increased sympathetic and inflammatory activity are common pathophysiological features linked to multi-organ dysfunction, particularly in patients with sepsis or those undergoing cardiac surgery requiring cardiopulmonary bypass. Experimental and clinical studies support the notion that the α2 -adrenoceptor agonists, dexmedetomidine and clonidine, mitigate sympathetic and inflammatory overactivity in sepsis and cardiac surgery requiring cardiopulmonary bypass. These effects can protect vital organs, including the cardiovascular system, kidneys, heart and brain. We review the pharmacodynamic mechanisms by which α2 -adrenoceptor agonists might mitigate multi-organ dysfunction arising from pathophysiological conditions associated with excessive inflammatory and adrenergic stress in experimental studies. We also outline recent clinical trials that have examined the use of dexmedetomidine in critically ill patients with and without sepsis and in patients undergoing cardiac surgery.

Are Classic Bedside Exam Findings Required to Initiate Enteral Nutrition in Critically Ill Patients: Emphasis on Bowel Sounds and Abdominal Distension.

The general physical examination of a patient is an axiom of critical care medicine, but evidence to support this practice remains sparse. Given the lack of evidence for a comprehensive physical examination of the entire patient on admission to the intensive care unit, which most clinicians consider an essential part of care, should clinicians continue the practice of a specialized gastrointestinal system physical examination when commencing enteral nutrition in critically ill patients? In this review of literature related to gastrointestinal system examination in critically ill patients, the focus is on gastrointestinal sounds and abdominal distension. There is a summary of what these physical features represent, an evaluation of the evidence regarding use of these physical features in patients after abdominal surgery, exploration of the rationale for and against using the physical findings in routine practice, and detail regarding what is known about each feature in critically ill patients. Based on the available evidence, it is recommended that an isolated symptom, sign, or bedside test does not provide meaningful information. However, it is submitted that a comprehensive physical assessment of the gastrointestinal system still has a role when initiating or administering enteral nutrition: specifically, when multiple features are present, clinicians should consider further investigation or intervention.

Incretin Physiology and Pharmacology in the Intensive Care Unit.

In health, postprandial glycemic excursions are attenuated via stimulation of insulin secretion, suppression of glucagon secretion, and slowing of gastric emptying. The incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, are primary modulators of this response. Drugs have recently been developed that exploit the incretin-axis for the management of type 2 diabetes. There is burgeoning interest in the potential of incretin therapies for the management of acute hyperglycemia in the critically ill. This article outlines basic incretin physiology, highlights relevant pharmacology, and briefly summarizes the literature on incretins for glycemic control in the critically ill.

A prospective observational study of the effect of critical illness on ultrastructural and microscopic morphology of duodenal mucosa.

OBJECTIVE: Disturbed intestinal barrier function due to 'leaky' tight junctions may cause secondary sepsis via paracellular translocation across the gut wall. Our objective was to describe the effects of critical illness on duodenal morphology and ultrastructure. DESIGN, SETTING AND PARTICIPANTS: Prospective observational study of 12 mechanically ventilated critically ill patients in an intensive care unit and 15 control participants in an outpatient endoscopy suite. INTERVENTION: We took six endoscopic biopsy samples of the duodenum from each participant for analysis by electron and light microscopy. MAIN OUTCOME MEASURES: Our primary outcome was tight junction morphology, examined with electron microscopy. Secondary outcomes were microvillus length and density, vascular endothelium morphology and mitochondrial density and morphology, examined with electron microscopy, and morphology examined with light microscopy. RESULTS: We observed no abnormalities of tight junction ultrastructure in either group. There was a tendency towards shorter microvilli in the critically ill group: mean length in critically ill patients, 1.17 µm (interquartile range [IQR], 1.05-1.60 µm) v mean length in control patients, 1.58 µm (IQR, 1.30-1.72 µm); P = 0.07. There was a tendency towards less dense microvilli in the critically ill group: mean density in critically ill patients, 7.29 microvilli/µm (IQR, 6.83-8.05 microvilli/µm) v mean density in control patients, 8.23 microvilli/µm (IQR, 7.34-9.11 microvilli/µm); P = 0.07. Vascular endothelium appeared normal in all critically ill patients and abnormal in one control participant. Abnormal mitochondrial morphology was noted in one critically ill patient and one control participant, and no differences were seen in mitochondrial density. Using light microscopy, we saw more apoptotic cells in the critically ill patients (P = 0.018), but villus height, crypt depth and lymphocyte density were normal. CONCLUSIONS: We did not detect any morphological abnormalities of duodenal tight junctions in critically ill patients. Our results should be interpreted with caution because of the small sample population, but our observations challenge the concept that paracellular translocation facilitates secondary sepsis.

