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.

Reversal of cerebral ischaemia and hypoxia and of sickness behaviour by megadose sodium ascorbate in ovine Gram-negative sepsis.

BACKGROUND: The mechanisms by which megadose sodium ascorbate improves clinical status in experimental sepsis is unclear. We determined its effects on cerebral perfusion, oxygenation, and temperature, and plasma levels of inflammatory biomarkers, nitrates, nitrites, and ascorbate in ovine Gram-negative sepsis. METHODS: Sepsis was induced by i.v. infusion of live Escherichia coli for 31 h in unanaesthetised Merino ewes instrumented with a combination sensor in the frontal cerebral cortex to measure tissue perfusion, oxygenation, and temperature. Fluid resuscitation at 23 h was followed by i.v. megadose sodium ascorbate (0.5 g kg-1 over 30 min+0.5 g kg-1 h-1 for 6.5 h) or vehicle (n=6 per group). Norepinephrine was titrated to restore mean arterial pressure (MAP) to 70-80 mm Hg. RESULTS: At 23 h of sepsis, MAP (mean [sem]: 85 [2] to 64 [2] mm Hg) and plasma ascorbate (27 [2] to 15 [1] µM) decreased (both P<0.001). Cerebral ischaemia (901 [58] to 396 [40] units), hypoxia (34 [1] to 19 [3] mm Hg), and hyperthermia (39.5 [0.1]°C to 40.8 [0.1]°C) (all P<0.001) developed, accompanied by malaise and lethargy. Sodium ascorbate restored cerebral perfusion (703 [121] units], oxygenation (30 [2] mm Hg), temperature (39.2 [0.1]°C) (all PTreatment<0.05), and the behavioural state to normal. Sodium ascorbate slightly reduced the sepsis-induced increase in interleukin-6, returned VEGF-A to normal (both PGroupxTime<0.01), and increased plasma ascorbate (20 000 [300] µM; PGroup<0.001). The effects of sodium ascorbate were not reproduced by equimolar sodium bicarbonate. CONCLUSIONS: Megadose sodium ascorbate rapidly reversed sepsis-induced cerebral ischaemia, hypoxia, hyperthermia, and sickness behaviour. These effects were not reproduced by an equimolar sodium load.

Sex Differences in Opioid Administration After Cardiac Surgery.

OBJECTIVES: To assess whether there are sex-based differences in the administration of opioid analgesic drugs among inpatients after cardiac surgery. DESIGN: A retrospective cohort study. SETTING: At a tertiary academic referral center. PARTICIPANTS: Adult patients who underwent cardiac surgery from 2014 to 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the cumulative oral morphine equivalent dose (OMED) for the postoperative admission. Secondary outcomes were the daily difference in OMED and the administration of nonopioid analgesics. The authors developed multivariate regression models controlling for known confounders, including weight and length of stay. A total of 3,822 patients (1,032 women and 2,790 men) were included. The mean cumulative OMED was 139 mg for women and 180 mg for men, and this difference remained significant after adjustment for confounders (adjusted mean difference [aMD], -33.21 mg; 95% CI, -47.05 to -19.36 mg; p < 0.001). The cumulative OMED was significantly lower in female patients on postoperative days 1 to 5, with the greatest disparity observed on day 5 (aMD, -89.83 mg; 95% CI, -155.9 to -23.80 mg; p = 0.009). By contrast, women were more likely to receive a gabapentinoid (odds ratio, 1.91; 95% CI, 1.42-2.58; p < 0.001). The authors found no association between patient sex and the administration of other nonopioid analgesics or specific types of opioid analgesics. The authors found no association between patient sex and pain scores recorded within the first 48 hours after extubation, or the number of opioids administered in close proximity to pain assessments. CONCLUSIONS: Female sex was associated with significantly lower amounts of opioids administered after cardiac surgery.

Cerebral Glucose Metabolism following TBI: Changes in Plasma Glucose, Glucose Transport and Alternative Pathways of Glycolysis-A Translational Narrative Review.

Traumatic brain injury (TBI) is a major public health concern with significant consequences across various domains. Following the primary event, secondary injuries compound the outcome after TBI, with disrupted glucose metabolism emerging as a relevant factor. This narrative review summarises the existing literature on post-TBI alterations in glucose metabolism. After TBI, the brain undergoes dynamic changes in brain glucose transport, including alterations in glucose transporters and kinetics, and disruptions in the blood-brain barrier (BBB). In addition, cerebral glucose metabolism transitions from a phase of hyperglycolysis to hypometabolism, with upregulation of alternative pathways of glycolysis. Future research should further explore optimal, and possibly personalised, glycaemic control targets in TBI patients, with GLP-1 analogues as promising therapeutic candidates. Furthermore, a more fundamental understanding of alterations in the activation of various pathways, such as the polyol and lactate pathway, could hold the key to improving outcomes following TBI.

