It is unclear how septic shock causes acute kidney injury (AKI) and whether this is associated with histological change.
We aimed to determine the nature and extent of changes in renal structure and ...function over time in an ovine model of septic shock.
Fifteen sheep were instrumented with a renal artery flow probe and renal vein cannula. Ten were given intravenous Escherichia coli to induce septic shock, and five acted as controls. Animals were mechanically ventilated for 48 hours, while receiving protocol-guided parenteral fluids and a norepinephrine infusion to maintain mean arterial pressure. Renal biopsies were taken every 24 hours or whenever animals were oliguric for 2 hours. A renal pathologist, blinded to tissue source, systematically quantified histological appearance by light and electron microscopy for 31 prespecified structural changes.
Sheep given E. coli developed septic shock, oliguria, increased serum creatinine, and reduced creatinine clearance (AKI), but there were no changes over time in renal blood flow between groups (P > 0.30) or over time within groups (P > 0.50). Renal oxygen consumption increased only in nonseptic animals (P = 0.01), but there was no between-group difference in renal lactate flux (P > 0.50). There was little structural disturbance in all biopsies and, although some cellular appearances changed over time, the only difference between septic and nonseptic animals was mesangial expansion on electron microscopy.
In an intensive care-supported model of gram-negative septic shock, early AKI was not associated with changes in renal blood flow, oxygen delivery, or histological appearance. Other mechanisms must contribute to septic AKI.
Sepsis remains a significant health burden and a major clinical need exists for therapeutics to dampen the excessive and uncontrolled immune activation. Nuclear protein high mobility group box ...protein 1 (HMGB1) is released following cell death and is a late mediator in sepsis pathogenesis. While approaches targeting HMGB1 have demonstrated reduced mortality in pre-clinical models of sepsis, the impact of HMGB1 blockade on the complex septic inflammatory milieu and the development of subsequent immunosuppression remain enigmatic. Analysis of plasma samples obtained from septic shock patients established an association between increased HMGB1 and non-survival, higher APACHE II scores, and increased pro-inflammatory cytokine responses. Pre-clinically, administration of neutralising ovine anti-HMGB1 polyclonal antibodies improved survival in murine endotoxaemia and caecal ligation and puncture-induced sepsis models, and altered early cytokine profiles to one which corresponded to patterns observed in the surviving patient cohort. Additionally, anti-HMGB1 treated murine sepsis survivors were significantly more resistant to secondary bacterial infection and exhibited altered innate immune cell phenotypes and cytokine responses. These findings demonstrate that anti-HMGB1 antibodies alter inflammation in murine sepsis models and reduce sepsis mortality without potentiating immunosuppression.
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 (placebo1 vs pantoprazole2), 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 = 0.33adjusted hazard ratio for pantoprazole1.68 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.
Dietary protein may attenuate the muscle atrophy experienced by patients in the ICU, yet protein handling is poorly understood. Here, Chapple et al present a study which aims to quantify protein ...digestion and amino acid absorption and fasting and postprandial myofibrillar protein synthesis during critical illness. They conclude that the capacity for critically ill patients to use ingested protein for muscle protein synthesis is markedly blunted despite relatively normal protein digestion and amino acid absorption.
Nutrition intake in the post-ICU hospitalization period Ridley, Emma J; Chapple, Lee-anne S; Chapman, Marianne J
Current opinion in clinical nutrition and metabolic care,
2020-March, 2020-03-00, 20200301, Letnik:
23, Številka:
2
Journal Article
Recenzirano
PURPOSE OF REVIEWThe care of critically ill patients has evolved over recent years, resulting in significant reductions in mortality in developed countries; sometimes with prolonged issues with ...recovery. Nutrition research has focused on the early, acute period of critical illness, until more recently, where the post-ICU hospitalization period in critical care survivors has become a focus for nutrition rehabilitation. In this period, nutrition rehabilitation may be a vital component of recovery.
RECENT FINDINGSOverall, oral nutrition is the most common mode of nutrition provision in the post-ICU period. Compared with oral intake alone, calorie and protein requirements can be better met with the addition of oral supplements and/or enteral nutrition to oral intake. However, calorie and protein intake remains below predicted targets in the post-ICU hospitalization period. Achieving nutrition targets are complex and multifactorial, but can primarily be grouped into three main areaspatient factors; clinician factors; and system factors.
SUMMARYA nutrition intervention in the post-ICU hospitalization period may provide an opportunity to improve survival and functional recovery. However, there are multiple barriers to the delivery of calculated nutrition requirements in this period, a limited understanding of how this can be improved and how this translates into clinical benefit.
Acute administration of glucagon-like peptide 1 (GLP-1) and its agonists slows gastric emptying, which represents the major mechanism underlying their attenuation of postprandial glycemic excursions. ...However, this effect may diminish during prolonged use. We compared the effects of prolonged and intermittent stimulation of the GLP-1 receptor on gastric emptying and glycemia. Ten healthy men received intravenous saline (placebo) or GLP-1 (0.8 pmol/kg ⋅ min), as a continuous 24-h infusion ("prolonged"), two 4.5-h infusions separated by 20 h ("intermittent"), and a 4.5-h infusion ("acute") in a randomized, double-blind, crossover fashion. Gastric emptying of a radiolabeled mashed potato meal was measured using scintigraphy. Acute GLP-1 markedly slowed gastric emptying. The magnitude of the slowing was attenuated with prolonged but maintained with intermittent infusions. GLP-1 potently diminished postprandial glycemia during acute and intermittent regimens. These observations suggest that short-acting GLP-1 agonists may be superior to long-acting agonists when aiming specifically to reduce postprandial glycemic excursions in the treatment of type 2 diabetes.
