A Randomized Noninferiority Trial to Compare Enteral to Parenteral Phosphate Replacement on Biochemistry, Waste, and Environmental Impact and Healthcare Cost in Critically Ill Patients With Mild to Moderate Hypophosphatemia.

OBJECTIVES: Hypophosphatemia occurs frequently. Enteral, rather than IV, phosphate replacement may reduce fluid replacement, cost, and waste. DESIGN: Prospective, randomized, parallel group, noninferiority clinical trial. SETTING: Single center, 42-bed state trauma, medical and surgical ICUs, from April 20, 2022, to July 1, 2022. PATIENTS: Patients with serum phosphate concentration between 0.3 and 0.75 mmol/L. INTERVENTIONS: We randomized patients to either enteral or IV phosphate replacement using electronic medical record-embedded program. MEASUREMENT AND MAIN RESULTS: Our primary outcome was serum phosphate at 24 hours with a noninferiority margin of 0.2 mmol/L. Secondary outcomes included cost savings and environmental waste reduction and additional IV fluid administered. The modified intention-to-treat cohort comprised 131 patients. Baseline phosphate concentrations were similar between the two groups. At 24 hours, mean ( sd ) serum phosphate concentration were enteral 0.89 mmol/L (0.24 mmol/L) and IV 0.82 mmol/L (0.28 mmol/L). This difference was noninferior at the margin of 0.2 mmol/L (difference, 0.07 mmol/L; 95% CI, -0.02 to 0.17 mmol/L). When assigned IV replacement, patients received 408 mL (372 mL) of solvent IV fluid. Compared with IV replacement, the mean cost per patient was ten-fold less with enteral replacement ($3.7 [$4.0] vs. IV: $37.7 [$31.4]; difference = $34.0 [95% CI, $26.3-$41.7]) and weight of waste was less (7.7 g [8.3 g] vs. 217 g [169 g]; difference = 209 g [95% CI, 168-250 g]). C O2 emissions were 60-fold less for comparable phosphate replacement (enteral: 2 g producing 14.2 g and 20 mmol of potassium dihydrogen phosphate producing 843 g of C O2 equivalents). CONCLUSIONS: Enteral phosphate replacement in ICU is noninferior to IV replacement at a margin of 0.2 mmol/L but leads to a substantial reduction in cost and waste.

Perioperative management of long-acting glucagon-like peptide-1 (GLP-1) receptor agonists: concerns for delayed gastric emptying and pulmonary aspiration.

Prescriptions and use of glucagon-like peptide-1 (GLP-1) receptor agonists are increasing dramatically, as indications are expanding from the treatment of diabetes mellitus to weight loss for people with obesity. As GLP-1 receptor agonists delay gastric emptying, perioperative healthcare practitioners could be concerned about an increased risk for pulmonary aspiration during general anaesthesia. We summarise relevant medical literature and provide evidence-based recommendations for perioperative care for people taking GLP-1 receptor agonists. GLP-1 receptor agonists delay gastric emptying; however, ongoing treatment attenuates this effect. The risk of aspiration during general anaesthesia is unknown. However, we advise caution in patients who recently commenced on GLP-1 receptor agonists. After over 12 weeks of treatment, standard fasting times likely suffice to manage the risk of pulmonary aspiration for most otherwise low-risk patients.

Models of intensive care unit follow-up care and feasibility of intervention delivery: A systematic review.

BACKGROUND: The optimal model of outpatient intensive care unit (ICU) follow-up care remains uncertain, and there is limited evidence of benefit. RESEARCH QUESTION: The objective of this research is to describe existing models of outpatient ICU follow-up care, quantify participant recruitment and retention, and describe facilitators of patient engagement. STUDY DESIGN & METHODS: A systematic search of the MEDLINE and EMBASE databases was undertaken in June 2021. Two independent reviewers screened titles, abstracts, and full texts against eligibility criteria. Studies of adults with any outpatient ICU follow-up were included. Studies were excluded if published before 1990, not published in English, or of paediatric patients. Quantitative data were extracted using predefined data fields. Key themes were extracted from qualitative studies. Risk of bias was assessed. RESULTS: A total of 531 studies were screened. Forty-seven studies (32 quantitative and 15 qualitative studies) with a total of 5998 participants were included. Of 33 quantitative study interventions, the most frequently reported model of care was in-person hospital-based interventions (n = 27), with 10 hybrid (part in-hospital, part remote) interventions. Literature was limited for interventions without hospital attendance (n = 6), including telehealth and diaries. The median ranges of rates of recruitment, rates of intervention delivery, and retention to outcome assessment for hospital-based interventions were 51.5% [24-94%], 61.9% [8-100%], and 52% [8.1-82%], respectively. Rates were higher for interventions without hospital attendance: 82.6% [60-100%], 68.5% [59-89%], and 75% [54-100%]. Facilitators of engagement included patient-perceived value of follow-up, continuity of care, intervention accessibility and flexibility, and follow-up design. Studies had a moderate risk of bias. INTERPRETATION: Models of post-ICU care without in-person attendance at the index hospital potentially have higher rates of recruitment, intervention delivery success, and increased participant retention when compared to hospital-based interventions. PROSPERO REGISTRATION: CRD42021260279.

