Publications by authors named "Rinaldo Bellomo"

1,228 Publications

  • Page 1 of 1

Urinary biomarkers to predict severe fluid overload after cardiac surgery: a pilot study.

Biomark Med 2021 Oct 21. Epub 2021 Oct 21.

Department of Cardiology, Brandenburg Heart Center, Immanuel Hospital, Ladeburger Str. 17, Bernau, 16321, Germany.

To assess the predictive ability of urinary and plasma biomarkers and clinical routine parameters for subsequent severe fluid overload. In a pilot study, we studied 100 adult patients after cardiac surgery. On intensive care unit admission, we measured biomarkers in urine (midkine, IL-6, neutrophil gelatinase-associated lipocalin [NGAL], hepcidin-25) and plasma (creatinine, urea, B-type natriuretic peptide, lactate, C-reactive protein, leukocytes, IL-6, NGAL, hepcidin-25) to predict postoperative severe fluid overload. Urinary midkine, IL-6, NGAL and hepcidin-25 (all AUCs ≥0.79) predicted postoperative severe fluid overload (N = 5 patients). Urinary NGAL/hepcidin-25 ratio (AUC 0.867) predicted postoperative severe fluid overload after adjustment to EuroScore and need for norepinephrine on surgery day (odds ratio: 2.4). Urinary biomarkers on intensive care unit admission might be helpful to predict subsequent severe fluid overload after cardiac surgery.
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http://dx.doi.org/10.2217/bmm-2021-0283DOI Listing
October 2021

The Impact of Normal Saline or Balanced Crystalloid on Plasma Chloride Concentration and Acute Kidney Injury in Patients With Predicted Severe Acute Pancreatitis: Protocol of a Phase II, Multicenter, Stepped-Wedge, Cluster-Randomized, Controlled Trial.

Front Med (Lausanne) 2021 4;8:731955. Epub 2021 Oct 4.

Department of Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.

The supraphysiologic chloride concentration of normal saline may contribute to acute kidney injury (AKI). Balanced crystalloids can decrease chloride concentration and AKI in critically ill patients. We aim to test the hypothesis that, in patients with predicted severe acute pancreatitis (pSAP), compared with saline, fluid therapy with balanced crystalloids will decrease plasma chloride concentration. This is a multicenter, stepped-wedge, cluster-randomized, controlled trial. All eligible patients presenting to the 11 participating sites across China during the study period will be recruited. All sites will use saline for the first month and sequentially change to balanced crystalloids at the pre-determined and randomly allocated time point. The primary endpoint is the plasma chloride concentration on day 3 of enrollment. Secondary endpoints will include major adverse kidney events on hospital discharge or day 30 (MAKE 30) and free and alive days to day 30 for intensive care admission, invasive ventilation, vasopressors, and renal replacement therapy. Additional endpoints include daily serum chloride and sequential organ failure assessment (SOFA) score over the first seven days of enrollment. This study will provide data to define the impact of normal saline vs. balanced crystalloids on plasma chloride concentration and clinical outcomes in pSAP patients. It will also provide the necessary data to power future large-scale randomized trials relating to fluid therapy. This study was approved by the ethics committee of Jinling Hospital, Nanjing University (2020NZKY-015-01) and all the participating sites. The results of this trial will be disseminated in peer-reviewed journals and at scientific conferences. The trial has been registered at the Chinese Clinical Trials Registry (ChiCTR2100044432).
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http://dx.doi.org/10.3389/fmed.2021.731955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521113PMC
October 2021

Opioid Prescription After Cardiac Surgery.

Heart Lung Circ 2021 Oct 14. Epub 2021 Oct 14.

Data Analytics Research and Evaluation (DARE) Centre, Austin Hospital and University of Melbourne, Melbourne, Vic, Australia; Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Vic, Australia; Department of Intensive Care, Austin Hospital, Melbourne, Vic, Australia; Department of Critical Care, The University of Melbourne, Melbourne, Vic, Australia.

Objectives: To characterise short-term and long-term opioid prescription patterns after cardiac surgery.

Design, Setting And Participants: We obtained data from a single Australian tertiary hospital from November 2012 to July 2019 and included 2,205 patients who underwent a primary cardiac surgical procedure.

Main Outcome And Measures: The primary outcome was the dose of opioids at hospital discharge. Secondary outcomes included factors associated with high dose opioid prescriptions and persistent opioids use after cardiac surgery.

Results: Overall, 76.4% of study patients were prescribed opioids at hospital discharge, with a median discharge prescription of 150 mg oral morphine equivalents. Moreover, 52.8% of discharge opioid prescriptions were as slow-release formulations and 60.0% of all discharge prescriptions were for patients who had received no opioids the day before discharge. In the subset of our patients with long-term data, 14.0% were still receiving opioids at 3-12 months after cardiac surgery.

Conclusions: In cardiac surgical patients, opioid prescriptions at discharge were common, most were at higher than recommended doses and more than half were slow-release formulations. Such prescription was associated with one in seven patients continuing to receive opioids 3-12 months after surgery.
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http://dx.doi.org/10.1016/j.hlc.2021.08.022DOI Listing
October 2021

Rapid Evaluation of Coronavirus Illness Severity (RECOILS) in intensive care: Development and validation of a prognostic tool for in-hospital mortality.

Acta Anaesthesiol Scand 2021 Oct 8. Epub 2021 Oct 8.

Intensive Care, Reinier de Graaf Gasthuis, Delft, The Netherlands.

Background: The prediction of in-hospital mortality for ICU patients with COVID-19 is fundamental to treatment and resource allocation. The main purpose was to develop an easily implemented score for such prediction.

Methods: This was an observational, multicenter, development, and validation study on a national critical care dataset of COVID-19 patients. A systematic literature review was performed to determine variables possibly important for COVID-19 mortality prediction. Using a logistic multivariable model with a LASSO penalty, we developed the Rapid Evaluation of Coronavirus Illness Severity (RECOILS) score and compared its performance against published scores.

Results: Our development (validation) cohort consisted of 1480 (937) adult patients from 14 (11) Dutch ICUs admitted between March 2020 and April 2021. Median age was 65 (65) years, 31% (26%) died in hospital, 74% (72%) were males, average length of ICU stay was 7.83 (10.25) days and average length of hospital stay was 15.90 (19.92) days. Age, platelets, PaO2/FiO2 ratio, pH, blood urea nitrogen, temperature, PaCO2, Glasgow Coma Scale (GCS) score measured within +/-24 h of ICU admission were used to develop the score. The AUROC of RECOILS score was 0.75 (CI 0.71-0.78) which was higher than that of any previously reported predictive scores (0.68 [CI 0.64-0.71], 0.61 [CI 0.58-0.66], 0.67 [CI 0.63-0.70], 0.70 [CI 0.67-0.74] for ISARIC 4C Mortality Score, SOFA, SAPS-III, and age, respectively).

Conclusions: Using a large dataset from multiple Dutch ICUs, we developed a predictive score for mortality of COVID-19 patients admitted to ICU, which outperformed other predictive scores reported so far.
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http://dx.doi.org/10.1111/aas.13991DOI Listing
October 2021

The comparative epidemiology and outcomes of hospitalized patients treated with SGLT2 or DPP4 inhibitors.

J Diabetes Complications 2021 Sep 27:108052. Epub 2021 Sep 27.

