Quantifying the Impact of Alternative Definitions of Sepsis-Associated Acute Kidney Injury on its Incidence and Outcomes: A Systematic Review and Meta-Analysis.

OBJECTIVES: To derive a pooled estimate of the incidence and outcomes of sepsis-associated acute kidney injury (SA-AKI) in ICU patients and to explore the impact of differing definitions of SA-AKI on these estimates. DATA SOURCES: Medline, Medline Epub, EMBASE, and Cochrane CENTRAL between 1990 and 2023. STUDY SELECTION: Randomized clinical trials and prospective cohort studies of adults admitted to the ICU with either sepsis and/or SA-AKI. DATA EXTRACTION: Data were extracted in duplicate. Risk of bias was assessed using adapted standard tools. Data were pooled using a random-effects model. Heterogeneity was assessed by using a single covariate logistic regression model. The primary outcome was the proportion of participants in ICU with sepsis who developed AKI. DATA SYNTHESIS: A total of 189 studies met inclusion criteria. One hundred fifty-four reported an incidence of SA-AKI, including 150,978 participants. The pooled proportion of patients who developed SA-AKI across all definitions was 0.40 (95% CI, 0.37-0.42) and 0.52 (95% CI, 0.48-0.56) when only the Risk Injury Failure Loss End-Stage, Acute Kidney Injury Network, and Improving Global Outcomes definitions were used to define SA-AKI. There was significant variation in the incidence of SA-AKI depending on the definition of AKI used and whether AKI defined by urine output criteria was included; the incidence was lowest when receipt of renal replacement therapy was used to define AKI (0.26; 95% CI, 0.24-0.28), and highest when the Acute Kidney Injury Network score was used (0.57; 95% CI, 0.45-0.69; p < 0.01). Sixty-seven studies including 29,455 participants reported at least one SA-AKI outcome. At final follow-up, the proportion of patients with SA-AKI who had died was 0.48 (95% CI, 0.43-0.53), and the proportion of surviving patients who remained on dialysis was 0.10 (95% CI, 0.04-0.17). CONCLUSIONS: SA-AKI is common in ICU patients with sepsis and carries a high risk of death and persisting kidney impairment. The incidence and outcomes of SA-AKI vary significantly depending on the definition of AKI used.

Effect of level of sedation on outcomes in critically ill adult patients: a systematic review of clinical trials with meta-analysis and trial sequential analysis.

Background: Sedation is routinely administered to critically ill patients to alleviate anxiety, discomfort, and patient-ventilator asynchrony. However, it must be balanced against risks such as delirium and prolonged intensive care stays. This study aimed to investigate the effects of different levels of sedation in critically ill adults. Methods: Systematic review with meta-analysis and trial sequential analysis (TSA) of randomised clinical trials including critically ill adults admitted to the intensive care unit. CENTRAL, MEDLINE, Embase, LILACS, and Web of Science were searched from their inception to 13 June 2023. Risks of bias were assessed using the Cochrane risk of bias tool. Primary outcome was all-cause mortality. Aggregate data were synthesised with meta-analyses and TSA, and the certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. This study is registered with PROSPERO: CRD42023386960. Findings: Fifteen trials randomising 4352 patients were included, of which 13 were assessed high risk of bias. Meta-analyses comparing lighter to deeper sedation showed no evidence of a difference in all-cause mortality (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.83-1.06; p = 0.28; 15 trials; moderate certainty evidence), serious adverse events (RR 0.99, CI 0.92-1.06; p = 0.80; 15 trials; moderate certainty evidence), or delirium (RR 1.01, 95% CI 0.94-1.09; p = 0.78; 11 trials; moderate certainty evidence). TSA showed that when assessing mortality, a relative risk reduction of 16% or more between the compared interventions could be rejected. Interpretation: The level of sedation has not been shown to affect the risks of death, delirium, and other serious adverse events in critically ill adult patients. While TSA suggests that additional trials are unlikely to significantly change the conclusion of the meta-analyses, the certainty of evidence was moderate. This suggests a need for future high-quality studies with higher methodological rigor. Funding: None.

PRECISION-TBI: a study protocol for a vanguard prospective cohort study to enhance understanding and management of moderate to severe traumatic brain injury in Australia.