In-person peer support for critical care survivors: The ICU REcovery Solutions cO-Led through surVivor Engagement (ICURESOLVE) pilot randomised controlled trial.

BACKGROUND: Peer support is a promising intervention to mitigate post-ICU disability, however there is a paucity of rigorously designed studies. OBJECTIVES: The objective of this study was to establish feasibility of an in-person, co-designed, peer-support model. METHODS: Prospective, randomised, adaptive, single-centre pilot trial with blinded outcome assessment, conducted at a university-affiliated hospital in Melbourne, Australia. Intensive care unit survivors (and their nominated caregiver, where survivor and caregiver are referred to as a dyad), >18 years of age, able to speak and understand English and participate in phone surveys, were eligible. Participants were randomised to the peer-support model (six sessions, fortnightly) or usual care (no follow-up or targeted information). Two sequential models were piloted: 1. Early (2-3 weeks post hospital discharge) 2. Later (4-6 weeks post hospital discharge). Primary outcome was feasibility of implementation measured by recruitment, intervention attendance, and outcome completion. Secondary outcomes included post-traumatic stress and social support. RESULTS: Of the 231 eligible patients, 80 participants were recruited. In the early model we recruited 38 participants (28 patients, 10 carers; 18 singles, 10 dyads), with an average (standard deviation) age of 60 (18) years; 55 % were female. Twenty-two participants (58 %) were randomised to intervention. Participants in the early intervention model attended a median (interquartile range) of 0 (0-1) sessions (total 24 sessions), with 53% (n = 20) completing the main secondary outcome of interest (Impact of Event Scale) at the baseline and 37 % (n = 14) at the follow-up. For the later model we recruited 42 participants (32 patients, 10 carers; 22 singles, 10 dyads), with an average (standard deviation) age of 60.4 (15.4) years; 50 % were female. Twenty-one participants (50 %) were randomised to intervention. The later intervention model attended a median (interquartile range) of 1 (0-5) sessions (total: 44 sessions), with the main secondary outcome impact of events scale (IES-R) completed by 41 (98 %) participants at baseline and 29 (69 %) at follow-up. CONCLUSIONS: In this pilot trial, a peer-support model that required in-person attendance delivered in a later posthospital phase of recovery appeared more feasible than an early model. Further research should investigate alternative modes of intervention delivery to improve feasibility (ACTRN12621000737831).

Gastrointestinal function in critically ill patients.

PURPOSE OF REVIEW: To summarize recent evidence regarding the diagnosis of acute gastrointestinal dysfunction and enteral feeding intolerance, and relationship of these to development of multiple organ dysfunction syndrome, during critical illness. RECENT FINDINGS: Novel gastric feeding tubes that attenuate gastroesophageal regurgitation or facilitate continuous monitoring of gastric motility have been developed. The definition of enteral feeding intolerance remains controversial, which may be resolved using a consensus process. A novel scoring system for gastrointestinal dysfunction (GIDS - GastroIntestinal Dysfunction Score) was recently developed but it is not yet validated or tested to evaluate the effect of any interventions. Studies of biomarkers to identify gastrointestinal dysfunction have yet to yield a suitable biomarker for daily clinical use. SUMMARY: The assessment of gastrointestinal function in critically ill patients continues to rely on complex daily clinical assessment. Scoring systems, consensus definitions and novel technology appear the most promising tools and interventions to improve patient care.

Clearance of Piperacillin-Tazobactam and Vancomycin During Continuous Renal Replacement With Regional Citrate Anticoagulation.