Department of Medicine, The University of Melbourne, Melbourne, Australia; Department of Endocrinology, Austin Health, Melbourne, Australia.. Electronic address:

Objective: To compare the outcomes of sodium glucose linked cotransporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase 4 inhibitors (DPP4i) in hospitalized patients.

Research Design And Methods: Electronic medical records-based cohort study. Identification of patients with type 2 diabetes and treatment with SGLT2i (n = 466) or DPP4i (n = 1541). Outcomes compared between those who received SGLT2i and those who received DPP4i. The primary outcome: adjusted percentage of blood glycemia within 4-10 mmol/L.

Results: After adjustment, SGLT2i use had a statistically equivalent percentage of glycemia within range (coefficient: 4.55, 95% CI -3.23 to 12.32, p = 0.25) or <4 mmol/L (coefficient -0.17, 95% CI -0.71 to 3.72, p = 0.54). There were no significant differences in hospital length of stay (p = 0.22), complications, (p = 0.11) or mortality (p = 0.57). When measured, ketone levels were higher in the SGLT2i group on admission, but lower on days 3, 4 and 5 (p < 0.001 for interaction). Bicarbonate levels were not statistically different between groups. Finally, 54% of patients whose SGLT2i was ceased during admission, were discharged home without it.

Conclusion: Among inpatients with type 2 diabetes, SGLT2i use was associated with equivalent within-target glycaemia and no significant increase in hypoglycemia, ketonemia, or lower bicarbonate levels. These hypothesis-generating findings support further investigation of SGLT2i therapy in inpatients.
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http://dx.doi.org/10.1016/j.jdiacomp.2021.108052DOI Listing
September 2021

Machine Learning in Risk Prediction for Cardiac Surgery - An Emerging Trend?

Heart Lung Circ 2021 Sep 28. Epub 2021 Sep 28.

Intensive Care Research, University of Melbourne, Melbourne, Monash University, Melbourne, Vic, Australia.

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http://dx.doi.org/10.1016/j.hlc.2021.09.007DOI Listing
September 2021

Intra-operative ventilator mechanical power as a predictor of postoperative pulmonary complications in surgical patients: A secondary analysis of a randomised clinical trial.

Eur J Anaesthesiol 2021 Sep 22. Epub 2021 Sep 22.

From the Department of Anaesthesia (DK, LW, PP, LE, RH, BP, COT, DS, MOD, PH, CO, JG), Department of Intensive Care, Austin Hospital (DK, ASN, AW, GE, RB, DAJ), Department of Critical Care (DK, ASN, PP, LE, RH, BP, COT, DS, RB), Department of Surgery, University of Melbourne (LW, LE, RH, BP, COT), Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University (ASN, RB, DAJ), Data Analytics Research and Evaluation (DARE) Centre, University of Melbourne, Melbourne, Victoria, Australia (ASN, RB) and Department of Critical Care Medicine, Hospital Israelita Albert Einstein, São Paulo, Brazil (ASN).

Background: Studies in critically ill patients suggest a relationship between mechanical power (an index of the energy delivered by the ventilator, which includes driving pressure, respiratory rate, tidal volume and inspiratory pressure) and complications.

Objective: We aimed to assess the association between intra-operative mechanical power and postoperative pulmonary complications (PPCs).

Design: Post hoc analysis of a large randomised clinical trial.

Setting: University-affiliated academic tertiary hospital in Melbourne, Australia, from February 2015 to February 2019.

Patients: Adult patients undergoing major noncardiothoracic, nonintracranial surgery.

Intervention: Dynamic mechanical power was calculated using the power equation adjusted by the respiratory system compliance (CRS). Multivariable models were used to assess the independent association between mechanical power and outcomes.

Main Outcome Measures: The primary outcome was the incidence of PPCs within the first seven postoperative days. The secondary outcome was the incidence of acute respiratory failure.

Results: We studied 1156 patients (median age [IQR]: 64 [55 to 72] years, 59.5% men). Median mechanical power adjusted by CRS was 0.32 [0.22 to 0.51] (J min-1)/(ml cmH2O-1). A higher mechanical power was also independently associated with increased risk of PPCs [odds ratio (OR 1.34, 95% CI, 1.17 to 1.52); P < 0.001) and acute respiratory failure (OR 1.40, 95% CI, 1.21 to 1.61; P < 0.001).

Conclusion: In patients receiving ventilation during major noncardiothoracic, nonintracranial surgery, exposure to a higher mechanical power was independently associated with an increased risk of PPCs and acute respiratory failure.

Trial Registration: Australia and New Zealand Clinical Trials Registry no: 12614000790640.
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http://dx.doi.org/10.1097/EJA.0000000000001601DOI Listing
September 2021

A Phase II Cluster-Crossover Randomized Trial of Fentanyl vs. Morphine for Analgosedation in Mechanically Ventilated Patients.

Am J Respir Crit Care Med 2021 Sep 20. Epub 2021 Sep 20.

Austin Health, 3805, Intensive Care, Heidelberg, Victoria, Australia.

Rationale: The continuous infusion of fentanyl or morphine is often prescribed to assist with analgesia and sedation (analgosedation) during mechanical ventilation.

Objectives: To compare the effect of fentanyl vs. morphine on patient-centered outcomes in ventilated patients.

Methods: We conducted a cluster-randomized, cluster-crossover trial between July 2019 and August 2020 in two adult Intensive Care Units. We compared two continuous infusion regimens (fentanyl vs. morphine). One Intensive Care Unit was randomized to the fentanyl-morphine sequence and the other to the morphine-fentanyl sequence. The primary outcome was the number of ventilator free days at day 28. Secondary outcomes included, among others, duration of mechanical ventilation in survivors and Intensive Care Unit free days at day 28.

Measurements And Main Results: Via cluster allocation, we randomized 737 patients. Of these, 56 were excluded due to the opt-out consent process, leaving 681 (344 to fentanyl and 337 to morphine) for primary analysis (median [IQR] age, 59 [44-69] years). Median ventilator free days at day 28 were 26.1 (20.7-27.3) in the fentanyl vs 25.3 (19.1-27.2) in the morphine group (median difference, 0.79 [95% CI, 0.31 to 1.28], p=0.001). Intensive Care Unit-free days were greater (P<0.001) and Intensive Care Unit length of stay in survivors shorter (P<0.001) in the fentanyl group. All other secondary outcomes were not statistically different by treatment group.

Conclusions: Among adult patients requiring mechanical ventilation, compared with morphine, fentanyl infusion significantly increased the median number of ventilator free days at day 28. The choice of opioid infusion agent may affect clinical outcomes and requires further investigation. Clinical trial registration available at https://www.anzctr.org.au/, ID: ACTRN12619000939190.
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http://dx.doi.org/10.1164/rccm.202106-1515OCDOI Listing
September 2021

Urinary Neutrophil Gelatinase-Associated Lipocalin/Hepcidin-25 Ratio for Early Identification of Patients at Risk for Renal Replacement Therapy After Cardiac Surgery: A Substudy of the BICARBONATE Trial.

Anesth Analg 2021 Sep 20. Epub 2021 Sep 20.

Department of Anesthesiology and Intensive Care, Helios Klinikum Leisnig, Leisnig, Germany.