Nutrition practices in critically ill adults receiving noninvasive ventilation: A quantitative survey of Australian and New Zealand intensive care clinicians.

BACKGROUND: Noninvasive ventilation (NIV) is frequently used in the intensive care unit (ICU), yet there is a paucity of evidence to guide nutrition management during this therapy. Understanding clinicians' views on nutrition practices during NIV will inform research to address this knowledge gap. OBJECTIVE: The objective of this study was to describe Australian and New Zealand clinicians' views and perceptions of nutrition management during NIV in critically ill adults. METHODS: A cross-sectional quantitative online survey of Australian and New Zealand medical and nursing staff with ≥12 months ICU experience was disseminated through professional organisations via purposive snowball sampling from 29 August to 9 October 2022. Data collection included demographics, current practices, and views and perceptions of nutrition during NIV. Surveys <50% complete were excluded. Data are represented in number (%). RESULTS: A total of 152 surveys were analysed; 71 (47%) nursing, 69 (45%) medical, and 12 (8%) not specified. There was limited consensus on nutrition management during NIV; however, most clinicians (n = 108, 79%) reported that nutrition during NIV was 'important or very important'. Oral intake was perceived to be the most common route (n = 83, 55%), and 29 (21%) respondents viewed this as the safest. Most respondents (n = 106, 78%) reported that ≤50% of energy targets were met, with gastric enteral nutrition considered most likely to meet targets (n = 55, 40%). Reported nutrition barriers were aspiration risk (n = 87, 64%), fasting for intubation (n = 84, 62%), and nutrition perceived as a lower priority (n = 73, 54%). Reported facilitators were evidence-based guidelines (n = 77, 57%) and an NIV interface compatible with enteral nutrition tube (n = 77, 57%). CONCLUSION: ICU medical and nursing staff reported nutrition during NIV to be important; however, there was a lack of consensus on the route of feeding considered to be the safest and most likely to achieve nutrition targets. Interventions to minimise aspiration and fasting, including an interface with nasoenteric tube compatibility, should be explored.

Postprandial plasma GLP-1 levels are elevated in individuals with postprandial hypoglycaemia following Roux-en-Y gastric bypass - a systematic review.

BACKGROUND AND AIMS: Bariatric surgery is the most effective treatment in individuals with obesity to achieve remission of type 2 diabetes. Post-bariatric surgery hypoglycaemia occurs frequently, and management remains suboptimal, because of a poor understanding of the underlying pathophysiology. The glucoregulatory hormone responses to nutrients in individuals with and without post-bariatric surgery hypoglycaemia have not been systematically examined. MATERIALS AND METHODS: The study protocol was prospectively registered with PROSPERO. PubMed, EMBASE, Web of Science and the Cochrane databases were searched for publications between January 1990 and November 2021 using MeSH terms related to post-bariatric surgery hypoglycaemia. Studies were included if they evaluated individuals with post-bariatric surgery hypoglycaemia and included measurements of plasma glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), insulin, C-peptide and/or glucagon concentrations following an ingested nutrient load. Glycated haemoglobin (HbA1c) was also evaluated. A random-effects meta-analysis was performed, and Hedges' g (standardised mean difference) and 95% confidence intervals were reported for all outcomes where sufficient studies were available. The τ2 estimate and I2 statistic were used as tests for heterogeneity and a funnel plot with the Egger regression-based test was used to evaluate for publication bias. RESULTS: From 377 identified publications, 12 were included in the analysis. In all 12 studies, the type of bariatric surgery was Roux-en-Y gastric bypass (RYGB). Comparing individuals with and without post-bariatric surgery hypoglycaemia following an ingested nutrient load, the standardised mean difference in peak GLP-1 was 0.57 (95% CI, 0.32, 0.82), peak GIP 0.05 (-0.26, 0.36), peak insulin 0.84 (0.44, 1.23), peak C-peptide 0.69 (0.28, 1.1) and peak glucagon 0.05 (-0.26, 0.36). HbA1c was less in individuals with hypoglycaemia - 0.40 (-0.67, -0.12). There was no evidence of substantial heterogeneity in any outcome except for peak insulin: τ2 = 0.2, I2 = 54.3. No publication bias was evident. CONCLUSION: Following RYGB, postprandial peak plasma GLP-1, insulin and C-peptide concentrations are greater in individuals with post-bariatric surgery hypoglycaemia, while HbA1c is less. These observations support the concept that antagonism of GLP-1 would prove beneficial in the management of individuals with hypoglycaemia following RYGB.PROSPERO Registration Number: CRD42021287515.