BACKGROUND: The use of regional citrate anticoagulation during continuous venovenous hemodiafiltration (CVVHDF) has increased worldwide. However, data on its effect on the pharmacokinetics of antibiotics are limited. In this study, the authors aimed to measure the clearance of piperacillin-tazobactam and vancomycin in patients receiving CVVHDF with regional citrate anticoagulation. METHODS: This study measured piperacillin-tazobactam and vancomycin concentrations in patients receiving CVVHDF with regional citrate anticoagulation. Dosing regimens were independently selected by intensivists. Arterial blood and effluent fluid samples were obtained over a single dosing interval and analyzed using ultra-high-performance liquid chromatography with tandem mass spectrometry. RESULTS: Seventeen sampling intervals in 15 patients (9 receiving piperacillin-tazobactam only, 4 receiving vancomycin only, and 2 receiving both) were used. The median overall clearance for piperacillin was 35.2 mL/min [interquartile range (IQR): 32.2-38.6], 70 mL/min (IQR: 62.7-76.2) for tazobactam, and 29.5 mL/min (IQR: 26.2-32) for vancomycin. CONCLUSIONS: This is the first study to quantify the pharmacokinetics of vancomycin and piperacillin-tazobactam in patients receiving CVVHDF with regional citrate anticoagulation. These results indicate high clearance and provide key information to guide optimal dosing.

Initiating angiotensin II at lower vasopressor doses in vasodilatory shock: an exploratory post-hoc analysis of the ATHOS-3 clinical trial.

BACKGROUND: High dose vasopressors portend poor outcome in vasodilatory shock. We aimed to evaluate the impact of baseline vasopressor dose on outcomes in patients treated with angiotensin II (AT II). METHODS: Exploratory post-hoc analysis of the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) trial data. The ATHOS-3 trial randomized 321 patients with vasodilatory shock, who remained hypotensive (mean arterial pressure of 55-70 mmHg) despite receiving standard of care vasopressor support at a norepinephrine-equivalent dose (NED) > 0.2 µg/kg/min, to receive AT II or placebo, both in addition to standard of care vasopressors. Patients were grouped into low (≤ 0.25 µg/kg/min; n = 104) or high (> 0.25 µg/kg/min; n = 217) NED at the time of study drug initiation. The primary outcome was the difference in 28-day survival between the AT II and placebo subgroups in those with a baseline NED ≤ 0.25 µg/kg/min at the time of study drug initiation. RESULTS: Of 321 patients, the median baseline NED in the low-NED subgroup was similar in the AT II (n = 56) and placebo (n = 48) groups (median of each arm 0.21 µg/kg/min, p = 0.45). In the high-NED subgroup, the median baseline NEDs were also similar (0.47 µg/kg/min AT II group, n = 107 vs. 0.45 µg/kg/min placebo group, n = 110, p = 0.75). After adjusting for severity of illness, those randomized to AT II in the low-NED subgroup were half as likely to die at 28-days compared to placebo (HR 0.509; 95% CI 0.274-0.945, p = 0.03). No differences in 28-day survival between AT II and placebo groups were found in the high-NED subgroup (HR 0.933; 95% CI 0.644-1.350, p = 0.71). Serious adverse events were less frequent in the low-NED AT II subgroup compared to the placebo low-NED subgroup, though differences were not statistically significant, and were comparable in the high-NED subgroups. CONCLUSIONS: This exploratory post-hoc analysis of phase 3 clinical trial data suggests a potential benefit of AT II introduction at lower doses of other vasopressor agents. These data may inform design of a prospective trial. TRIAL REGISTRATION: The ATHOS-3 trial was registered in the clinicaltrials.gov repository (no. NCT02338843). Registered 14 January 2015.

Muscle Protein Synthesis after Protein Administration in Critical Illness.

Rationale: Dietary protein may attenuate the muscle atrophy experienced by patients in the ICU, yet protein handling is poorly understood. Objectives: To quantify protein digestion and amino acid absorption and fasting and postprandial myofibrillar protein synthesis during critical illness. Methods: Fifteen mechanically ventilated adults (12 male; aged 50 ± 17 yr; body mass index, 27 ± 5 kg⋅m-2) and 10 healthy control subjects (6 male; 54 ± 23 yr; body mass index, 27 ± 4 kg⋅m-2) received a primed intravenous L-[ring-2H5]-phenylalanine, L-[3,5-2H2]-tyrosine, and L-[1-13C]-leucine infusion over 9.5 hours and a duodenal bolus of intrinsically labeled (L-[1-13C]-phenylalanine and L-[1-13C]-leucine) intact milk protein (20 g protein) over 60 minutes. Arterial blood and muscle samples were taken at baseline (fasting) and for 6 hours following duodenal protein administration. Data are mean ± SD, analyzed with two-way repeated measures ANOVA and independent samples t test. Measurements and Main Results: Fasting myofibrillar protein synthesis rates did not differ between ICU patients and healthy control subjects (0.023 ± 0.013% h-1 vs. 0.034 ± 0.016% h-1; P = 0.077). After protein administration, plasma amino acid availability did not differ between groups (ICU patients, 54.2 ± 9.1%, vs. healthy control subjects, 61.8 ± 13.1%; P = 0.12), and myofibrillar protein synthesis rates increased in both groups (0.028 ± 0.010% h-1 vs. 0.043 ± 0.018% h-1; main time effect P = 0.046; P-interaction = 0.584) with lower rates in ICU patients than in healthy control subjects (main group effect P = 0.001). Incorporation of protein-derived phenylalanine into myofibrillar protein was ∼60% lower in ICU patients (0.007 ± 0.007 mol percent excess vs. 0.017 ± 0.009 mol percent excess; P = 0.007). Conclusions: 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.