The insulinotropic effect of pulsatile compared with continuous intravenous delivery of GLP-1.

AIMS/HYPOTHESIS: In healthy individuals, both insulin and glucagon-like peptide 1 (GLP-1) are secreted in a pulsatile fashion. Insulin has greater glucose-lowering properties when administered in pulses compared with a constant i.v. infusion. The primary aim of this randomised double-dummy cross-over study was to compare the insulinotropic response to pulsatile and continuous i.v. infusions of equivalent doses of GLP-1. METHODS: Twelve healthy participants aged 18-35 years were randomised to three different treatments on separate days: a continuous infusion day (GLP-1 at 0.6 pmol kg(-1) min(-1) [1 ml/min] and a 1 ml placebo bolus every 6 min); a pulsatile infusion day (placebo at 1 ml/min and a 3.6 pmol/kg GLP-1 bolus every 6 min); and a placebo day (placebo at 1 ml/min and a 1 ml placebo bolus every 6 min). Between 45 and 120 min, a hyperglycaemic clamp was used to maintain blood glucose at 9 mmol/l. Venous blood glucose and plasma insulin concentrations were measured every 5 min from 0 to 45 min and every 1 min from 45 to 120 min; plasma glucagon was measured every 15 min. The order of treatment was randomised by the Pharmacy Department and both study investigators and participants were blinded to the treatment arm. The dextrose requirement and glucagon data were analysed using repeated measures ANOVA and insulin data were analysed with a linear mixed effects maximum likelihood model. RESULTS: Continuous and pulsatile infusions of GLP-1 increased the dextrose requirement by ~threefold (p < 0.001) and increased insulin secretion by ~ninefold (p < 0.001). There was no difference in the effect of both treatments. Although hyperglycaemia reduced plasma glucagon concentrations, there was no difference between the treatment days. CONCLUSIONS/INTERPRETATION: In healthy individuals, pulsatile and continuous administration of i.v. GLP-1 appears to have comparable insulinotropic effects. TRIAL REGISTRATION: ACTRN12612001040853 FUNDING: This study was supported by the National Health and Medical Research Council (NHMRC) of Australia.

Incretins and the intensivist: what are they and what does an intensivist need to know about them?

Hyperglycaemia occurs frequently in the critically ill, even in those patients without a history of diabetes. The mechanisms underlying hyperglycaemia in this group are complex and incompletely defined. In health, the gastrointestinal tract is an important modulator of postprandial glycaemic excursions and both the rate of gastric emptying and the so-called incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, are pivotal determinants of postprandial glycaemia. Incretin-based therapies (that is, glucagon-like peptide- 1 agonists and dipeptidyl-peptidase-4 inhibitors) have recently been incorporated into standard algorithms for the management of hyperglycaemia in ambulant patients with type 2 diabetes and, inevitably, an increasing number of patients who were receiving these classes of drugs prior to their acute illness will present to ICUs. This paper summarises current knowledge of the incretin effect as well as the incretin-based therapies that are available for the management of type 2 diabetes, and provides suggestions for the potential relevance of these agents in the management of dysglycaemia in the critically ill, particularly to normalise elevated blood glucose levels.