Mega-dose sodium ascorbate: a pilot, single-dose, physiological effect, double-blind, randomized, controlled trial.

BACKGROUND: Mega-dose sodium ascorbate (NaAscorbate) appears beneficial in experimental sepsis. However, its physiological effects in patients with septic shock are unknown. METHODS: We conducted a pilot, single-dose, double-blind, randomized controlled trial. We enrolled patients with septic shock within 24 h of diagnosis. We randomly assigned them to receive a single mega-dose of NaAscorbate (30 g over 1 h followed by 30 g over 5 h) or placebo (vehicle). The primary outcome was the total 24 h urine output (UO) from the beginning of the study treatment. Secondary outcomes included the time course of the progressive cumulative UO, vasopressor dose, and sequential organ failure assessment (SOFA) score. RESULTS: We enrolled 30 patients (15 patients in each arm). The mean (95% confidence interval) total 24-h UO was 2056 (1520-2593) ml with placebo and 2948 (2181-3715) ml with NaAscorbate (mean difference 891.5, 95% confidence interval [- 2.1 to 1785.2], P = 0.051). Moreover, the progressive cumulative UO was greater over time on linear mixed modelling with NaAscorbate (P < 0.001). Vasopressor dose and SOFA score changes over time showed faster reductions with NaAscorbate (P < 0.001 and P = 0.042). The sodium level, however, increased more over time with NaAscorbate (P < 0.001). There was no statistical difference in other clinical outcomes. CONCLUSION: In patients with septic shock, mega-dose NaAscorbate did not significantly increase cumulative 24-h UO. However, it induced a significantly greater increase in UO and a greater reduction in vasopressor dose and SOFA score over time. One episode of hypernatremia and one of hemolysis were observed in the NaAscorbate group. These findings support further cautious investigation of this novel intervention. Trial registration Australian New Zealand Clinical Trial Registry (ACTRN12620000651987), Date registered June/5/2020.

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.

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.

Dynamic Heterogeneity Shapes Patterns of Spiral Ganglion Activity.

Neural response properties that typify primary sensory afferents are critical to fully appreciate because they establish and, ultimately represent, the fundamental coding design used for higher-level processing. Studies illuminating the center-surround receptive fields of retinal ganglion cells, for example, were ground-breaking because they determined the foundation of visual form detection. For the auditory system, a basic organizing principle of the spiral ganglion afferents is their extensive electrophysiological heterogeneity establishing diverse intrinsic firing properties in neurons throughout the spiral ganglion. Moreover, these neurons display an impressively large array of neurotransmitter receptor types that are responsive to efferent feedback. Thus, electrophysiological diversity and its neuromodulation are a fundamental encoding mechanism contributed by the primary afferents in the auditory system. To place these features into context, we evaluated the effects of hyperpolarization and cAMP on threshold level as indicators of overall afferent responsiveness in CBA/CaJ mice of either sex. Hyperpolarization modified threshold gradients such that distinct voltage protocols could shift the relationship between sensitivity and stimulus input to reshape resolution. This resulted in an "accordion effect" that appeared to stretch, compress, or maintain responsivity across the gradient of afferent thresholds. cAMP targeted threshold and kinetic shifts to rapidly adapting neurons, thus revealing multiple cochleotopic properties that could potentially be independently regulated. These examples of dynamic heterogeneity in primary auditory afferents not only have the capacity to shift the range, sensitivity, and resolution, but to do so in a coordinated manner that appears to orchestrate changes with a seemingly unlimited repertoire.SIGNIFICANCE STATEMENT How do we discriminate the more nuanced qualities of the sound around us? Beyond the basics of pitch and loudness, aspects, such as pattern, distance, velocity, and location, are all attributes that must be used to encode acoustic sensations effectively. While higher-level processing is required for perception, it would not be unexpected if the primary auditory afferents optimized receptor input to expedite neural encoding. The findings reported herein are consistent with this design. Neuromodulation compressed, expanded, shifted, or realigned intrinsic electrophysiological heterogeneity to alter neuronal responses selectively and dynamically. This suggests that diverse spiral ganglion phenotypes provide a rich substrate to support an almost limitless array of coding strategies within the first neural element of the auditory pathway.