The Effect of a Liberal Approach to Glucose Control in Critically Ill Patients with Type 2 Diabetes: A Multicenter, Parallel-Group, Open-Label Randomized Clinical Trial.

Rationale: Blood glucose concentrations affect outcomes in critically ill patients, but the optimal target blood glucose range in those with type 2 diabetes is unknown. Objectives: To evaluate the effects of a "liberal" approach to targeted blood glucose range during ICU admission. Methods: This mutlicenter, parallel-group, open-label randomized clinical trial included 419 adult patients with type 2 diabetes expected to be in the ICU on at least three consecutive days. In the intervention group intravenous insulin was commenced at a blood glucose >252 mg/dl and titrated to a target range of 180-252 mg/dl. In the comparator group insulin was commenced at a blood glucose >180 mg/dl and titrated to a target range of 108-180 mg/dl. The primary outcome was incident hypoglycemia (<72 mg/dl). Secondary outcomes included glucose metrics and clinical outcomes. Measurements and Main Results: By Day 28, at least one episode of hypoglycemia occurred in 10 of 210 (5%) patients assigned the intervention and 38 of 209 (18%) patients assigned the comparator (incident rate ratio, 0.21 [95% confidence interval (CI), 0.09 to 0.49]; P < 0.001). Those assigned the intervention had greater blood glucose concentrations (daily mean, minimum, maximum), less glucose variability, and less relative hypoglycemia (P < 0.001 for all comparisons). By Day 90, 62 of 210 (29.5%) in the intervention and 52 of 209 (24.9%) in the comparator group had died (absolute difference, 4.6 percentage points [95% CI, -3.9% to 13.2%]; P = 0.29). Conclusions: A liberal approach to blood glucose targets reduced incident hypoglycemia but did not improve patient-centered outcomes. Clinical trial registered with Australian New Zealand Clinical Trials Registry (ACTRN 12616001135404).

Relationship of blood thiamine pyrophosphate to plasma phosphate and the response to enteral nutrition plus co-administration of intravenous thiamine during critical illness.

BACKGROUND: Hypovitamin B1 occurs frequently during critical illness but is challenging to predict or rapidly diagnose. The aim of this study was to evaluate whether plasma phosphate concentrations predict hypovitamin B1, enteral nutrition prevents hypovitamin B1 and intravenous thiamine supplementation achieves supraphysiological concentrations in critically ill patients. METHODS: Thirty-two enterally fed critically ill patients, with a plasma phosphate concentration ≤0.65 mmol/L, formed a nested cohort within a larger randomised clinical trial. Patients were assigned to receive intravenous thiamine (200 mg) twice daily, and controls were not administered intravenous thiamine. Thiamine pyrophosphate concentrations were measured at four time points (pre- and post-infusion and 4- and 6-h post-infusion) on days 1 and 3 in those allocated to thiamine and once in the control group. RESULTS: Baseline thiamine pyrophosphate concentrations were similar (intervention 88 [67, 93] vs. control 89 [62, 110] nmol/L, p = 0.49). Eight (25%) patients had hypovitamin B1 (intervention 3 vs. control 5), with two patients in the control group remaining insufficient at day 3. There was no association between baseline phosphate and thiamine pyrophosphate concentrations. Intravenous thiamine achieved supraphysiological concentrations 6 h post first infusion, with concentrations increasing to day 3. In the control group, thiamine pyrophosphate concentrations were not statistically different between baseline and day 3 (mean change: 8.6 [-6.0, 23.1] nmol/L, p = 0.25). CONCLUSIONS: Phosphate concentrations did not predict hypovitamin B1, which was observed in 25% of the participants. Enteral nutrition alone prevented the development of new hypovitamin B1. Administration of a single 200-mg dose of intravenous thiamine achieved supraphysiological concentrations of thiamine pyrophosphate, with repeated dosing sustaining this effect.