Background: Acute kidney injury requiring renal replacement therapy (AKI-RRT) is strongly associated with mortality after cardiac surgery; however, options for early identification of patients at high risk for AKI-RRT are extremely limited. Early after cardiac surgery, the predictive ability for AKI-RRT even of one of the most extensively evaluated novel urinary biomarkers, neutrophil gelatinase-associated lipocalin (NGAL), appears to be only moderate. We aimed to determine whether the NGAL/hepcidin-25 ratio (urinary concentrations of NGAL divided by that of hepcidin-25) early after surgery may compare favorably to NGAL for identification of high-risk patients after cardiac surgery.

Methods: This is a prospective substudy of the BICARBONATE trial, a multicenter parallel-randomized controlled trial comparing perioperative bicarbonate infusion for AKI prevention to usual patient care. At a tertiary referral center, 198 patients at increased kidney risk undergoing cardiac surgery with cardiopulmonary bypass were included into the present study. The primary outcome measure was defined as AKI-RRT. Secondary outcomes were in-hospital mortality and long-term mortality. We compared area under the curve of the receiver operating characteristic (AUC-ROC) of urinary NGAL with that of the urinary NGAL/hepcidin-25 ratio within 60 minutes after end of surgery. We compared adjusted AUC and performed cross-validated reclassification statistics of the (logarithmic) urinary NGAL/hepcidin-25 ratio adjusted to Cleveland risk score/EuroScore, cross-clamp time, age, volume of packed red blood cells, and (logarithmic) urinary NGAL concentration. The association of the NGAL/hepcidin-25 ratio with long-term patient survival was assessed using Cox proportional hazard regression analysis adjusting for EuroScore, aortic cross-clamp time, packed red blood cells and urinary NGAL.

Results: Patients with AKI-RRT (n = 13) had 13.7-times higher NGAL and 3.3-times lower hepcidin-25 concentrations resulting in 46.9-times higher NGAL/hepcidin-25 ratio early after surgery compared to patients without AKI-RRT. The NGAL/hepcidin-25 ratio had higher AUC-ROC compared with NGAL for risk of AKI-RRT and in-hospital mortality (unadjusted AUC-ROC difference 0.087, 95% confidence interval [CI], 0.036-0.138, P < .001; 0.082, 95% CI, 0.018-0.146, P = .012). For AKI-RRT, the NGAL/hepcidin-25 ratio increased adjusted category-free net reclassification improvement (cfNRI; 0.952, 95% CI, 0.437-1.468; P < .001) and integrated discrimination improvement (IDI; 0.040, 95% CI, 0.008-0.073; P = .016) but not AUC difference. For in-hospital mortality, the ratio improved AUC of the reference model (AUC difference 0.056, 95% CI, 0.003-0.108; P = .037) and cfNRI but not IDI. The urinary NGAL/hepcidin-25 ratio remained significantly associated with long-term mortality after adjusting for the model covariates.

Conclusions: The urinary NGAL/hepcidin-25 ratio appears to early identify high-risk patients and outperform NGAL after cardiac surgery. Confirmation of our findings in other cardiac surgery centers is now needed.
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http://dx.doi.org/10.1213/ANE.0000000000005741DOI Listing
September 2021

An Update on Temperature Management Following Cardiac Arrest in Australian and New Zealand ICUs.

Crit Care Med 2021 10;49(10):e1040-e1042

Intensive Care Research Programme, Medical Research Institute of New Zealand, Wellington, New Zealand.

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http://dx.doi.org/10.1097/CCM.0000000000005114DOI Listing
October 2021

Platelet Decreases following Continuous Renal Replacement Therapy Initiation as a Novel Risk Factor for Renal Nonrecovery.

Blood Purif 2021 Sep 14:1-8. Epub 2021 Sep 14.

The Renal and Metabolic Division, The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia.

Background: Continuous renal replacement therapy (CRRT) is a form of dialysis used in critically ill patients, and has recently been associated with renal nonrecovery. Decreases in platelets following CRRT initiation are common and are associated with mortality, but associations with renal recovery are unclear. Our objective was to determine if platelet nadir or the degree of platelet decrease following CRRT initiation was associated with renal nonrecovery.

Methods: This is a secondary analysis of the Randomized Evaluation of Normal versus Augmented Level (RENAL) trial. Primary predictors were platelet nadir discretized by median value and percent platelet decrease following CRRT initiation, with cut points evaluated by decile from 30 to 60%. The 2 primary outcomes were time to RRT-independence and RRT-free days. Secondary outcomes were 28-day mortality, 90-day mortality, intensive care unit (ICU)-free, and hospital-free days.

Results: Time to RRT independence censored for death was achieved less frequently in patients with low platelet nadir (hazard ratio [HR] 0.77, confidence interval [CI] 0.66-0.91) and in those with >50% platelet decrease (HR 0.84, CI 0.72-0.97). RRT-free days were lower in both low platelet nadir (odds ratio [OR] 0.94, CI 0.90-0.97) and >50% platelet decrease (OR 0.91, CI 0.88-0.95). These groups also had higher rates of 28- and 90-day mortality and fewer ICU-free and hospital-free days. Thrombocytopenia at CRRT initiation was also associated with renal nonrecovery, although the clinical effect was small.

Conclusions: Platelet nadir <100 × 103/µL and platelet decrease by >50% following CRRT initiation were both associated with lower rates of renal recovery. Further research is needed to evaluate mechanisms-linking platelet changes and renal nonrecovery in CRRT.
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http://dx.doi.org/10.1159/000517232DOI Listing
September 2021

Hyperoncotic Albumin Solution in Continuous Renal Replacement Therapy Patients.

Blood Purif 2021 Aug 12:1-10. Epub 2021 Aug 12.

Department of Intensive Care, Austin Hospital, Melbourne, Victoria, Australia.

Aim: The aim of this study was to investigate the association of hyperoncotic (20%) human albumin solution (HAS) with outcomes among critically ill patients receiving continuous renal replacement therapy (RRT).

Methods: Analysis of the Randomized Evaluation of Normal versus Augmented Level (RENAL) RRT trial data.

Results: Of 1,508 patients, 771 (51%) received albumin. Of these, 345 (45%) received 4% HAS only, 155 (20%) received 20% HAS only, and 271 (35%) received both. Patients who received combined 4% and 20% HAS were more severely ill, received more days of RENAL trial therapy and required mechanical ventilation for longer. Mean daily fluid balance was -288 mL (-904 to 261) with 20% HAS only versus 245 mL (-248 to 1,050) with 4% HAS only (p < 0.001). On Cox proportional hazards regression, 20% HAS exposure was not associated with greater 90-day mortality (odds ratio 1.12, 95% confidence interval [CI]: 0.77-1.62; p = 0.55) or longer recovery to RRT independence (sub-hazard ratio 1.04, 95% CI: 0.84-1.30; p = 0.70) compared to those who received 4% HAS only.

Conclusions: RENAL trial patients commonly received albumin in varying concentrations. The administration of 20% HAS was associated with a more negative fluid balance but was not independently associated with increased mortality or RRT dependence when compared to 4% HAS only.
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http://dx.doi.org/10.1159/000517957DOI Listing
August 2021

Calcium administration In patients undergoing CardiAc suRgery under cardiopulmonary bypasS (ICARUS trial): Rationale and design of a randomized controlled trial.

Contemp Clin Trials Commun 2021 Sep 18;23:100835. Epub 2021 Aug 18.

IRCCS San Raffaele Scientific Institute, Milan, Italy.