Amplification of input differences by dynamic heterogeneity in the spiral ganglion.

A defining feature of type I primary auditory afferents that compose ∼95% of the spiral ganglion is their intrinsic electrophysiological heterogeneity. This diversity is evident both between and within unitary, rapid, and slow adaptation (UA, RA, and SA) classes indicative of specializations designed to shape sensory receptor input. But to what end? Our initial impulse is to expect the opposite: that auditory afferents fire uniformly to represent acoustic stimuli with accuracy and high fidelity. Yet this is clearly not the case. One explanation for this neural signaling strategy is to coordinate a system in which differences between input stimuli are amplified. If this is correct, then stimulus disparity enhancements within the primary afferents should be transmitted seamlessly into auditory processing pathways that utilize population coding for difference detection. Using sound localization as an example, one would expect to observe separately regulated differences in intensity level compared with timing or spectral cues within a graded tonotopic distribution. This possibility was evaluated by examining the neuromodulatory effects of cAMP on immature neurons with high excitability and slow membrane kinetics. We found that electrophysiological correlates of intensity and timing were indeed independently regulated and tonotopically distributed, depending on intracellular cAMP signaling level. These observations, therefore, are indicative of a system in which differences between signaling elements of individual stimulus attributes are systematically amplified according to auditory processing constraints. Thus, dynamic heterogeneity mediated by cAMP in the spiral ganglion has the potential to enhance the representations of stimulus input disparities transmitted into higher level difference detection circuitry.NEW & NOTEWORTHY Can changes in intracellular second messenger signaling within primary auditory afferents shift our perception of sound? Results presented herein lead to this conclusion. We found that intracellular cAMP signaling level systematically altered the kinetics and excitability of primary auditory afferents, exemplifying how dynamic heterogeneity can enhance differences between electrophysiological correlates of timing and intensity.

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.

Elevated Cardiac Troponin to Detect Acute Cellular Rejection After Cardiac Transplantation: A Systematic Review and Meta-Analysis.

Cardiac troponin is well known as a highly specific marker of cardiomyocyte damage, and has significant diagnostic accuracy in many cardiac conditions. However, the value of elevated recipient troponin in diagnosing adverse outcomes in heart transplant recipients is uncertain. We searched MEDLINE (Ovid), Embase (Ovid), and the Cochrane Library from inception until December 2020. We generated summary sensitivity, specificity, and Bayesian areas under the curve (BAUC) using bivariate Bayesian modelling, and standardised mean differences (SMDs) to quantify the diagnostic relationship of recipient troponin and adverse outcomes following cardiac transplant. We included 27 studies with 1,684 cardiac transplant recipients. Patients with acute rejection had a statistically significant late elevation in standardised troponin measurements taken at least 1 month postoperatively (SMD 0.98, 95% CI 0.33-1.64). However, pooled diagnostic accuracy was poor (sensitivity 0.414, 95% CrI 0.174-0.696; specificity 0.785, 95% CrI 0.567-0.912; BAUC 0.607, 95% CrI 0.469-0.723). In summary, late troponin elevation in heart transplant recipients is associated with acute cellular rejection in adults, but its stand-alone diagnostic accuracy is poor. Further research is needed to assess its performance in predictive modelling of adverse outcomes following cardiac transplant. Systematic Review Registration: identifier CRD42021227861.

People in intensive care with COVID-19: demographic and clinical features during the first, second, and third pandemic waves in Australia.

