Yasmine Ali Abdelhamid

Pantoprazole or Placebo for Stress Ulcer Prophylaxis (pop-up): Randomized Double-blind Exploratory Study*

Objectives:Pantoprazole is frequently administered to critically ill patients for prophylaxis against gastrointestinal bleeding. However, comparison to placebo has been inadequately evaluated, and pantoprazole has the potential to cause harm. Our objective was to evaluate benefit or harm associated with pantoprazole administration. Design:Prospective randomized double-blind parallel-group study. Setting:University-affiliated mixed medical-surgical ICU. Patients:Mechanically ventilated critically ill patients suitable for enteral nutrition. Interventions:We randomly assigned patients to receive either daily IV placebo or pantoprazole. Measurements and Main Results:Major outcomes were clinically significant gastrointestinal bleeding, infective ventilator-associated complication or pneumonia, and Clostridium difficile infection; minor outcomes included overt bleeding, hemoglobin concentration profiles, and mortality. None of the 214 patients randomized had an episode of clinically significant gastrointestinal bleeding, three patients met the criteria for either an infective ventilator-associated complication or pneumonia (placebo: 1 vs pantoprazole: 2), and one patient was diagnosed with Clostridium difficile infection (0 vs 1). Administration of pantoprazole was not associated with any difference in rates of overt bleeding (6 vs 3; p = 0.50) or daily hemoglobin concentrations when adjusted for transfusion rates of packed red cells (p = 0.66). Mortality was similar between groups (log-rank p = 0.33: adjusted hazard ratio for pantoprazole: 1.68 [95% CI, 0.97–2.90]; p = 0.06). Conclusions:We found no evidence of benefit or harm with the prophylactic administration of pantoprazole to mechanically ventilated critically ill patients anticipated to receive enteral nutrition. The practice of routine administration of acid-suppressive drugs to critically ill patients for stress ulcer prophylaxis warrants further evaluation.

Effect of Critical Illness on Triglyceride Absorption

BACKGROUND Adequate nutrition support for critically ill patients optimizes outcome, and enteral feeding is the preferred route of nutrition. Small intestinal glucose absorption is frequently impaired in critical illness. Despite lipid being a major constituent of liquid nutrient administered, there is little information about lipid absorption during critical illness. OBJECTIVES To determine small intestinal lipid, as well as glucose, absorption in critical illness compared with health. MATERIALS AND METHODS Twenty-nine mechanically ventilated critically ill patients and 16 healthy volunteers were studied. Liquid nutrient (60 mL, 1 kcal/mL), containing 200 µL (13)C-triolein and 3 g 3-O-methyl-glucose (3-OMG), was infused directly into the duodenum at a rate of 2 kcal/min. Exhaled (13)CO2 and serum 3-OMG concentrations were measured at timed intervals over 360 minutes. Lipid absorption was measured as the cumulative percentage dose (cPDR) of (13)CO2 recovered at 360 minutes. Glucose absorption was measured as the area under the 3-OMG concentration curve. Data are median (range) and analyzed using the Mann-Whitney U and Pearson correlation tests. RESULTS Lipid absorption was markedly less in the critically ill (cPDR(13)CO2: patients, 22.6% [0%-100%] vs healthy participants, 40.7% [5.3%-84.7%]; P = .018). While glucose absorption was less at 60 minutes in the critically ill (3-OMG60: 13.2 [3.5-29.5] vs 21.1 [9.3-31.9] mmol/L·min; P = .003), this was not apparent at 360 minutes (3-OMG360: 92.7 [54.5-147.9] vs 107.9 [64.0-168.7] mmol/L·min; P = .126). There was no relationship between lipid and glucose absorption. CONCLUSION Small intestinal absorption of lipid is diminished during critical illness.

Nutrient stimulation of mesenteric blood flow - implications for older critically ill patients

Nutrient ingestion induces a substantial increase in mesenteric blood flow. In older persons (aged ≥ 65 years), particularly those with chronic medical conditions, the cardiovascular compensatory response may be inadequate to maintain systemic blood pressure during mesenteric blood pooling, leading to postprandial hypotension. In older ambulatory persons, postprandial hypotension is an important pathophysiological condition associated with an increased propensity for syncope, falls, coronary vascular events, stroke and death. In older critically ill patients, the administration of enteral nutrition acutely increases mesenteric blood flow, but whether this pathophysiological response is protective, or precipitates mesenteric ischaemia, is unknown. There are an increasing number of older patients surviving admission to intensive care units, who are likely to be at increased risk of postprandial hypotension, both during, and after, their stay in hospital. In this review, we describe the prevalence, impact and mechanisms of postprandial hypotension in older people and provide an overview of the impact of postprandial hypotension on feeding prescriptions in older critically ill patients. Finally, we provide evidence that postprandial hypotension is likely to be an unrecognised problem in older survivors of critical illness and discuss potential options for management.