Introduction: Weaning from cardiopulmonary bypass (CPB) is a critical step of any cardiac surgical procedure and often requires pharmacologic intervention. Calcium ions are pivotal elements for the excitation-contraction coupling process of cardiac myocytes. Thus, calcium administration might be helpful during weaning from CPB.

Methods: We describe a multicenter, placebo-controlled, double blind randomized clinical trial to assess the effect of calcium chloride on the need for inotropic support among adult patients during weaning from CPB. The experimental group (409 patients) will receive 15 mg/kg of calcium chloride. The control group (409 patients) will receive an equivalent volume of 0.9% sodium chloride. Both drugs will be administered intravenously as a bolus at the beginning of weaning from CPB.

Results: The primary outcome will be the need for inotropic support between termination of CPB and completion of surgery. Secondary outcomes will be: duration of inotropic support, vasoactive-inotropic score 30 min after transfer to intensive care unit and on postoperative day 1, plasma alpha-amylase on postoperative day 1, plasma Ca concentration immediately before and 10-15 min after calcium chloride administration, non-fatal myocardial infarction, blood loss on postoperative day 1, need for transfusion of red blood cells, signs of myocardial ischemia on electrocardiogram after arrival to intensive care unit, all-cause mortality at 30 days or during hospital stay if this is longer than 30 days.

Discussion: This trial is designed to assess whether intravenous calcium chloride administration could reduce the need for inotropic support after cardiopulmonary bypass weaning among adults undergoing cardiac surgery.
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http://dx.doi.org/10.1016/j.conctc.2021.100835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406154PMC
September 2021

Thromboelastography in elective total hip arthroplasty.

World J Orthop 2021 Aug 18;12(8):555-564. Epub 2021 Aug 18.

Department of Anesthesia, Austin Health, Heidelberg 3084, Victoria, Australia.

Background: Hypercoagulability plays an important role in predisposing patients to venous thromboembolism (VTE) after total hip arthroplasty (THA). We used thromboelastography (TEG) to examine the coagulation status of patients undergoing THA.

Aim: To examine coagulation as measured by TEG in patients undergoing THA who received standard VTE chemoprophylaxis with enoxaparin.

Methods: After ethical approval, we performed a retrospective analysis of data collected in patients undergoing primary elective THA. We analyzed TEG data on samples performed before skin incision, intraoperatively and for 5 d postoperatively. Conventional coagulation tests were performed preoperatively and on postoperative day 5.

Results: Twenty patients undergoing general anesthesia and 32 patients undergoing spinal anesthesia (SA) were included. TEG demonstrated a progressively hypercoagulable state postoperatively, characterized by elevated maximum amplitude. TEG also demonstrated transient intraoperative hypercoagulability in patients receiving SA. In contrast, conventional coagulation tests were normal in all patients, pre- and postoperatively, except for an increase in plasma fibrinogen day 5 postoperatively.

Conclusion: Despite VTE prophylaxis, patients following total hip replacement remain in a hypercoagulable state as measured by both TEG and conventional tests. This group may benefit from more optimal anticoagulation and/or additional perioperative hemostatic monitoring, TEG or otherwise.
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http://dx.doi.org/10.5312/wjo.v12.i8.555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384610PMC
August 2021

The hemodynamic effects of intravenous paracetamol (acetaminophen) in patients with chronic liver disease undergoing liver transplantation: a pilot study.

BMC Res Notes 2021 Aug 24;14(1):325. Epub 2021 Aug 24.

Department of Intensive Care, Austin Hospital, Heidelberg, VIC, Australia.

Objective: We performed a single-center double-blinded, randomized trial to investigate the hemodynamic effects of IV paracetamol in patients with chronic liver disease (CLD) undergoing liver transplantation surgery. Patients with CLD are particularly susceptible to hemodynamic derangements given their low systemic vascular resistance state. Accordingly, hypotension is common in this setting. The hemodynamic effects of IV paracetamol in patients undergoing elective liver transplantation are unknown, therefore we evaluated whether the intraoperative administration of IV paracetamol in patients with chronic liver disease undergoing liver transplantation results in adverse hemodynamic effects. The primary end point was a change in systolic blood pressure 30-min after the preoperative infusion.

Results: Twenty-four participants undergoing liver transplantation surgery were randomly assigned to receive a single bolus of IV paracetamol (1 g paracetamol + 3.91 g mannitol per 100 mL) (n = 12) or placebo (0.9% Saline 100 mL) (n = 12). All participants completed their study intervention, and there were no breaches or violations of the trial protocol. Baseline characteristics were similar in both groups. There were no significant differences regarding surgical duration, intraoperative use of fluids, and intraoperative noradrenaline use. After the administration of paracetamol there were no significant differences observed in blood pressure or other hemodynamic parameters when compared to placebo.
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http://dx.doi.org/10.1186/s13104-021-05749-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383248PMC
August 2021

Predicting atrial fibrillation after cardiac surgery: a scoping review of associated factors and systematic review of existing prediction models.

Perfusion 2021 Aug 18:2676591211037025. Epub 2021 Aug 18.

Department of Epidemiology and Preventative Medicine, Monash University, Melbourne, VIC, Australia.

Introduction: Postoperative atrial fibrillation (POAF) is common after cardiac surgery and associated with increased hospital length of stay, patient morbidity and mortality. We aimed to identify factors associated with POAF and evaluate the accuracy of available POAF prediction models.

Methods: We screened articles from Ovid MEDLINE and PubMed Central (PMC) and included studies that evaluated risk factors associated with POAF or studies that designed or validated POAF prediction models. We only included studies in cardiac surgical patients with sample size ⩾ 50 and a POAF outcome group ⩾20. We summarised factors that were associated with POAF and assessed prediction model performance by reviewing reported calibration and discriminative ability.

Results: We reviewed 232 studies. Of these, 142 fulfilled the inclusion criteria. Age was frequently found to be associated with POAF, while most other variables showed contradictory findings, or were assessed in few studies. Overall, 15 studies specifically developed and/or validated 12 prediction models. Of these, all showed poor discrimination or absent calibration in predicting POAF in externally validated cohorts.

Conclusions: Except for age, reporting of factors associated with POAF is inconsistent and often contradictory. Prediction models have low discrimination, missing calibration statistics, are at risk of bias and show limited clinical applicability. This suggests the need for studies that prospectively collect AF relevant data in large cohorts and then proceed to validate findings in external data sets.
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http://dx.doi.org/10.1177/02676591211037025DOI Listing
August 2021

A comparison of the hemodynamic effects of fluid bolus therapy with crystalloids vs. 4% albumin and vs. 20% albumin in patients after cardiac surgery.

Heart Lung 2021 Nov-Dec;50(6):870-876. Epub 2021 Aug 14.

Department of Intensive Care, Austin Hospital, Melbourne, VIC, Australia; Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), School of Public Health and Preventive Medicine, Monash University, Australia; Centre for Integrated Critical Care, School of Medicine, University of Melbourne, Parkville, Victoria, Australia. Electronic address:

Background: Crystalloids, 4% albumin and 20% albumin are used for fluid bolus therapy (FBT) in patients after cardiac surgery. However, their detailed early (30 min) hemodynamic effects remain unstudied.