OBJECTIVE: To compare the demographic and clinical features, management, and outcomes for patients admitted with COVID-19 to intensive care units (ICUs) during the first, second, and third waves of the pandemic in Australia. DESIGN, SETTING, AND PARTICIPANTS: People aged 16 years or more admitted with polymerase chain reaction-confirmed COVID-19 to the 78 Australian ICUs participating in the Short Period Incidence Study of Severe Acute Respiratory Infection (SPRINT-SARI) Australia project during the first (27 February - 30 June 2020), second (1 July 2020 - 25 June 2021), and third COVID-19 waves (26 June - 1 November 2021). MAIN OUTCOME MEASURES: Primary outcome: in-hospital mortality. SECONDARY OUTCOMES: ICU mortality; ICU and hospital lengths of stay; supportive and disease-specific therapies. RESULTS: 2493 people (1535 men, 62%) were admitted to 59 ICUs: 214 during the first (9%), 296 during the second (12%), and 1983 during the third wave (80%). The median age was 64 (IQR, 54-72) years during the first wave, 58 (IQR, 49-68) years during the second, and 54 (IQR, 41-65) years during the third. The proportion without co-existing illnesses was largest during the third wave (41%; first wave, 32%; second wave, 29%). The proportion of ICU beds occupied by patients with COVID-19 was 2.8% (95% CI, 2.7-2.9%) during the first, 4.6% (95% CI, 4.3-5.1%) during the second, and 19.1% (95% CI, 17.9-20.2%) during the third wave. Non-invasive (42% v 15%) and prone ventilation strategies (63% v 15%) were used more frequently during the third wave than during the first two waves. Thirty patients (14%) died in hospital during the first wave, 35 (12%) during the second, and 281 (17%) during the third. After adjusting for age, illness severity, and other covariates, the risk of in-hospital mortality was similar for the first and second waves, but 9.60 (95% CI, 3.52-16.7) percentage points higher during the third than the first wave. CONCLUSION: The demographic characteristics of patients in intensive care with COVID-19 and the treatments they received during the third pandemic wave differed from those of the first two waves. Adjusted in-hospital mortality was highest during the third wave.

Epidemiology of persistent postoperative opioid use after cardiac surgery: a systematic review and meta-analysis.

BACKGROUND: The epidemiology of persistent postoperative opioid use at least 3 months after cardiac surgery is poorly characterised despite its potential public health importance. METHODS: We searched MEDLINE, Embase, and Google Scholar from inception to December 2021 and included studies reporting the rate and risk factors of persistent postoperative opioid use after cardiac surgery in opioid-naive and opioid-exposed patients. We recorded incidence rates and odds ratios (ORs) with 95% confidence intervals (CIs) for risk factors from individual studies and used random-effects inverse variance modelling to generate pooled estimates. RESULTS: From 10 studies involving 112 298 patients, the pooled rate of persistent postoperative opioid use in opioid-naive patients was 5.7% (95% CI: 4.2-7.2%). Risk factors included female sex (OR 1.18; 95% CI: 1.09-1.29), smoking (OR 1.34; 95% CI: 1.06-1.69), alcohol use (OR 1.43; 95% CI: 1.17-1.76), congestive cardiac failure (OR 1.17; 95% CI: 1.08-1.27), diabetes mellitus (OR 1.21; 95% CI: 1.07-1.37), chronic lung disease (OR 1.42; 95% CI: 1.16-1.75), chronic kidney disease (OR 1.35; 95% CI: 1.08-1.68), and length of hospital stay (per day) (OR 1.03; 95% CI: 1.02-1.04). CONCLUSIONS: Persistent postoperative opioid use after cardiac surgery affects at least one in 20 patients. The identification of risk factors, such as female sex, smoking, alcohol use, congestive cardiac failure, diabetes mellitus, chronic lung disease, chronic kidney disease, and length of hospital stay, should help target interventions aimed at decreasing its prevalence.

Perioperative Neutrophil-Lymphocyte Ratio Predicts Mortality After Cardiac Surgery: Systematic Review and Meta-Analysis.

OBJECTIVES: Neutrophil-lymphocyte ratio (NLR) is an inflammatory biomarker that has been evaluated across a variety of surgical disciplines and is widely predictive of poor postoperative outcome, but its value in cardiac surgery is unclear. The authors did this systematic review and meta-analysis to determine the impact of elevated perioperative NLR on survival after cardiac surgery. DESIGN: Systematic review and meta-analysis of study-level data. SETTING: Multiple hospitals involved in an international pool of studies. PARTICIPANTS: Adults undergoing cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors searched multiple databases from inception until November 2020. They generated summary hazard ratios (HR) and odds ratios (OR) for the association of elevated preoperative NLR with long-term and short-term mortality following cardiac surgery. They separately reported on elevated postoperative NLR. Between-study heterogeneity was explored using metaregression. The authors included 12 studies involving 13,262 patients undergoing cardiac surgery. Elevated preoperative NLR was associated with worse long-term (>30 days) (hazard ratio [HR] 1.56; 95% CI [confidence interval], 1.18-2.06; 8 studies) and short-term (<30 days) mortality (OR 3.18; 95% CI, 1.90-5.30; 7 studies). One study reported the association of elevated postoperative NLR with long-term mortality (HR 8.58; 95% CI, 2.55-28.85). There was considerable between-study heterogeneity for the analysis of long-term mortality (I2 statistic 94.39%), which mostly was explained by study-level variables, such as the number of variables adjusted for by included studies and how many of these significantly increased the risk of long-term mortality, high risk of bias, and number of study centers, as well as participant level factors, such as average participant age and hypertension prevalence. CONCLUSIONS: Perioperative NLR is an independent predictor of short-term and long-term postoperative mortality following cardiac surgery. Further research is required to determine which patient-level factors modify the prognostic value of NLR and to evaluate its role in routine clinical practice.