INTRODUCTION: Traumatic brain injury (TBI) is a heterogeneous condition in terms of pathophysiology and clinical course. Outcomes from moderate to severe TBI (msTBI) remain poor despite concerted research efforts. The heterogeneity of clinical management represents a barrier to progress in this area. PRECISION-TBI is a prospective, observational, cohort study that will establish a clinical research network across major neurotrauma centres in Australia. This network will enable the ongoing collection of injury and clinical management data from patients with msTBI, to quantify variations in processes of care between sites. It will also pilot high-frequency data collection and analysis techniques, novel clinical interventions, and comparative effectiveness methodology. METHODS AND ANALYSIS: PRECISION-TBI will initially enrol 300 patients with msTBI with Glasgow Coma Scale (GCS) <13 requiring intensive care unit (ICU) admission for invasive neuromonitoring from 10 Australian neurotrauma centres. Demographic data and process of care data (eg, prehospital, emergency and surgical intervention variables) will be collected. Clinical data will include prehospital and emergency department vital signs, and ICU physiological variables in the form of high frequency neuromonitoring data. ICU treatment data will also be collected for specific aspects of msTBI care. Six-month extended Glasgow Outcome Scores (GOSE) will be collected as the key outcome. Statistical analysis will focus on measures of between and within-site variation. Reports documenting performance on selected key quality indicators will be provided to participating sites. ETHICS AND DISSEMINATION: Ethics approval has been obtained from The Alfred Human Research Ethics Committee (Alfred Health, Melbourne, Australia). All eligible participants will be included in the study under a waiver of consent (hospital data collection) and opt-out (6 months follow-up). Brochures explaining the rationale of the study will be provided to all participants and/or an appropriate medical treatment decision-maker, who can act on the patient's behalf if they lack capacity. Study findings will be disseminated by peer-review publications. TRIAL REGISTRATION NUMBER: NCT05855252.

The effect of sugammadex on patient morbidity and quality of recovery after general anaesthesia: a systematic review and meta-analysis.

BACKGROUND: Residual neuromuscular block is associated with increased patient morbidity. Therefore prevention of residual neuromuscular block is an important component of general anaesthesia where neuromuscular blocking agents are used. Whereas sugammadex improves reversal based on neuromuscular twitch monitoring parameters, there have been no prospective, adequately powered definitive studies demonstrating that sugammadex is also associated with less patient morbidity. METHODS: We performed a systematic review of randomised trials comparing sugammadex with anticholinesterase-based reversal or placebo reversal that reported important patient outcomes beyond the postanaesthesia care unit. RESULTS: We identified 43 articles, including 5839 trial participants. Only one trial reported days alive and out of hospital to 30 days (DAOH-30), which showed that the number of DAOH-30 was similar in those allocated to sugammadex compared with neostigmine-based reversal (25 days [19-27] vs 24 days [21-27], median difference 0.00 [-2.15 to 2.15]). Pooled analyses of data from 16 trials showed an estimated odds ratio (OR) for postoperative pulmonary complications of 0.67 (95% confidence interval 0.47-0.95) with sugammadex use. Pooled analysis showed that pneumonia (eight trials OR 0.51 [0.24-1.01] with sugammadex use), hospital length of stay (23 trials, mean difference -0.31 [-0.84 to 0.22] with sugammadex use), and patient-reported quality of recovery (11 trials, varied depending on metric used) are similar in those allocated to sugammadex vs control. The difference seen in mortality (11 trials, OR 0.39 [0.15-1.01] with sugammadex use) would be considered to be clinically significant and warrants further investigation, however, the rarity of these events precludes drawing definitive conclusions. CONCLUSION: Although few trials reported on DAOH-30 or important patient outcomes, sugammadex is associated with a reduction in postoperative pulmonary complications, however, this might not translate to a difference in hospital length of stay, patient-reported quality of recovery, or mortality. CLINICAL TRIAL REGISTRATION: PROSPERO database (CRD42022325858).

Selective digestive tract decontamination in critically ill adults with acute brain injuries: a post hoc analysis of a randomized clinical trial.

PURPOSE: The aim of this study was to determine whether selective decontamination of the digestive tract (SDD) reduces in-hospital mortality in mechanically ventilated critically ill adults admitted to the intensive care unit (ICU) with acute brain injuries or conditions. METHODS: We carried out a post hoc analysis from a crossover, cluster randomized clinical trial. ICUs were randomly assigned to adopt or not to adopt a SDD strategy for two alternating 12-month periods, separated by a 3-month inter-period gap. Patients in the SDD group (n = 2791; 968 admitted to the ICU with an acute brain injury) received a 6-hourly application of an oral paste and administration of a gastric suspension containing colistin, tobramycin, and nystatin for the duration of mechanical ventilation, plus a 4-day course of an intravenous antibiotic with a suitable antimicrobial spectrum. Patients in the control group (n = 3191; 1093 admitted to the ICU with an acute brain injury) received standard care. The primary outcome was in-hospital mortality within 90 days. There were four secondary clinical outcomes: death in ICU, ventilator-, ICU- and hospital-free days to day 90. RESULTS: Of 2061 patients with acute brain injuries (mean age, 55.8 years; 36.4% women), all completed the trial. In patients with acute brain injuries, there were 313/968 (32.3%) and 415/1093 (38%) in-hospital deaths in the SDD and standard care groups (unadjusted odds ratio [OR], 0.76, 95% confidence interval [CI] 0.63-0.92; p = 0.004). The use of SDD was associated with statistically significant improvements in the four clinical secondary outcomes compared to standard care. There was no significant heterogeneity of treatment effect between patients with and without acute brain injuries (interaction p = 0.22). CONCLUSIONS: In this post hoc analysis of a randomized clinical trial in critically ill patients with acute brain injuries receiving mechanical ventilation, the use of SDD significantly reduced in-hospital mortality in patients compared to standard care without SDD. These findings require confirmation.