Methods: In a comparative prospective observational trial of 120 ventilated, we studied post cardiac surgery patients who received crystalloid 500 ml FBT, 4% albumin 500 ml FBT or 20% albumin 100 ml FBT (40 per group). We recorded second-by-second hemodynamic parameters and 15-minutely cardiac index (CI) data before and for 30 min after FBT. We compared the crystalloid group (reference) vs. the 4% albumin group, and vs. the 20% albumin group.

Results: Immediately after FBT, the mean (standard deviation) CI increase was 0.4 (0.4) L/min/m with crystalloids, 0.4 (0.5) L/min/m with 4% albumin and 0.3 (0.4) L/min/m with 20% albumin, despite the much smaller FBT volume with 20% albumin. Mean arterial pressure (MAP) increase was 11 (10), 12 (9) and 9 (6) mm Hg, respectively. There was no group effect or interaction for changes in CI. However, there were time-group interactions for MAP changes such that crystalloid FBT had faster MAP reduction than 4% (p<0.001) or 20% albumin (p < 0.001). Moreover, patients treated with crystalloid FBT showed a faster decline in central venous pressure, perfusion pressure than the two groups. Finally, 20% albumin attenuated the fall in temperature induced by FBT.

Conclusion: In postoperative cardiac surgery patients, after a similar initial CI and MAP response, the MAP effect of crystalloid FBT dissipates faster than that of 4% or 20% albumin FBT. These findings can be used to inform clinical practice.
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http://dx.doi.org/10.1016/j.hrtlng.2021.07.014DOI Listing
August 2021

A multicenter randomized clinical trial of pharmacological vitamin B1 administration to critically ill patients who develop hypophosphatemia during enteral nutrition (The THIAMINE 4 HYPOPHOSPHATEMIA trial).

Clin Nutr 2021 08 24;40(8):5047-5052. Epub 2021 Jul 24.

The University of Melbourne, Department of Critical Care, Melbourne Medical School, Melbourne, Australia; Intensive Care Unit, Royal Melbourne Hospital, Melbourne, Australia.

Background: Hypophosphatemia may be a useful biomarker to identify thiamine deficiency in critically ill enterally-fed patients. The objective was to determine whether intravenous thiamine affects blood lactate, biochemical and clinical outcomes in this group.

Method: This randomized clinical trial was conducted across 5 Intensive Care Units. Ninety critically ill adult patients with a serum phosphate ≤0.65 mmol/L within 72 h of commencing enteral nutrition were randomized to intravenous thiamine (200 mg every 12 h for up to 14 doses) or usual care (control). The primary outcome was blood lactate over time and data are median [IQR] unless specified.

Results: Baseline variables were well balanced (thiamine: lactate 1.2 [1.0, 1.6] mmol/L, phosphate 0.56 [0.44, 0.64] mmol/L vs. control: lactate 1.0 [0.8, 1.3], phosphate 0.54 [0.44, 0.61]). Patients randomized to the intervention received a median of 11 [7.5, 13.5] doses for a total of 2200 [1500, 2700] mg of thiamine. Blood lactate over the entire 7 days of treatment was similar between groups (mean difference = -0.1 (95 % CI -0.2 to 0.1) mmol/L; P = 0.55). The percentage change from lactate pre-randomization to T = 24 h was not statistically different (thiamine: -32 (-39, -26) vs. control: -24 (-31, -16) percent, P = 0.09). Clinical outcomes were not statistically different (days of vasopressor administration: thiamine 2 [1, 4] vs. control 2 [0, 5.5] days; P = 0.37, and deaths 9 (21 %) vs. 5 (11 %); P = 0.25).

Conclusions: In critically ill enterally-fed patients who developed hypophosphatemia, intravenous thiamine did not cause measurable differences in blood lactate or clinical outcomes.

Trial Registration: Australian and New Zealand Clinical Trials Registry (ACTRN12619000121167).
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http://dx.doi.org/10.1016/j.clnu.2021.07.024DOI Listing
August 2021

An Exploratory Analysis of the Association between Hypercapnia and Hospital Mortality in Critically Ill Patients with Sepsis.

Ann Am Thorac Soc 2021 Aug 11. Epub 2021 Aug 11.

Austin Hospital, 96043, Heidelberg, Victoria, Australia.

Rationale: Hypercapnia may affect the outcome of sepsis. Very few clinical studies conducted in non-critically ill patients, have investigated the effects of hypercapnia and hypercapnic acidemia in the context of sepsis. The effect of hypercapnia in critically ill patients with sepsis remains inadequately studied.

Objective: To investigate the association of hypercapnia with hospital mortality in septic critically ill patients.

Methods: This is a retrospective study conducted in three tertiary public hospitals. Septic critically ill patients from three intensive care units between January 2011 and May 2019 were included. Five cohorts (exposure of at least 24, 48, 72, 120 and 168 hours) were created to account for immortal time bias and informative censoring. The association between hypercapnia exposure and hospital mortality was assessed with multivariable models. Subgroup analyses compared ventilated vs. non-ventilated and pulmonary vs. non-pulmonary sepsis patients.

Results: We analyzed 84,819 PaCO2 measurements in 3,153 patients (57.6% male; median age was 62.5 years). After adjustment for key confounders, both in mechanically ventilated and non-ventilated patients and in patients with pulmonary sepsis, there was no independent association of hypercapnia with hospital mortality. In contrast, in ventilated patients, the presence of prolonged exposure to both hypercapnia and acidemia was associated with increased mortality (highest Odds Ratio of 16.5 for at least 120 hours of potential exposure; P = 0.007).

Conclusion: After adjustment, isolated hypercapnia was not associated with increased mortality in septic patients. These hypothesis-generating observations suggest that as hypercapnia is not an independent risk factor for mortality, trials of permissive hypercapnia in sepsis may be safe.
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http://dx.doi.org/10.1513/AnnalsATS.202102-104OCDOI Listing
August 2021

Reversal of renal tissue hypoxia during experimental cardiopulmonary bypass in sheep by increased pump flow and arterial pressure.

Acta Physiol (Oxf) 2021 04 22;231(4):e13596. Epub 2020 Dec 22.

Pre-Clinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia.

Aim: Renal tissue hypoxia during cardiopulmonary bypass could contribute to the pathophysiology of acute kidney injury. We tested whether renal tissue hypoxia can be alleviated during cardiopulmonary bypass by the combined increase in target pump flow and mean arterial pressure.

Methods: Cardiopulmonary bypass was established in eight instrumented sheep under isoflurane anaesthesia, at a target continuous pump flow of 80 mL·kg min and mean arterial pressure of 65 mmHg. We then tested the effects of simultaneously increasing target pump flow to 104 mL·kg min and mean arterial pressure to 80 mmHg with metaraminol (total dose 0.25-3.75 mg). We also tested the effects of transitioning from continuous flow to partially pulsatile flow (pulse pressure ~15 mmHg).

Results: Compared with conscious sheep, at the lower target pump flow and mean arterial pressure, cardiopulmonary bypass was accompanied by reduced renal blood flow (6.8 ± 1.2 to 1.95 ± 0.76 mL·min kg) and renal oxygen delivery (0.91 ± 0.18 to 0.24 ± 0.11 mL·O min kg). There were profound reductions in cortical oxygen tension (PO) (33 ± 13 to 6 ± 6 mmHg) and medullary PO (31 ± 12 to 8 ± 8 mmHg). Increasing target pump flow and mean arterial pressure increased renal blood flow (to 2.6 ± 1.0 mL·min kg) and renal oxygen delivery (to 0.32 ± 0.13 mL·O minkg) and returned cortical PO to 58 ± 60 mmHg and medullary PO to 28 ± 16 mmHg; levels similar to those of conscious sheep. Partially pulsatile pump flow had no significant effects on renal perfusion or oxygenation.