Diabetes mellitus, glycaemic control, and severe COVID-19 in the Australian critical care setting: A nested cohort study.

BACKGROUND: Internationally, diabetes mellitus is recognised as a risk factor for severe COVID-19. The relationship between diabetes mellitus and severe COVID-19 has not been reported in the Australian population. OBJECTIVE: The objective of this study was to determine the prevalence of and outcomes for patients with diabetes admitted to Australian intensive care units (ICUs) with COVID-19. METHODS: This is a nested cohort study of four ICUs in Melbourne participating in the Short Period Incidence Study of Severe Acute Respiratory Infection (SPRINT-SARI) Australia project. All adult patients admitted to the ICU with COVID-19 from 20 February 2020 to 27 February 2021 were included. Blood glucose and glycated haemoglobin (HbA1c) data were retrospectively collected. Diabetes was diagnosed from medical history or an HbA1c ≥6.5% (48 mmol/mol). Hospital mortality was assessed using logistic regression. RESULTS: There were 136 patients with median age 58 years [48-68] and median Acute Physiology and Chronic Health Evaluation II (APACHE II) score of 14 [11-19]. Fifty-eight patients had diabetes (43%), 46 patients had stress-induced hyperglycaemia (34%), and 32 patients had normoglycaemia (23%). Patients with diabetes were older, were with higher APACHE II scores, had greater glycaemic variability than patients with normoglycaemia, and had longer hospital length of stay. Overall hospital mortality was 16% (22/136), including nine patients with diabetes, nine patients with stress-induced hyperglycaemia, and two patients with normoglycaemia. CONCLUSION: Diabetes is prevalent in patients admitted to Australian ICUs with severe COVID-19, highlighting the need for prevention strategies in this vulnerable population.

Is it time to personalise glucose targets during critical illness?

PURPOSE OF REVIEW: Dysglycaemia complicates most critical care admissions and is associated with harm, yet glucose targets, particularly in those with preexisting diabetes, remain controversial. This review will summarise advances in the literature regarding personalised glucose targets in the critically ill. RECENT FINDINGS: Observational data suggest that the degree of chronic hyperglycaemia in critically ill patients with diabetes attenuates the relationship between mortality and several metrics of dysglycaemia, including blood glucose on admission, and mean blood glucose, glycaemic variability and hypoglycaemia in the intensive care unit. The interaction between acute and chronic hyperglycaemia has recently been quantified with novel metrics of relative glycaemia including the glycaemic gap and stress hyperglycaemia ratio. Small pilot studies provided preliminary data that higher blood glucose thresholds in critically ill patients with chronic hyperglycaemia may reduce complications of intravenous insulin therapy as assessed with biomakers. Although personalising glycaemic targets based on preexisting metabolic state is an appealing concept, the recently published CONTROLLING trial did not identify a mortality benefit with individualised glucose targets, and the effect of personalised glucose targets on patient-centred outcomes remains unknown. SUMMARY: There is inadequate data to support adoption of personalised glucose targets into care of critically ill patients. However, there is a strong rationale empowering future trials utilising such an approach for patients with chronic hyperglycaemia.

Update on glucose control during and after critical illness.

PURPOSE OF REVIEW: There is a complex bidirectional relationship between critical illness and disordered glucose metabolism. This review aims to provide a comprehensive summary of the recent evidence focused on the relationship between critical illness and disordered glucose metabolism through the distinct phases of prior to, during, and after an acute illness that requires admission to the intensive care unit (ICU). RECENT FINDINGS: Recent data suggest that preexisting glucose metabolism affects the optimal blood glucose target during critical illness, with preliminary data suggesting that glucose targets should be 'personalized' based on preexisting glycemia. Because of the close association between critical illness and disordered glucose metabolism, there is a need to optimize glucose monitoring in the ICU with rapid, precise, and cost-efficient measurements at the bedside. Recent studies have evaluated the use of various methodologies, with a focus on the use of near-continuous glucose monitoring. For those patients with preexisting diabetes who survive ICU, nocturnal hypoglycemia may be an unrecognized and important issue when discharged to the ward. There is increasing evidence that patients with high blood glucose during their acute illness, so called 'stress hyperglycemia', are at increased risk of developing diabetes in the years following recovery from the inciting event. Critically ill patients with COVID-19 appear at greater risk. SUMMARY: There have been important recent insights in the approach to glucose monitoring and glucose targets during critical illness, monitoring and administration of glucose-lowering drugs on discharge from the ICU, and longitudinal follow-up of patients with stress hyperglycemia.