The feasibility and acceptability of a physician-led ICU follow-up service: A prospective cohort study.

BACKGROUND: Increased recognition of post-intensive care syndrome has led to widespread development of intensive care follow-up services internationally. OBJECTIVE: The objective of this study was to determine the feasibility and acceptability of an intensive care unit (ICU) follow-up clinic in Australia for patients and their caregivers and to describe satisfaction with this service. METHODS: This was a prospective cohort study in a mixed tertiary ICU in Australia. Eligible patients were adults admitted to the ICU for 7 days or more and/or ventilated for 48 h or more, as well as their primary caregiver. Patients and their primary caregivers were invited to attend a follow-up clinic 4-8 weeks after hospital discharge. The clinic appointment was attended by an ICU physician and nurse, with multidisciplinary support. Feasibility and acceptability were defined as the proportion of clinic attendance and frequency of interventions initiated at the clinic. Satisfaction was measured by a 5-point satisfaction survey (very dissatisfied to very satisfied). The burden of ongoing disease was reported via multiple validated instruments. RESULTS: From April 2020-July 2021, 386 patients met the inclusion criteria. Only 146 patients were approached for consent due to site staffing limitations. Eighty-three patients and 32 caregivers consented to attend the clinic. Seventy percent (54/77) of patients attended scheduled appointments and 50% (16/32) of caregivers. For patients, 23 medical referrals were made, 8 patients had medication changes, and 10 patients were offered social work support. Satisfaction surveys were completed by 65% (35/54) of attending patients; 97% (34) patients reported either being 'very satisfied' or 'satisfied' with the service. All responding caregivers (10) were either 'very satisfied' or 'satisfied' with the clinic. CONCLUSION: There were a large number of patients meeting the inclusion criteria to the ICU follow-up clinic, and clinic attendance was moderate for patients but lower for caregivers. Reported satisfaction with the service was high for both patients and their caregiver.

Fluid therapy in diabetic ketoacidosis.

PURPOSE OF REVIEW: To evaluate recent evidence (2021-2023) on fluid therapy in diabetic ketoacidosis. Key evidence gaps which require generation of new evidence are discussed. RECENT FINDINGS: Balanced crystalloid solutions, compared to the commonly recommended and used 0.9% sodium chloride solution (saline), may result in better outcomes for patients with diabetic ketoacidosis, including faster resolution of acidosis, less hyperchloremia and shorter hospital length of stay. Upcoming results from randomized trials may provide definitive evidence on the use of balanced crystalloid solutions in diabetic ketoacidosis. Evidence remains scarce or conflicting for the use of "two-bag" compared to conventional "one-bag" fluid, and rates of fluid administration, especially for adult patients. In children, concerns about cerebral oedema from faster fluid administration rates have not been demonstrated in cohort studies nor randomized trials. SUMMARY: Fluid therapy is a key aspect of diabetic ketoacidosis management, with important evidence gaps persisting for several aspects of management despite recent evidence.

Intensive glucose control in critically ill adults: a protocol for a systematic review and individual patient data meta-analysis / Controle intensivo da glicose em adultos em estado grave: um protocolo de revisão sistemática e metanálise de dados individuais de pacientes