Conclusions: Renal hypoxia during experimental CPB can be corrected by increasing target pump flow and mean arterial pressure within a clinically feasible range.
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http://dx.doi.org/10.1111/apha.13596DOI Listing
April 2021

The impact of distance on post-ICU disability.

Aust Crit Care 2021 Jul 25. Epub 2021 Jul 25.

Australian and New Zealand Intensive Care Research Centre, Melbourne, Australia; The Alfred Hospital, Melbourne, Australia; Monash Partners Academic Health Science Centre, Australia. Electronic address:

Background: Nonurban residential living is associated with adverse outcomes for a number of chronic health conditions. However, it is unclear what effect it has amongst survivors of critical illness.

Objectives: The purpose of this study is to determine whether patients living greater than 50 km from the treating intensive care unit (ICU) have disability outcomes at 6 months that differ from people living within 50 km.

Methods: This was a multicentre, prospective cohort study conducted in five metropolitan ICUs. Participants were adults admitted to the ICU, who received >24 h of mechanical ventilation and survived to hospital discharge. In a secondary analysis of these data, the cohort was dichotomised based on residential distance from the treating ICU: <50 km and ≥50 km. The primary outcome was patient-reported disability using the 12-item World Health Organization's Disability Assessment Schedule (WHODAS 2.0). This was recorded at 6 months after ICU admission by telephone interview. Secondary outcomes included health status as measured by EQ-5D-5L return to work and psychological function as measured by the Hospital Anxiety and Depression Scale (HADS). Multivariable logistic regression was used to assess the association between distance from the ICU and moderate to severe disability, adjusted for potential confounders. Variables included in the multivariable model were deemed to be clinically relevant and had baseline imbalance between groups (p < 0.10). These included marital status and hours of mechanical ventilation. Sensitivity analysis was also conducted using distance in kilometres as a continuous variable.

Results: A total of 262 patients were enrolled, and 169 (65%) lived within 50 km of the treating ICU and 93 (35%) lived ≥50 km from the treating ICU (interquartile range [IQR] 10-664 km). There was no difference in patient-reported disability at 6 months between patients living <50 km and those living ≥50 km (WHODAS total disability % [IQR] 10.4 [2.08-25] v 14.6 [2.08-20.8], P = 0.74). There was also no difference between groups for the six major life domains of the WHODAS. There was no difference in rates of anxiety or depression as measured by HADS score (HADS anxiety median [IQR] 4 [1-7] v 3 [1-7], P = 0.60) (HADS depression median [IQR] 3 [1-6] v 3 [1-6], P = 0.62); health status as measured by EQ-5D (mean [SD] 66.7 [20] v 69.8 [22.2], P = 0.24); or health-related unemployment (% (N) 39 [26] v 25 [29.1], P = 0.61). After adjusting for confounders, living ≥50 km from the treating ICU was not associated with increased disability (odds ratio 0.61, 95% confidence interval: 0.33-1.16; P = 0.13) CONCLUSIONS: Survivors of intensive care in Victoria, Australia, who live at least 50 km from the treating ICU did not have greater disability than people living less than 50 km at 6 months after discharge. Living 50 km or more from the treating ICU was not associated with disability, nor was it associated with anxiety or depression, health status, or unemployment due to health.
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http://dx.doi.org/10.1016/j.aucc.2021.05.013DOI Listing
July 2021

Association between Net Ultrafiltration Rate and Renal Recovery among Critically Ill Adults with Acute Kidney Injury Receiving Continuous Renal Replacement Therapy: An Observational Cohort Study.

Blood Purif 2021 Jul 21:1-13. Epub 2021 Jul 21.

Department of Intensive Care Medicine, Austin Hospital, The University of Melbourne, Parkville, Victoria, Australia.

Introduction: Higher net ultrafiltration (UFNET) rates are associated with mortality among critically ill patients with acute kidney injury (AKI) and treated with continuous renal replacement therapy (CRRT).

Objective: The aim of the study was to discover whether UFNET rates are associated with renal recovery and independence from renal replacement therapy (RRT).

Methods: Retrospective cohort study using data from the Randomized Evaluation of Normal versus Augmented Level of Renal Replacement Therapy trial that enrolled 1,433 critically ill patients with AKI and treated with CRRT between December 2005 and November 2008 across 35 intensive care units in Australia and New Zealand. We examined the association between UFNET rate and time to independence from RRT by day 90 using competing risk regression after accounting for mortality. The UFNET rate was defined as the volume of fluid removed per hour adjusted for patient body weight.

Results And Conclusions: Median age was 67.3 (interquartile range [IQR], 57-76.3) years, 64.4% were male, median Acute Physiology and Chronic Health Evaluation-III score was 100 (IQR, 84-118), and 634 (44.2%) died by day 90. Kidney recovery occurred in 755 patients (52.7%). Using tertiles of UFNET rates, 3 groups were defined: high, >1.75; middle, 1.01-1.75; and low, <1.01 mL/kg/h. Proportion of patients alive and independent of RRT among the groups were 47.8 versus 57.2 versus 53.0%; p = 0.01. Using competing risk regression, higher UFNET rate tertile compared with middle (cause-specific hazard ratio [csHR], 0.79, 95% CI, 0.66-0.95; subdistribution hazard ratio [sHR], 0.80, 95% CI, 0.67-0.97) and lower (csHR, 0.69, 95% CI, 0.56-0.85; sHR, 0.78, 95% CI 0.64-0.95) tertiles were associated with a longer time to independence from RRT. Every 1.0 mL/kg/h increase in rate was associated with a lower probability of kidney recovery (csHR, 0.81, 95% CI, 0.74-0.89; and sHR, 0.87, 95% CI, 0.80-0.95). Using the joint model, longitudinal increases in UFNET rates were also associated with a lower renal recovery (β = -0.29, p < 0.001). UFNET rates >1.75 mL/kg/h compared with rates 1.01-1.75 and <1.01 mL/kg/h were associated with a longer duration of dependence on RRT. Randomized clinical trials are required to confirm this UFNET rate-outcome relationship.
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http://dx.doi.org/10.1159/000517281DOI Listing
July 2021

Personalized mechanical ventilation in acute respiratory distress syndrome.

Crit Care 2021 07 16;25(1):250. Epub 2021 Jul 16.

Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.