Administration of pharmacological sleep aids prior to, during and following critical illness.

BACKGROUND: Sleep in the intensive care unit (ICU) is frequently disturbed and this may have a detrimental effect on recovery. AIM: To determine the use of pharmacological sleep aids in critically ill patients prior to, during and after ICU admission. METHODS: We conducted a single-centre period prevalence study of all adult patients admitted to a university-associated adult medical-surgical ICU for more than two nights in a 3-month period ending September 2019. The major outcome of interest was the proportion of ICU patients who had a pharmacological sleep aid administered prior to, during and after ICU admission. Associations of selected patient variables with sleep aid prescription in the ICU were summarised both as unadjusted univariable comparisons and as adjusted effect estimates returned by a multivariable logistic regression model. RESULTS: During the study period, 370 patients met all eligibility criteria. A pharmacological sleep aid was identified prior to hospital admission in 34 (9%) patients and in 62 (17%) patients during ICU admission. Of the 340 ICU survivors, 292 remained in the same hospital. Of these, 96 (33%) received a pharmacological sleep aid at least once during their post-ICU general hospital ward stay. Pre-hospital sleep aid use, male sex, longer ICU admission and higher APACHE (Acute Physiology and Chronic Health Evaluation) III scores were associated with sleep aid prescription in the ICU. CONCLUSIONS: Pharmacological sleep aids are administered frequently in the ICU with administration increasing substantially after ICU discharge.

The impact of a modified carbohydrate formula, and its constituents, on glycaemic control and inflammatory markers: A nested mechanistic sub-study.

BACKGROUND: Hyperglycaemia occurs frequently in the critically ill. Dietary intake of advanced glycation end-products (AGEs), specifically Nε-(carboxymethyl)lysine (CML), may exacerbate hyperglycaemia through perturbation of insulin sensitivity. The present study aimed to determine whether the use of nutritional formulae, with varying AGE loads, affects the amount of insulin administered and inflammation. METHODS: Exclusively tube fed patients (n = 35) were randomised to receive Nutrison Protein Plus Multifibre®, Diason® or Glucerna Select®. Insulin administration was standardised according to protocol based on blood glucose (<10 mmol L-1 ). Samples were obtained at randomisation and 48 h later. AGEs in nutritional formula, plasma and urine were measured using mass spectrometry. Plasma inflammatory markers were measured using an enzyme-linked immunosorbent assay and multiplex bead-based assays. RESULTS: AGE concentrations of CML in nutritional formulae were greatest with delivery of Nutrison Protein Plus® (mean [SD]; 6335 pmol mol-1 [2436]) compared to Diason® (4836 pmol mol-1 [1849]) and Glucerna Select® (4493 pmol mol-1 [1829 pmol mol-1 ]) despite patients receiving similar amounts of energy (median [interquartile range]; 12 MJ [8.2-13.7 MJ], 11.5 MJ [8.3-14.5 MJ], 11.5 MJ [8.3-14.5 MJ]). More insulin was administered with Nutrison Protein Plus® (2.47 units h-1 [95% confidence interval (CI) = 1.57-3.37 units h-1 ]) compared to Diason® (1.06 units h-1 [95% CI = 0.24-1.89 units h-1 ]) or Glucerna Select® (1.11 units h-1 [95% CI = 0.25-1.97 units h-1 ]; p = 0.04). Blood glucose concentrations were similar. There were associations between greater insulin administration and reductions in circulating interleukin-6 (r = -0.46, p < 0.01), tumour necrosis factor-α (r = -0.44, p < 0.05), high sensitivity C-reactive protein (r = -0.42, p < 0.05) and soluble receptor for advanced glycation end-products (r = -0.45, p < 0.01) concentrations. CONCLUSIONS: The administration of greater AGE load in nutritional formula potentially increases the amount of insulin required to maintain blood glucose within a normal range during critical illness. There was an inverse relationship between exogenous insulin and plasma inflammatory markers.

The use of smartphone-derived location data to evaluate participation following critical illness: A pilot observational cohort study.