ABSTRACT Objective: The optimal target for blood glucose concentration in critically ill patients is unclear. We will perform a systematic review and meta-analysis with aggregated and individual patient data from randomized controlled trials, comparing intensive glucose control with liberal glucose control in critically ill adults. Data sources: MEDLINE®, Embase, the Cochrane Central Register of Clinical Trials, and clinical trials registries (World Health Organization, clinical trials.gov). The authors of eligible trials will be invited to provide individual patient data. Published trial-level data from eligible trials that are not at high risk of bias will be included in an aggregated data meta-analysis if individual patient data are not available. Methods: Inclusion criteria: randomized controlled trials that recruited adult patients, targeting a blood glucose of ≤ 120mg/dL (≤ 6.6mmol/L) compared to a higher blood glucose concentration target using intravenous insulin in both groups. Excluded studies: those with an upper limit blood glucose target in the intervention group of > 120mg/dL (> 6.6mmol/L), or where intensive glucose control was only performed in the intraoperative period, and those where loss to follow-up exceeded 10% by hospital discharge. Primary endpoint: In-hospital mortality during index hospital admission. Secondary endpoints: mortality and survival at other timepoints, duration of invasive mechanical ventilation, vasoactive agents, and renal replacement therapy. A random effect Bayesian meta-analysis and hierarchical Bayesian models for individual patient data will be used. Discussion: This systematic review with aggregate and individual patient data will address the clinical question, 'what is the best blood glucose target for critically ill patients overall?' Protocol version 0.4 - 06/26/2023 PROSPERO registration: CRD42021278869

RESUMO Objetivo: Não está claro qual é a meta ideal de concentração de glicose no sangue em pacientes em estado grave. Realizaremos uma revisão sistemática e uma metanálise com dados agregados e de pacientes individuais de estudos controlados e randomizados, comparando o controle intensivo da glicose com o controle liberal da glicose em adultos em estado grave. Fontes de dados: MEDLINE®, Embase, Cochrane Central Register of Clinical Trials e registros de ensaios clínicos (Organização Mundial da Saúde, clinical trials.gov). Os autores dos estudos qualificados serão convidados a fornecer dados individuais de pacientes. Os dados publicados em nível de ensaio qualificado que não apresentem alto risco de viés serão incluídos em uma metanálise de dados agregados se os dados individuais de pacientes não estiverem disponíveis. Métodos: Critérios de inclusão: ensaios clínicos controlados e randomizados que recrutaram pacientes adultos, com meta de glicemia ≤ 120mg/dL (≤ 6,6mmol/L) comparada a uma meta de concentração de glicemia mais alta com insulina intravenosa em ambos os grupos. Estudos excluídos: aqueles com meta de glicemia no limite superior no grupo de intervenção > 120mg/dL (> 6,6mmol/L), ou em que o controle intensivo de glicose foi realizado apenas no período intraoperatório, e aqueles em que a perda de seguimento excedeu 10% até a alta hospitalar. Desfecho primário: Mortalidade intra-hospitalar durante a admissão hospitalar. Desfechos secundários: Mortalidade e sobrevida em outros momentos, duração da ventilação mecânica invasiva, agentes vasoativos e terapia de substituição renal. Utilizaremos metanálise bayesiana de efeito randômico e modelos bayesianos hierárquicos para dados individuais de pacientes. Discussão: Essa revisão sistemática com dados agregados e de pacientes individuais abordará a questão clínica: Qual é a melhor meta de glicose no sangue de pacientes graves em geral? Protocolo versão 0.4 - 26/06/2023 Registro PROSPERO: CRD42021278869

Sepsis-coded hospitalisations and associated costs in Australia: a retrospective analysis.

OBJECTIVE: To report trends in Australian hospitalisations coded for sepsis and their associated costs. DESIGN: Retrospective analysis of Australian national hospitalisation data from 2002 to 2021. METHODS: Sepsis-coded hospitalisations were identified using the Global Burden of Disease study sepsis-specific ICD-10 codes modified for Australia. Costs were calculated using Australian-Refined Diagnosis Related Group codes and National Hospital Cost Data Collection. RESULTS: Sepsis-coded hospitalisations increased from 36,628 in 2002-03 to 131,826 in 2020-21, an annual rate of 7.8%. Principal admission diagnosis codes contributed 13,843 (37.8%) in 2002-03 and 44,186 (33.5%) in 2020-21; secondary diagnosis codes contributed 22,785 (62.2%) in 2002-03 and 87,640 (66.5%) in 2020-21. Unspecified sepsis was the most common sepsis code, increasing from 15,178 hospitalisations in 2002-03 to 68,910 in 2020-21. The population-based incidence of sepsis-coded hospitalisations increased from 18.6 to 10,000 population (2002-03) to 51.3 per 10,000 (2021-21); representing an increase from 55.1 to 10,000 hospitalisations in 2002-03 to 111.4 in 2020-21. Sepsis-coded hospitalisations occurred more commonly in the elderly; those aged 65 years or above accounting for 20,573 (55.6%) sepsis-coded hospitalisations in 2002-03 and 86,135 (65.3%) in 2020-21. The cost of sepsis-coded hospitalisations increased at an annual rate of 20.6%, from AUD199M (€127 M) in financial year 2012 to AUD711M (€455 M) in 2019. CONCLUSION: Hospitalisations coded for sepsis and associated costs increased significantly from 2002 to 2021 and from 2012 to 2019, respectively.