A personalized mechanical ventilation approach for patients with adult respiratory distress syndrome (ARDS) based on lung physiology and morphology, ARDS etiology, lung imaging, and biological phenotypes may improve ventilation practice and outcome. However, additional research is warranted before personalized mechanical ventilation strategies can be applied at the bedside. Ventilatory parameters should be titrated based on close monitoring of targeted physiologic variables and individualized goals. Although low tidal volume (V) is a standard of care, further individualization of V may necessitate the evaluation of lung volume reserve (e.g., inspiratory capacity). Low driving pressures provide a target for clinicians to adjust V and possibly to optimize positive end-expiratory pressure (PEEP), while maintaining plateau pressures below safety thresholds. Esophageal pressure monitoring allows estimation of transpulmonary pressure, but its use requires technical skill and correct physiologic interpretation for clinical application at the bedside. Mechanical power considers ventilatory parameters as a whole in the optimization of ventilation setting, but further studies are necessary to assess its clinical relevance. The identification of recruitability in patients with ARDS is essential to titrate and individualize PEEP. To define gas-exchange targets for individual patients, clinicians should consider issues related to oxygen transport and dead space. In this review, we discuss the rationale for personalized approaches to mechanical ventilation for patients with ARDS, the role of lung imaging, phenotype identification, physiologically based individualized approaches to ventilation, and a future research agenda.
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http://dx.doi.org/10.1186/s13054-021-03686-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284184PMC
July 2021

A Randomized, Multicenter, Open-Label, Blinded End Point, Phase 2, Feasibility, Efficacy, and Safety Trial of Preoperative Microvascular Protection in Patients Undergoing Major Abdominal Surgery.

Anesth Analg 2021 Oct;133(4):1036-1047

Department of Critical Care, University of Melbourne, Melbourne, Australia.

Background: The endothelial glycocalyx, a carbohydrate-rich layer coating all endothelial surfaces, plays a fundamental role in the function of microcirculation. The primary aim of this study was to evaluate the feasibility of using dexamethasone and albumin to protect the endothelial glycocalyx in patients undergoing abdominal surgery. Secondary and exploratory outcomes included efficacy and safety.

Methods: We conducted a multicenter, open-label, blinded end point, phase 2, randomized trial. Patients undergoing colorectal, pancreas, or liver surgery were recruited and randomized to receive either intravenous dexamethasone (16 mg) and 20% albumin (100 mL) at induction of anesthesia, then 200 mL of 20% albumin with each subsequent 1000 mL of crystalloid administered (dexamethasone and albumin [Dex-Alb] group), or crystalloid fluid only with no dexamethasone (control group). Feasibility end points included patient recruitment and retention, consent rate, and successful study drug administration. The primary efficacy end point was the measurement of plasma syndecan-1 level on postoperative day (POD) 1, and secondary end points were heparan sulfate levels and inflammatory markers measured at 4 perioperative timepoints. Safety end points included errors in administration of the intervention, hyperglycemia, occurrence of postoperative complications, and patient retention.

Results: Seventy-two patients were randomized. All feasibility end points were achievable. There were no statistically significant differences observed in median (interquartile range) syndecan-1 levels on POD 1 (39 ng·mL-1 [20-97] in the Dex-Alb group versus 41 ng·mL-1 [19-84] in the control group; difference in medians -2.1, 95% confidence interval [CI], -13 to 8.6; P = .69). The Dex-Alb group had lower POD 1 heparan sulfate levels (319 ng·mL-1 [161-717] in the Dex-Alb group versus 1422 [670-2430] ng·mL-1 in the control group; difference in medians -1085, 95% CI, -1779 to -391) and C-reactive protein (CRP) levels on POD 1 (48 [29-77] mg·L-1 in the Dex-Alb group versus 85 mg·L-1 [49-133] in the control group; difference in medians -48, 95% CI, -75 to -21). Fewer patients had one or more postoperative complication in the Dex-Alb group than in the control group (6 [17%] vs 18 patients [50%]; odds ratio = 0.2, 95% CI, 0.06-0.6).

Conclusions: Intravenous dexamethasone and albumin administration was feasible but did not reduce syndecan-1 on POD 1 in patients undergoing abdominal surgery. Given the clinically important CIs observed between the groups for heparan sulfate, CRP, and postoperative complications, a larger trial assessing the associations between dexamethasone and albumin administration and these outcomes is warranted.
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http://dx.doi.org/10.1213/ANE.0000000000005667DOI Listing
October 2021

Characteristics and Physiologic Changes After 4% Albumin Fluid Boluses in a PICU.

Pediatr Crit Care Med 2021 Jul 13. Epub 2021 Jul 13.

Pediatric Intensive Care Unit, Royal Children's Hospital, Melbourne, VIC, Australia. Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia. Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC, Australia. Department of Cardiac Surgery, Royal Children's Hospital, Melbourne, VIC, Australia. Decision Support Unit, Royal Children's Hospital, Melbourne, VIC, Australia. Data Analytics Research and Evaluation (DARE), Department of Critical Care, The University of Melbourne and The Austin Hospital, Melbourne, VIC, Australia. Department of Intensive Care, Royal Melbourne Hospital, Melbourne, VIC, Australia. Department of Intensive Care, Austin Hospital, Melbourne, VIC, Australia. Australian and New Zealand Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.

Objectives: To describe the characteristics, hemodynamic, and physiologic changes after 4% albumin fluid boluses in critically ill children.

Design: Retrospective observational study.

Setting: Single-center PICU.

Patients: Children in a cardiac and general PICU.

Interventions: None.

Measurements And Main Results: Between January 2017 and May 2019, there were 1,003 fluid boluses of 4% albumin during 420 of 5,731 admissions (7.8%), most commonly in children with congenital/acquired heart disease (71.2%) and sepsis (7.9%). The median fluid bolus dose was 10 mL/kg (interquartile range, 5.8-14.6 mL/kg), and its duration 30 minutes (interquartile range, 14.0-40.0 min; n = 223). After the fluid bolus, a significant change in mean arterial pressure (2.3 mm Hg [5.1%], 2.7 mm Hg [5.8%], 2.9 mm Hg [6.1%], and 3.8 mm Hg [8.0%] at 1, 2, 3, and 4 hr, respectively [p ≤ 0.001]) only occurred in children less than or equal to 12 months old. A mean arterial pressure response, defined by an increase greater than or equal to 10% from baseline, occurred in 290 of 887 patients (33%) with maximal response at 1 hour. Hypotension at baseline predicted the magnitude of mean arterial pressure increase at 60 (coefficient 24.3 [95% CI, 0.79-7.87]; p = 0.04) and 120 minutes (coefficient 26.1 [95% CI, 2.75-48.2]; p = 0.02). There were no biochemical or hematocrit changes within 4 hours of the fluid bolus. Urine output for the entire cohort was 2 mL/kg/hr at baseline and did not change with the fluid bolus.

Conclusions: Fluid boluses of 4% albumin were common and predominantly in children with cardiac disease and sepsis with a median dose of 10 mL/kg given over half an hour. Such treatment was associated with significant hemodynamic changes only in children less than 12 months old, and we failed to identify an association with urine output.
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July 2021

Trials of dexmedetomidine sedation in ventilated critically ill septic patients: Challenges, limitations and opportunities.

Anaesth Crit Care Pain Med 2021 08 2;40(4):100925. Epub 2021 Jul 2.

Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia; Department of Intensive Care, Austin Hospital, Melbourne, Australia; Department of Critical Care, The University of Melbourne, Melbourne, Australia; Department of Intensive Care, Royal Melbourne Hospital, Melbourne, Australia.

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http://dx.doi.org/10.1016/j.accpm.2021.100925DOI Listing
August 2021

Early Resuscitation in Paediatric Sepsis Using Inotropes - A Randomised Controlled Pilot Study in the Emergency Department (RESPOND ED): Study Protocol and Analysis Plan.

Front Pediatr 2021 31;9:663028. Epub 2021 May 31.

Child Health Research Centre, The University of Queensland, and Paediatric Intensive Care Unit, Queensland Children's Hospital, Brisbane, QLD, Australia.