Gut dysfunction in the ICU: diagnosis and management.

PURPOSE OF REVIEW: Progress has been made in our understanding of gut dysfunction in critical illness. This review will outline new findings and give perspectives based on previous knowledge and concurrent advances in nutrition. RECENT FINDINGS: The relationship between gut dysfunction and poor outcomes in critical illness has received considerable interest. It remains uncertain whether gut dysfunction is merely a marker of illness severity or if it is directly responsible for prolonged critical illness and increased mortality. This relationship is difficult to ascertain given there is no agreed method for identification and quantification; biomarkers such as intestinal fatty acid binding protein and citrulline show promise but require further study. Recent studies have investigated strategies to deliver enteral nutrition targets with impacts on gut function, including high calorie or protein formulae, intermittent regimes and novel prokinetics. SUMMARY: Gut dysfunction is associated with poor outcomes, but it remains uncertain whether strategies to improve gut function will influence survival and recovery.

Outcomes for patients with COVID-19 admitted to Australian intensive care units during the first four months of the pandemic.

OBJECTIVES: To describe the characteristics and outcomes of patients with COVID-19 admitted to intensive care units (ICUs) during the initial months of the pandemic in Australia. DESIGN, SETTING: Prospective, observational cohort study in 77 ICUs across Australia. PARTICIPANTS: Patients admitted to participating ICUs with laboratory-confirmed COVID-19 during 27 February - 30 June 2020. MAIN OUTCOME MEASURES: ICU mortality and resource use (ICU length of stay, peak bed occupancy). RESULTS: The median age of the 204 patients with COVID-19 admitted to intensive care was 63.5 years (IQR, 53-72 years); 140 were men (69%). The most frequent comorbid conditions were obesity (40% of patients), diabetes (28%), hypertension treated with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (24%), and chronic cardiac disease (20%); 73 patients (36%) reported no comorbidity. The most frequent source of infection was overseas travel (114 patients, 56%). Median peak ICU bed occupancy was 14% (IQR, 9-16%). Invasive ventilation was provided for 119 patients (58%). Median length of ICU stay was greater for invasively ventilated patients than for non-ventilated patients (16 days; IQR, 9-28 days v 3 days; IQR, 2-5 days), as was ICU mortality (26 deaths, 22%; 95% CI, 15-31% v four deaths, 5%; 95% CI, 1-12%). Higher Acute Physiology and Chronic Health Evaluation II (APACHE-II) scores on ICU day 1 (adjusted hazard ratio [aHR], 1.15; 95% CI, 1.09-1.21) and chronic cardiac disease (aHR, 3.38; 95% CI, 1.46-7.83) were each associated with higher ICU mortality. CONCLUSION: Until the end of June 2020, mortality among patients with COVID-19 who required invasive ventilation in Australian ICUs was lower and their ICU stay longer than reported overseas. Our findings highlight the importance of ensuring adequate local ICU capacity, particularly as the pandemic has not yet ended.

Considering intervention intensity in habitat restoration planning: An application to Pacific salmon.

Habitat restoration is a key strategy for recovering imperiled species, and planning habitat restoration activities cost effectively can help advance recovery objectives. Habitat restoration planning involves decisions about where and when to undertake restoration, and what type of restoration to undertake. This article focuses on decisions about the amount of restoration to undertake for a given type, location, and time, termed intervention intensity. A return on investment framework is developed for incorporating intervention intensity into habitat restoration planning. The framework is then applied in the context of planning habitat restoration for Pacific salmon recovery as a case study. Results showed that no single intervention type or location dominated, and several returns to scale relationships emerged across the candidate interventions. Scenarios that considered interventions across multiple intensities outperformed single-intensity scenarios in terms of total benefits and cost effectiveness. These findings highlight the usefulness of exploratory return on investment analysis for prioritizing habitat restoration interventions, and underscore the importance of systematically considering how much restoration to undertake, in addition to what to do and where.