Acute assessment of spinal cord injury in New South Wales: A retrospective study of current practice in two spinal cord injury referral centers.

INTRODUCTION: Interventions provided in the early phases after spinal cord injury (SCI) may improve neurological recovery and provide for best possible functional outcomes. Knowing this relies on early and clear documentation of the level and grade of the spinal cord injury. Guidelines advocate for early documentation of neurological status within 72 h of injury to allow early prognostication and to help guide initial management. It is unclear whether this is current practice in New South Wales (NSW). METHODS: Patients with acute SCI who were admitted to two SCI referral centers during 2018-2019 in NSW were included. Data relating to documentation of neurological status, timing of imaging, surgery and transfer to spinal cord injury center were collected and summarized using descriptive statistics. RESULTS: Only 18 percent of patients had an acceptable neurological examination according to the International Standards for Classification of Spinal Cord Injury (ISNCSCI) within 72 h of injury (either not done, or unable to determine the neurological level of injury). At the first neurological examination, the neurological level of injury and grade was unable to be determined in 26.8% of patients and 29.9% of patients respectively. At discharge from acute care and transfer to rehabilitation, the neurological level was undetermined in 28.9% of patients and grade undetermined in 26.8%. ISNCSCI examination was most commonly performed by spinal rehabilitation doctors after patients were discharged from the intensive care unit (ICU). CONCLUSIONS: Documentation of neurological level and grade of SCI within 72 h of injury is not being performed in the large majority of this cohort, which may impede evaluation of neurological improvement in response to acute treatment, and hinder prognostication.

Early sepsis in Australia and New Zealand: A point-prevalence study of haemodynamic resuscitation practices.

OBJECTIVE: Optimal resuscitation of sepsis-induced hypotension is uncertain, particularly the role of restrictive fluid strategies, leading to variability in usual practice. The objective of this study is to understand resuscitation practices in patients presenting to ED with early sepsis. METHODS: Design, participants and setting: Prospective, observational, multicentre, single-day, point-prevalence study enrolling adult patients present in 51 Australian and New Zealand ICUs at 10.00 hours, 8 June 2021. MAIN OUTCOME MEASURES: Site-level data on sepsis policies and patient-level demographic data, presence of sepsis and fluid and vasopressor administration in the first 24 h post-ED presentation. RESULTS: A total of 722 patients were enrolled. ED was the ICU admission source for 222 of 722 patients (31.2%) and 78 of 222 patients (35%) met the criteria for sepsis within 24 h of ED presentation. Median age of the sepsis cohort was 61 (48-72) years, 58% were male and respiratory infection was the commonest cause (53.8%). The sepsis cohort had a higher severity of illness than the non-sepsis cohort (144/222 patients) and chronic immunocompromise was more common. Of 78 sepsis patients, 55 (71%) received ≥1 fluid boluses with 500 and 1000 mL boluses equally common (both 49%). In the first 24 h, 2335 (1409-3125) mL (25.3 [13.2-42.9] mL/kg) was administered. Vasopressors were administered in 53 of 78 patients (68%) and for 25 patients (47%) administration was peripheral. CONCLUSIONS: ICU patients presenting to the ED with sepsis receive less fluids than current international recommendations and peripheral vasopressor administration is common. This finding supports the conduct of clinical trials evaluating optimal fluid dose and vasopressor timing for early sepsis-induced hypotension.

Blood Pressure Management Goals in Critically Ill Aneurysmal Subarachnoid Hemorrhage Patients in Australia and New Zealand.

INTRODUCTION: Blood pressure (BP) management is common in patients with aneurysmal subarachnoid hemorrhage (SAH) admitted to an intensive care unit. However, the practice patterns of BP management (timing, dose, and duration) have not been studied locally. METHODS: This post hoc analysis explored BP management goals (defined as the setting of a minimum systolic BP target or application of induced hypertension) in patients enrolled into the PROMOTE-SAH study in eleven neurosurgical centers in Australia and New Zealand. The primary outcome was 'dead or disabled' (modified Rankin Score ≥4) at 6 months, with the hypothesis being that setting BP management goals would be associated with improved outcomes. RESULTS: BP management goals were recorded in 266 of 357 (75%) patients, of which 149 were recorded as receiving induced hypertension for delayed cerebral ischemia (DCI) or vasospasm on 738 (19%) study days. In patients with a minimum systolic BP goal recorded (on 2067 d), the indication for the BP management goal was vasospasm or DCI on 651 (32%) days; no indication for BP management goals was documented on 1416 (69%) days. Crude analysis demonstrated an association between setting BP management goals and reduced death or disability (P=0.03), but this association was not significant after adjustment for the presence of DCI or vasospasm and clustered by the site. CONCLUSIONS: BP management goals are commonly 'prescribed' to aSAH patients admitted to an intensive care unit in Australia and New Zealand, but BP management goal setting was not associated with improved outcomes in the adjusted analysis.