Neuraminidase inhibitors are effective for the treatment of acute uncomplicated influenza. However, there is an unmet need for intravenous treatment for patients admitted to hospital with severe ...influenza. We studied whether intravenous zanamivir was a suitable treatment in this setting.
In this international, randomised, double-blind, double-dummy, phase 3 trial, we recruited patients aged 16 years or older with severe influenza admitted to 97 hospitals from 26 countries. We randomly assigned patients (1:1:1 stratified by symptom onset ≤4 days or 5-6 days) to receive 300 mg or 600 mg intravenous zanamivir, or standard-of-care (75 mg oral oseltamivir) twice a day for 5-10 days; patients were followed up for 28 days. The randomisation schedule, including stratification, was generated using GlaxoSmithKline's RandAll software. Patients, site study staff, and sponsor were masked to study treatment. The primary endpoint was time to clinical response-a composite of vital sign stabilisation and hospital discharge-in the influenza-positive population. The trial was powered to show an improvement of 1·5 days or greater with 600 mg intravenous zanamivir. Pharmacokinetic, safety, and virology endpoints were also assessed. This trial is registered with ClinicalTrials.gov, number NCT01231620.
Between Jan 15, 2011, and Feb 12, 2015, 626 patients were randomly assigned to receive 300 mg intravenous zanamivir (n=201), 600 mg intravenous zanamivir (n=209), or 75 mg oral oseltamivir (n=205) twice a day; 11 patients discontinued the study before receiving any study treatment. 488 (78%) of 626 patients had laboratory-confirmed influenza. Compared with a median time to clinical response of 5·14 days in the 600 mg intravenous zanamivir group, the median time to clinical response was 5·87 days (difference of -0·73 days, 95% CI -1·79 to 0·75; p=0·25) in the 300 mg intravenous zanamivir group and 5·63 days (difference of -0·48 days, 95% CI -2·11 to 0·97; p=0·39) in the oseltamivir group. Four patients with influenza A/H1N1pdm09 in the oseltamivir group developed H275Y resistance mutations. Adverse events were reported in 373 (61%) of treated patients and were similar across treatment groups; the most common adverse events (300 mg intravenous zanamivir, 600 mg intravenous zanamivir, oseltamivir) were diarrhoea (10 5%, 15 7%, 14 7%), respiratory failure (11 5%, 14 7%, 11 5%), and constipation (7 3%, 13 6%, 10 5%). 41 (7%) treated patients died during the study (15 7%, 15 7%, 11 5%); the most common causes of death were respiratory failure and septic shock.
Time to clinical response to intravenous zanamivir dosed at 600 mg was not superior to oseltamivir or 300 mg intravenous zanamivir. All treatments had a similar safety profile in hospitalised patients with severe influenza.
GlaxoSmithKline.
Purpose
Hyperglycaemia is common in the critically ill. The objectives of this study were to determine the prevalence of critical illness-associated hyperglycaemia (CIAH) and recognised and ...unrecognised diabetes in the critically ill as well as to evaluate the impact of premorbid glycaemia on the association between acute hyperglycaemia and mortality.
Methods
In 1,000 consecutively admitted patients we prospectively measured glycated haemoglobin (HbA
1c
) on admission, and blood glucose concentrations during the 48 h after admission, to the intensive care unit. Patients with blood glucose ≥7.0 mmol/l when fasting or ≥11.1 mmol/l during feeding were deemed hyperglycaemic. Patients with acute hyperglycaemia and HbA
1c
<6.5 % (48 mmol/mol) were categorised as ‘CIAH’, those with known diabetes as ‘recognised diabetes’, and those with HbA
1c
≥6.5 % but no previous diagnosis of diabetes as ‘unrecognised diabetes’. The remainder were classified as ‘normoglycaemic’. Hospital mortality, HbA
1c
and acute peak glycaemia were assessed using a logistic regression model.
Results
Of 1,000 patients, 498 (49.8 %) had CIAH, 220 (22 %) had recognised diabetes, 55 (5.5 %) had unrecognised diabetes and 227 (22.7 %) were normoglycaemic. The risk of death increased by approximately 20 % for each increase in acute glycaemia of 1 mmol/l in patients with CIAH and those with diabetes and HbA
1c
levels <7 % (53 mmol/mol), but not in patients with diabetes and HbA
1c
≥7 %. This association was lost when adjusted for severity of illness.
Conclusions
Critical illness-associated hyperglycaemia is the most frequent cause of hyperglycaemia in the critically ill. Peak glucose concentrations during critical illness are associated with increased mortality in patients with adequate premorbid glycaemic control, but not in patients with premorbid hyperglycaemia. Optimal glucose thresholds in the critically ill may, therefore, be affected by premorbid glycaemia.
Gastrointestinal dysmotility causes delayed gastric emptying, enteral feed intolerance, and functional obstruction of the small and large intestine, the latter functional obstructions being ...frequently termed ileus and Ogilvie syndrome, respectively. In addition to meticulous supportive care, drug therapy may be appropriate in certain situations. There is, however, considerable variation among individuals regarding what gastric residual volume identifies gastric dysmotility and would encourage use of a promotility drug. While the administration of either metoclopramide or erythromycin is supported by evidence it appears that, dual‐drug therapy (erythromycin and metoclopramide) reduces the rate of treatment failure. There is a lack of evidence to guide drug therapy of ileus, but neither erythromycin nor metoclopramide appear to have a role. Several drugs, including ghrelin agonists, highly selective 5‐hydroxytryptamine receptor agonists, and opiate antagonists are being studied in clinical trials. Neostigmine, when infused at a relatively slow rate in patients receiving continuous hemodynamic monitoring, may alleviate the need for endoscopic decompression in some patients.
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