Septic shock in children still carries substantial mortality and morbidity. While resuscitation with 40-60 mL/kg intravenous fluid boluses remains a cornerstone of initial resuscitation, an increasing body of evidence indicates potential for harm related to high volume fluid administration. We hypothesize that a protocol on early use of inotropes in children with septic shock is feasible and will lead to less fluid bolus use compared to standard fluid resuscitation. Here, we describe the protocol of the Early Resuscitation in Paediatric Sepsis Using Inotropes - A Randomised Controlled Pilot Study in the Emergency Department (RESPOND ED). The RESPOND ED study is an open label randomised controlled, two arm, multicentre pilot study conducted at four specialised paediatric Emergency Departments. Forty children aged between 28 days and 18 years treated for presumed septic shock will be randomized in a 1:1 ratio to early inotropes vs. standard fluid resuscitation. Early inotrope treatment is defined as the commencement of a continuous intravenous adrenaline infusion after 20 mL/kg fluid bolus resuscitation. Standard fluid resuscitation is defined as delivery of 40 to 60 mL/kg fluid bolus resuscitation prior to commencement of inotropes. In addition to feasibility outcomes, survival free of organ dysfunction censored at 28 days will be assessed as the main clinical outcome. The study cohort will be followed up at 28 days, and at 6 months post enrolment to assess quality of life and functional status. Biobanking nested in the study cohort will be performed to enable ancillary biomarker studies. The trial has ethical clearance (Children's Health Queensland, Brisbane, HREC/18/QCHQ/49168) and is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12619000828123). Enrolment commenced on July 21st, 2019. The primary manuscript will be submitted for publication in a peer-reviewed journal. Australian and New Zealand Clinical Trials Registry, ACTRN12619000828123.
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http://dx.doi.org/10.3389/fped.2021.663028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200662PMC
May 2021

Dysnatremia and 6-Month Functional Outcomes in Critically Ill Patients With Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study.

Crit Care Explor 2021 Jun 8;3(6):e0445. Epub 2021 Jun 8.

The Alfred Hospital, Melbourne, VIC, Australia.

Objectives: To investigate the association between plasma sodium concentrations and 6-month neurologic outcome in critically ill patients with aneurysmal subarachnoid hemorrhage.

Design: Prospective cohort study.

Setting: Eleven ICUs in Australia and New Zealand.

Participants: Three-hundred fifty-six aneurysmal subarachnoid hemorrhage patients admitted to ICU between March 2016 and June 2018. The exposure variable was daily measured plasma sodium.

Interventions: None.

Measurements And Main Results: Six-month neurologic outcome as measured by the modified Rankin Scale. A poor outcome was defined as a modified Rankin Scale greater than or equal to 4. The mean age was 57 years (± 12.6 yr), 68% were female, and 32% ( = 113) had a poor outcome. In multivariable analysis, including age, illness severity, and process of care measures as covariates, higher mean sodium concentrations (odds ratio, 1.17; 95% CI, 1.05-1.29), and greater overall variability-as measured by the sd (odds ratio, 1.53; 95% CI, 1.17-1.99)-were associated with a greater likelihood of a poor outcome. Multivariable generalized additive modeling demonstrated, specifically, that a high initial sodium concentration, followed by a gradual decline from day 3 onwards, was also associated with a poor outcome. Finally, greater variability in sodium concentrations was associated with a longer ICU and hospital length of stay: mean ICU length of stay ratio (1.13; 95% CI, 1.07-1.20) and mean hospital length of stay ratio (1.08; 95% CI, 1.01-1.15).

Conclusions: In critically ill aneurysmal subarachnoid hemorrhage patients, higher mean sodium concentrations and greater variability were associated with worse neurologic outcomes at 6 months, despite adjustment for known confounders. Interventional studies would be required to demonstrate a causal relationship.
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http://dx.doi.org/10.1097/CCE.0000000000000445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189636PMC
June 2021

Sex differences in illness severity and mortality among adult intensive care patients: A systematic review and meta-analysis.

J Crit Care 2021 Oct 4;65:116-123. Epub 2021 Jun 4.

Department of Intensive Care, Austin Health, Melbourne, VIC, Australia; Centre for Integrated Critical Care, University of Melbourne, Melbourne, VIC, Australia; Australia and New Zealand Intensive Care Research Centre, School of Public Health and Preventative Medicine, Monash University, Melbourne, VIC, Australia; Department of Intensive Care, Royal Melbourne Hospital, Melbourne, VIC, Australia.

Purpose: To investigate the association between sex and illness severity and mortality of ICU patients.

Methods: We performed systematic searches of MEDLINE and EMBASE for observational studies of adult ICU patients that explicitly examined the association between sex and illness severity or mortality. We used a random effects model to calculate standardised mean differences in illness severity scores and pooled odds ratios for mortality of women compared to men.

Results: We identified 21 studies with 505,138 participants in total (43.1% women). There was substantial heterogeneity among studies. Only two studies were at low risk of bias overall. At ICU admission, there was a pattern of higher illness severity scores among women (standardised mean difference 0.04, 95% CI -0.01-0.09). Women had higher risk-adjusted mortality than men at ICU discharge (OR 1.25 95% CI 1.03-1.50) and 1 year (OR 1.08, 95% CI 1.02-1.13), however this finding was not robust to sensitivity analysis.

Conclusions: Women tend to have higher illness severity scores at ICU admission. Women also appear to have higher risk-adjusted mortality than men at ICU discharge and at 1 year. Given the heterogeneity and risk of bias in the existing literature, additional studies are needed to confirm or refute these findings.
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http://dx.doi.org/10.1016/j.jcrc.2021.05.019DOI Listing
October 2021

Immunosuppressive strategies in invasively ventilated ARDS COVID-19 patients.

Minerva Anestesiol 2021 08 8;87(8):891-902. Epub 2021 Jun 8.

Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy.

Background: COVID-19 is associated with elevated levels of inflammatory cytokines. We present the characteristics and outcomes of patients treated in the Intensive Care Unit (ICU) with immunosuppressive drugs, either tocilizumab or anakinra compared with controls.

Methods: A single-center observational prospective study on ICU invasively ventilated COVID-19 patients. The primary outcome was the clinical improvement at day 28. A Bayesian framework was employed, and all analyses were adjusted for confounders.

Results: Sixty-one consecutive invasively ventilated patients were included, nine (14.7%) received tocilizumab and 15 (24.6%) received anakinra. Over the first seven days, tocilizumab was associated with a greater decrease in C-reactive protein (P<0.001). After adjusting for confounders, the probability of clinical improvement at day 28 compared to control was 7∙6% (OR=0.36 [95% CrI: 0.09-1.46]) for tocilizumab and 40.9% (OR=0.89 [95% CrI: 0.32-2.43]) for anakinra. At day 28, the probability of being in a better clinical category was 2.5% (OR=2.98 [95% CrI: 1.00-8.88]) for tocilizumab, and 49.5% (OR=1.00 [95% CrI: 0.42-2.42]) for anakinra.

Conclusions: In invasively ventilated COVID-19 patients, treatment with anakinra was associated with a higher probability of clinical improvement compared to tocilizumab; however, treatment with either drug did not result in clinically meaningful improvements compared with controls.
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http://dx.doi.org/10.23736/S0375-9393.21.15339-8DOI Listing
August 2021
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