Acetazolamide for metabolic alkalosis complicating respiratory failure with chronic obstructive pulmonary disease or obesity hypoventilation syndrome: a systematic review.

BACKGROUND: Metabolic alkalosis may lead to respiratory inhibition and increased need for ventilatory support or prolongation of weaning from ventilation for patients with chronic respiratory disease. Acetazolamide can reduce alkalaemia and may reduce respiratory depression. METHODS: We searched Medline, EMBASE and CENTRAL from inception to March 2022 for randomised controlled trials comparing acetazolamide to placebo in patients with chronic obstructive pulmonary disease, obesity hypoventilation syndrome or obstructive sleep apnoea, hospitalised with acute respiratory deterioration complicated by metabolic alkalosis. The primary outcome was mortality and we pooled data using random-effects meta-analysis. Risk of bias was assessed using the Cochrane RoB 2 (Risk of Bias 2) tool, heterogeneity was assessed using the I2 value and χ2 test for heterogeneity. Certainty of evidence was assessed using GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) methodology. RESULTS: Four studies with 504 patients were included. 99% of included patients had chronic obstructive pulmonary disease. No trials recruited patients with obstructive sleep apnoea. 50% of trials recruited patients requiring mechanical ventilation. Risk of bias was overall low to some risk. There was no statistically significant difference with acetazolamide in mortality (relative risk 0.98 (95% CI 0.28 to 3.46); p=0.95; 490 participants; three studies; GRADE low certainty) or duration of ventilatory support (mean difference -0.8 days (95% CI -7.2 to 5.6); p=0.36; 427 participants; two studies; GRADE: low certainty). CONCLUSION: Acetazolamide may have little impact on respiratory failure with metabolic alkalosis in patients with chronic respiratory diseases. However, clinically significant benefits or harms are unable to be excluded, and larger trials are required. PROSPERO REGISTRATION NUMBER: CRD42021278757.

Mortality and costs related to severe acute pancreatitis in the intensive care units of Australia and New Zealand (ANZ), 2003-2020.

BACKGROUND AND OBJECTIVE: Comprehensive data on the burden of severe acute pancreatitis (SAP) in global intensive care units (ICUs) and trends over time are lacking. Our objective was to compare trends in hospital and ICU mortality, in-hospital and ICU length of stay, and costs related to ICU admission in Australia and New Zealand (ANZ) for SAP. METHODS: We performed a retrospective, observational, cohort study of ICU admissions reported to the ANZ Intensive Care Society Adult Patient Database over three consecutive six-year time periods from 2003 to 2020. RESULTS: 12,635 patients with SAP from 189 ICUs in ANZ were analysed. No difference in adjusted hospital mortality (11.4% vs 11.5% vs 11.0%, p = 0.85) and ICU mortality rates (7.5% vs 8.0% vs 8.1%, p = 0.73) were noted over the study period. Median length of hospital admission reduced over time (13.9 days in 2003-08, 13.1 days in 2009-14 and 12.5 days in 2015-20; p < 0.01). No difference in length of ICU stay was noted over the study period (p = 0.13). The cost of managing SAP in ANZ ICUs remained constant over the three time periods. CONCLUSIONS: In critically-ill SAP patients in ANZ, no change in mortality has been noted over nearly two decades. There was a slight reduction in hospital stay (1 day), while the length of ICU stay remained unchanged. Given the significant costs related to care of patients with SAP in ICU, these findings highlight the need to prioritise resource allocation for healthcare delivery and targeted clinical research to identify treatments aimed at reducing mortality.

The association between ventriculostomy - Related infection and clinical outcomes: A systematic review and meta-analysis.