BACKGROUND: Disability is common following critical illness, impacting the quality of life of survivors, and is difficult to measure. 'Participation' can be quantified as involvement in life outside of their home requiring movement from their home to other locations. Participation restriction is a key element of disability, and following critical illness, participation may be diminished. It may be possible to quantify this change using pre-existing smartphone data. OBJECTIVES: The feasibility of extracting location data from smartphones of survivors of intensive care unit (ICU) admission and assessing participation, using location-based outcomes, during recovery from critical illness was evaluated. METHODS: Fifty consecutively admitted, consenting adult survivors of non-elective admission to ICU of greater than 48-h duration were recruited to a prospective observational cohort study where they were followed up at 3 and 6 months following discharge. The feasibility of extracting location data from survivors' smartphones and creating location-derived outcomes assessing participation was investigated over three 28-d study periods: pre-ICU admission and at 3 and 6 months following discharge. The following were calculated: time spent at home; the number of destinations visited; linear distance travelled; and two 'activity spaces', a minimum convex polygon and standard deviation ellipse. RESULTS: Results are median [interquartile range] or n (%). The number of successful extractions was 9/50 (18%), 12/39 (31%), and 13/33 (39%); the percentage of time spent at home was 61 [56-68]%, 77 [66-87]%, and 67 [58-77]% (P = 0.16); the number of destinations visited was 34 [18-64], 38 [22-63], and 65 [46-88] (P = 0.02); linear distance travelled was 367 [56-788], 251 [114-323], and 747 [326-933] km over 28 d (P = 0.02), pre-ICU admission and at 3 and 6 months following ICU discharge, respectively. Activity spaces were successfully created. CONCLUSION: Limited smartphone ownership, missing data, and time-consuming data extraction limit current implementation of mass extraction of location data from patients' smartphones to aid prognostication or measure outcomes. The number of journeys taken and the linear distance travelled increased between 3 and 6 months, suggesting participation may improve over time.

Nocturnal Hypoglycemia in Patients With Diabetes Discharged From ICUs: A Prospective Two-Center Cohort Study.

OBJECTIVES: There is very limited information about glycemic control after discharge from the ICU. The aims of this study were to evaluate the prevalence of hypoglycemia in ICU survivors with type-2 diabetes and determine whether hypoglycemia is associated with cardiac arrhythmias. DESIGN: Prospective, observational, two-center study. Participants underwent up to 5 days of simultaneous blinded continuous interstitial glucose monitoring and ambulatory 12-lead electrocardiogram monitoring immediately after ICU discharge during ward-based care. Frequency of arrhythmias, heart rate variability, and cardiac repolarization markers were compared between hypoglycemia (interstitial glucose ≤ 3.5 mmol/L) and euglycemia (5-10 mmol/L) matched for time of day. SETTING: Mixed medical-surgical ICUs in two geographically distinct university-affiliated hospitals. PATIENTS: Patients with type-2 diabetes who were discharged from ICU after greater than or equal to 24 hours with greater than or equal to one organ failure and were prescribed subcutaneous insulin were eligible. MEASUREMENTS AND MAIN RESULTS: Thirty-one participants (mean ± sd, age 65 ± 13 yr, glycated hemoglobin 64 ± 22 mmol/mol) were monitored for 101 ± 32 hours post-ICU (total 3,117 hr). Hypoglycemia occurred in 12 participants (39%; 95% CI, 22-56%) and was predominantly nocturnal (40/51 hr) and asymptomatic (25/29 episodes). Participants experiencing hypoglycemia had 2.4 ± 0.7 discrete episodes lasting 45 minutes (interquartile range, 25-140 min). Glucose nadir was less than or equal to 2.2 mmol/L in 34% of episodes. The longest episode of nocturnal hypoglycemia was 585 minutes with glucose nadir less than 2.2 mmol/L. Simultaneous electrocardiogram and continuous interstitial glucose monitoring recordings were obtained during 44 hours of hypoglycemia and 991 hours of euglycemia. Hypoglycemia was associated with greater risk of bradycardia but did not affect atrial or ventricular ectopics, heart rate variability, or cardiac repolarization. CONCLUSIONS: In ICU survivors with insulin-treated type-2 diabetes, hypoglycemia occurs frequently and is predominantly nocturnal, asymptomatic, and prolonged.

Protein absorption and kinetics in critical illness.

PURPOSE OF REVIEW: Timing, dose, and route of protein feeding in critically ill patients treated in an ICU is controversial. This is because of conflicting outcomes observed in randomized controlled trials (RCTs). This inconsistency between RCTs may occur as the physiology of protein metabolism and protein handling in the critically ill is substantially different from the healthy with limited mechanistic data to inform design of RCTs. This review will outline the current knowledge and gaps in the understanding of protein absorption and kinetics during critical illness. RECENT FINDINGS: Critically ill patients, both children and adults, lose muscle protein because of substantial increases in protein degradation with initially normal, and over time increasing, protein synthesis rates. Critically ill patients appear to retain the capacity to absorb dietary protein and to use it for building body protein; however, the extent and possible benefit of this needs to be elucidated. More sophisticated methods to study protein absorption and digestion have recently been described but these have yet to be used in the critically ill. SUMMARY: Adequate understanding of protein absorption and kinetics during critical illness will help the design of better interventional studies in the future. Because of the complexity of measuring protein absorption and kinetics in the critically ill, very few investigations are executed. Recent data using isotope-labelled amino acids suggests that critically ill patients are able to absorb enteral protein and to synthesize new body protein. However, the magnitude of absorption and anabolism that occurs, and possible benefits for the patients need to be elucidated.