Glycated haemoglobin is increased in critically ill patients with stress hyperglycaemia: Implications for risk of diabetes in survivors of critical illness

It remains uncertain if stress hyperglycaemia (SH) indicates a long-term predisposition to the development of type 2 diabetes. We conducted a retrospective observational study in critically ill patients and found SH to be associated with an increased HbA1c, which may indicate an increased risk of type 2 diabetes.

Antecedent hypoglycemia does not attenuate the acceleration of gastric emptying by hypoglycemia.

Context: Acute hypoglycemia accelerates gastric emptying and increases cardiac contractility. However, antecedent hypoglycemia attenuates counterregulatory hormonal responses to subsequent hypoglycemia. Objective: To determine the effect of antecedent hypoglycemia on gastric and cardiac responses to subsequent hypoglycemia in health. Design: A prospective, single‐blind, randomized, crossover study (performed at the Royal Adelaide Hospital, Adelaide, South Australia, Australia). Patients: Ten healthy young men 18 to 35 years of age were studied for 36 hours on two occasions. Interventions: Participants were randomly assigned to either antecedent hypoglycemia [three 45‐minute periods of strict hypoglycemia (2.8 mmol/L] or control [three 45‐minute periods of strict euglycemia (6 mmol/L)] during the initial 12‐hour period. Participants were monitored overnight, and the following morning blood glucose was clamped at 2.8 mmol/L for 60 minutes and then at 6 mmol/L for 120 minutes. At least 6 weeks later participants returned for the alternative intervention. Gastric emptying and cardiac fractional shortening were measured with scintigraphy and two‐dimensional echocardiography, respectively, on the morning of all 4 study days. Results: A single, acute episode of hypoglycemia accelerated gastric emptying (P = 0.01) and augmented fractional shortening (P < 0.01). Gastric emptying was unaffected by antecedent hypoglycemia (P = 0.74) whereas fractional shortening showed a trend to attenuation (P = 0.06). The adrenaline response was diminished (P < 0.05) by antecedent hypoglycemia Conclusions: In health, the acceleration of gastric emptying during hypoglycemia is unaffected by antecedent hypoglycemia, whereas the increase in cardiac contractility may be attenuated.

Postprandial hypotension in older survivors of critical illness

Purpose: In older people postprandial hypotension occurs frequently; and is an independent risk factor for falls, cardiovascular events, stroke and death. The primary aim of this pilot study was to estimate the frequency of postprandial hypotension and evaluate the mechanisms underlying this condition in older survivors of an Intensive Care Unit (ICU). Materials and methods: Thirty‐five older (>65years) survivors were studied 3months after discharge. After an overnight fast, participants consumed a 300mL drink containing 75g glucose, labelled with 20MBq 99mTc‐calcium phytate. Patients had concurrent measurements of blood pressure, heart rate, blood glucose and gastric emptying following drink ingestion. Proportion of participants is presented as percent (95% CI) and continuous variables as mean (SD). Results: Postprandial hypotension was evident in 10 (29%; 95% CI 14–44), orthostatic hypotension in 2 (6%; 95% CI 0–13) and cardiovascular autonomic dysfunction in 2 (6%; 95% CI 0–13) participants. The maximal postprandial nadir for systolic blood pressure and diastolic blood pressures were −29 (14) mmHg and −18 (7) mmHg. Conclusions: In this cohort of older survivors of ICU postprandial hypotension occurred frequently. This suggests that postprandial hypotension is an unrecognised issue in older ICU survivors. HIGHLIGHTSPostprandial hypotension is prevalent in older survivors of critical illness.Postprandial hypotension occurred more frequently than orthostatic hypotension.Symptoms of postprandial hypotension were rarely reported by patients.Postprandial hypotension may be an unrecognised problem in older ICU survivors.