BACKGROUND: Ventriculostomy - related infection (VRI) is a common complication of patients who require placement of an external ventricular drain (EVD). The clinical outcomes of people who are diagnosed with VRI is poorly characterised. We performed a systematic review and meta-analysis to assess the association between VRI, and clinical outcomes and resource use, in patients treated with an EVD. METHODS: We searched MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of clinical trials to identify clinical trial and cohort studies that reported outcomes including mortality, functional outcome, duration of EVD insertion, and intensive care and hospital length of stay. Inclusion criteria and data extraction were conducted in duplicate. Where sufficient data were available, data synthesis was conducted using a random effects model to provide a pooled estimate of the association between VRI and clinical outcomes and resource use. We also pooled data to provide an estimate of the incidence of VRI in this population. RESULTS: Nineteen studies including 38,247 patients were included in the meta-analysis. There were twelve different definitions of VRI in the included studies. The pooled estimate of the incidence of VRI was 11 % (95 % confidence interval (CI), 9 % to 14 %). A diagnosis of VRI was not associated with an increase in the estimated odds ratio (OR) for mortality (OR 1.07, 95 % CI 0.59 to 1.92, p = 0.83 I2 = 83.5 %), nor was a diagnosis of VRI associated with changes in neurological outcome (OR 1.42, 95 % CI 0.36 to 5.56, p = 0.89, I2 = 0.3 %). Those diagnosed with VRI had longer intensive care unit length of stay (estimated pooled mean difference 8.4 days 95 % CI 3.4 to 13.4 days, p = 0.0009, I2 = 78.7 %) an increase in hospital length of stay (estimated mean difference 16.4 days. 95 % CI 11.6 to 21.2 days, p < 0.0005, I2 = 76.6 %), a prolonged duration of EVD placement (mean difference 5.24 days, 95 % CI 3.05 to 7.43, I2 = 78.2 %, p < 0.01), and an increased requirement for an internal ventricular shunt (OR 1.80, 95 % CI 1.32 to 2.46, I2 = 8.92 %, p < 0.01). CONCLUSIONS: Ventriculostomy related infection is not associated with increased mortality or an increased risk of poor neurological outcome, but is associated with prolonged duration of EVD placement, prolonged duration of ICU and hospital admission, and an increased rate of internal ventricular shunt placement.

Sepsis triggers and tools to support early identification in healthcare settings: An integrative review.

BACKGROUND: There is no universal trigger or tool to aid sepsis diagnosis. OBJECTIVES: The objective of this study was to identify triggers and tools to assist the early detection of sepsis that can be readily implemented across various health care settings. METHODS: A systematic integrative review was conducted using MEDLINE, CINAHL, EMBASE, Scopus, and the Cochrane Database of Systematic Reviews. Relevant grey literature and subject-matter expert consultation also informed the review. Study types included systematic reviews, randomised controlled trials, and cohort studies. All patient populations across prehospital, emergency department, and acute hospital inpatient settings, excluding the intensive care unit, were included. Sepsis triggers and tools were evaluated for efficacy in detecting sepsis and association with process measures and patient outcomes. Methodological quality was appraised using Joanna Briggs Institute tools. RESULTS: Of the 124 included studies, most were retrospective cohort (49.2%) in adults (83.9%) within the emergency department (44.4%). The most commonly evaluated sepsis tools were qSOFA (12 studies) and SIRS (11 studies) with a median sensitivity of 28.0% versus 51.0% and a specificity of 98.0% versus 82.0%, respectively, for sepsis diagnosis. Lactate plus qSOFA (two studies) had a sensitivity between 57.0 and 65.5%, whereas the National Early Warning Score (four studies) demonstrated median sensitivity and specificity >80%, but the latter was considered difficult to implement. Amongst triggers, lactate (18 studies) at the threshold of ≥2.0 mmol/L showed higher sensitivity for predicting sepsis-related clinical deterioration than <2.0 mmol/L. Automated sepsis alerts and algorithms (35 studies) showed median sensitivity between 58.0 and 80.0% and specificity between 60.0 and 93.1%. There were limited data for other sepsis tools and maternal, paediatric, and neonatal populations. Overall methodological quality was high. CONCLUSION: No single sepsis tool or trigger is applicable across various settings and populations, but considering efficacy and ease of implementation, there is evidence to use lactate plus qSOFA for adult patients. More research is needed in maternal, paediatric, and neonatal populations.

Quantification of changes in lung aeration associated with physiotherapy using lung ultrasound in mechanically ventilated patients: a prospective cohort study.