Incidence and management of metabolic acidosis with sodium bicarbonate in the ICU: An international observational study.

BACKGROUND: Metabolic acidosis is a major complication of critical illness. However, its current epidemiology and its treatment with sodium bicarbonate given to correct metabolic acidosis in the ICU are poorly understood. METHOD: This was an international retrospective observational study in 18 ICUs in Australia, Japan, and Taiwan. Adult patients were consecutively screened, and those with early metabolic acidosis (pH < 7.3 and a Base Excess < -4 mEq/L, within 24-h of ICU admission) were included. Screening continued until 10 patients who received and 10 patients who did not receive sodium bicarbonate in the first 24 h (early bicarbonate therapy) were included at each site. The primary outcome was ICU mortality, and the association between sodium bicarbonate and the clinical outcomes were assessed using regression analysis with generalized linear mixed model. RESULTS: We screened 9437 patients. Of these, 1292 had early metabolic acidosis (14.0%). Early sodium bicarbonate was given to 18.0% (233/1292) of these patients. Dosing, physiological, and clinical outcome data were assessed in 360 patients. The median dose of sodium bicarbonate in the first 24 h was 110 mmol, which was not correlated with bodyweight or the severity of metabolic acidosis. Patients who received early sodium bicarbonate had higher APACHE III scores, lower pH, lower base excess, lower PaCO2, and a higher lactate and received higher doses of vasopressors. After adjusting for confounders, the early administration of sodium bicarbonate was associated with an adjusted odds ratio (aOR) of 0.85 (95% CI, 0.44 to 1.62) for ICU mortality. In patients with vasopressor dependency, early sodium bicarbonate was associated with higher mean arterial pressure at 6 h and an aOR of 0.52 (95% CI, 0.22 to 1.19) for ICU mortality. CONCLUSIONS: Early metabolic acidosis is common in critically ill patients. Early sodium bicarbonate is administered by clinicians to more severely ill patients but without correction for weight or acidosis severity. Bicarbonate therapy in acidotic vasopressor-dependent patients may be beneficial and warrants further investigation.

Expert consensus statements for the management of COVID-19-related acute respiratory failure using a Delphi method.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare system globally. Lack of high-quality evidence on the respiratory management of COVID-19-related acute respiratory failure (C-ARF) has resulted in wide variation in clinical practice. METHODS: Using a Delphi process, an international panel of 39 experts developed clinical practice statements on the respiratory management of C-ARF in areas where evidence is absent or limited. Agreement was defined as achieved when > 70% experts voted for a given option on the Likert scale statement or > 80% voted for a particular option in multiple-choice questions. Stability was assessed between the two concluding rounds for each statement, using the non-parametric Chi-square (χ2) test (p < 0·05 was considered as unstable). RESULTS: Agreement was achieved for 27 (73%) management strategies which were then used to develop expert clinical practice statements. Experts agreed that COVID-19-related acute respiratory distress syndrome (ARDS) is clinically similar to other forms of ARDS. The Delphi process yielded strong suggestions for use of systemic corticosteroids for critical COVID-19; awake self-proning to improve oxygenation and high flow nasal oxygen to potentially reduce tracheal intubation; non-invasive ventilation for patients with mixed hypoxemic-hypercapnic respiratory failure; tracheal intubation for poor mentation, hemodynamic instability or severe hypoxemia; closed suction systems; lung protective ventilation; prone ventilation (for 16-24 h per day) to improve oxygenation; neuromuscular blocking agents for patient-ventilator dyssynchrony; avoiding delay in extubation for the risk of reintubation; and similar timing of tracheostomy as in non-COVID-19 patients. There was no agreement on positive end expiratory pressure titration or the choice of personal protective equipment. CONCLUSION: Using a Delphi method, an agreement among experts was reached for 27 statements from which 20 expert clinical practice statements were derived on the respiratory management of C-ARF, addressing important decisions for patient management in areas where evidence is either absent or limited. TRIAL REGISTRATION: The study was registered with Clinical trials.gov Identifier: NCT04534569.