BACKGROUND: Lung ultrasound (LUS) is a novel and emerging tool for physiotherapists in ICU and may provide a way of monitoring lung aeration change in response to respiratory physiotherapy treatment during a patient's ICU stay. OBJECTIVE: To measure change in the LUS score associated with a respiratory physiotherapy treatment; to determine whether change in LUS score correlates with other physiological measures. DESIGN AND SETTING: A single-centre prospective cohort study was undertaken in a tertiary teaching hospital in Sydney, Australia. PATIENTS: Adult mechanically ventilated patients in ICU with suspicion of atelectasis. MEASUREMENTS: Primary outcome: pre-post difference in LUS score. SECONDARY OUTCOMES: PaO2/FiO2 (PF) ratio, tidal volume (VT), lung auscultation score, driving pressure (DP) and the modified radiological atelectasis score (mRAS) on CXR. RESULTS: 43 patients were included. There was a mean improvement in total LUS score after physiotherapy treatment of - 2.9 (95%CI -4.4, -1.4), and a mean improvement in LUS of the right and left lungs of - 1.6 (-2.5, -0.7) and - 1.3 (-2.5, -0.1) respectively. There was a mean improvement in PF ratio, VT and auscultation score of 10.4 (-11.89, 32.7), 19 (-7.4, 44.5) and - 1.8 (-2.6, -1.0) respectively. There was no improvement in mRAS or DP. There was a weak correlation between change in LUS score compared with change in mRAS score. LIMITATIONS: Limitations included the prospective cohort single site design and the small sample size. CONCLUSIONS: The LUS score can be used to detect changes in lung aeration associated with respiratory physiotherapy treatment for acute lobar atelectasis in mechanically ventilated patients. Australian and New Zealand Clinical Trials Registry Number: ACTRN12619000783123. CONTRIBUTION OF THE PAPER.

Impact of time of intensive care unit transfer and outcomes in patients with septic shock: An observational study.

OBJECTIVE: To evaluate the association between time from ED presentation to intensive care unit (ICU) transfer on mortality in patients presenting with septic shock. METHODS: Adult patients with suspected septic shock enrolled in the Australasian Resuscitation in Sepsis Evaluation trial were included. The primary outcome of this post-hoc analysis was 90-day mortality. ED-to-ICU time was analysed as both a continuous variable and a binary variable (≤ vs >4 h). Analysis incorporated mixed effects regression, with ICU site as a random effect, time-to-event analysis and competing risks regression; all with and without inverse probability of treatment weighting to account for confounding baseline covariates. RESULTS: Data from 1301 patients were included. Median (interquartile range [IQR]) ED-to-ICU time was 4.3 (3.1, 6.3) hours, with 588 patients (45%) transferred within 4 h. The ≤4-h group were younger, 64 (51, 74) versus 67 (52, 76) years (P = 0.04), with higher APACHE III scores, 50 (37, 65) versus 47 (35, 62) (P = 0.002), and higher unadjusted 90-day mortality, odds ratio (OR) 1.53 (95% confidence interval 1.15, 2.03), P = 0.01. After adjustment for pre-specified confounders, the 90-day mortality OR was 1.09 (0.83, 1.44), P = 0.52. Adjusted for death as a competing event and illness severity, hospital length of stay was similar between groups, whereas ICU duration remained longer for the ≤4-h group. CONCLUSION: In patients presenting to the ED with septic shock, ED-to-ICU time less than 4 h was not associated with altered 90-day mortality, although this should be interpreted with caution due to study limitations.

Barriers and facilitators to achieving competence in lung ultrasound: A survey of physiotherapists following a lung ultrasound training course.

BACKGROUND AND PURPOSE: Lung ultrasound (LUS) is an emerging tool for acute respiratory physiotherapists. In Australia, there are a select few LUS training courses run for physiotherapists. Research to date has evaluated LUS training courses for physiotherapists in terms of knowledge and skill acquisition. The impact of LUS training on user competence and confidence and whether LUS is used in clinical practice has yet to be evaluated. This study therefore explored the impact of attending a physiotherapy LUS training course on acquisition of competence and confidence and the barriers and facilitators for physiotherapists in achieving competence in LUS. METHODS: A quantitative survey containing 21 questions was distributed to 77 Australian physiotherapists. RESULTS: Of the invited physiotherapists, 39 (50%) completed the survey. Most participants were working in intensive care, in the public hospital setting. Binary logistic regression was performed and demonstrated no significant difference in the relationship between years of clinical experience and having confidence in performing or interpreting LUS images. There was also no statistical significance in the relationship between years of clinical experience and gaining competence and accreditation in LUS. Of the 39 responders, 20 physiotherapists had performed at least one LUS scan since completing training; however, most identified they never use LUS to inform clinical decision-making. Only one physiotherapist had gained accreditation through an ultrasound-governing body. The most frequently reported barriers to achieving competence were lack of clinical time to devote to training and lack of an LUS supervisor. CONCLUSION: A majority of physiotherapists who participated in an LUS training course did not attain competence or accreditation, nor were they confident in performing LUS and interpreting images. Barriers exist that prevent intensive care physiotherapists from being able to use LUS in clinical practice. LUS is also not frequently used by acute respiratory physiotherapists to make clinical decisions.