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Objectives: To describe haemodynamic resuscitation practices in ED patients with suspected sepsis and hypotension. Methods: This was a prospective, multicentre, observational study conducted in 70 hospitals in Australia and New Zealand between September 2018 and January 2019. Consecutive adults presenting to the ED during a 30‐day period at each site, with suspected sepsis and hypotension (systolic blood pressure <100 mmHg) despite at least 1000 mL fluid resuscitation, were eligible. Data included baseline demographics, clinical and laboratory variables and intravenous fluid volume administered, vasopressor administration at baseline and 6‐ and 24‐h post‐enrolment, time to antimicrobial administration, intensive care admission, organ support and in‐hospital mortality. Results: A total of 4477 patients were screened and 591 were included with a mean (standard deviation) age of 62 (19) years, Acute Physiology and Chronic Health Evaluation II score 15.2 (6.6) and a median (interquartile range) systolic blood pressure of 94 mmHg (87–100). Median time to first intravenous antimicrobials was 77 min (42–148). A vasopressor infusion was commenced within 24 h in 177 (30.2%) patients, with noradrenaline the most frequently used (n = 138, 78%). A median of 2000 mL (1500–3000) of intravenous fluids was administered prior to commencing vasopressors. The total volume of fluid administered from pre‐enrolment to 24 h was 4200 mL (3000–5661), with a range from 1000 to 12 200 mL. Two hundred and eighteen patients (37.1%) were admitted to an intensive care unit. Overall in‐hospital mortality was 6.2% (95% confidence interval 4.4–8.5%). Conclusion: Current resuscitation practice in patients with sepsis and hypotension varies widely and occupies the spectrum between a restricted volume/earlier vasopressor and liberal fluid/later vasopressor strategy. [ABSTRACT FROM AUTHOR]

Objective: There is uncertainty about the optimal i.v. fluid volume and timing of vasopressor commencement in the resuscitation of patients with sepsis and hypotension. We aim to study current resuscitation practices in EDs in Australia and New Zealand (the Australasian Resuscitation In Sepsis Evaluation: FLUid or vasopressors In Emergency Department Sepsis [ARISE FLUIDS] observational study). Methods: ARISE FLUIDS is a prospective, multicentre observational study in 71 hospitals in Australia and New Zealand. It will include adult patients presenting to the ED during a 30 day period with suspected sepsis and hypotension (systolic blood pressure <100 mmHg) despite at least 1000 mL fluid resuscitation. We will obtain data on baseline demographics, clinical and laboratory variables, all i.v. fluid given in the first 24 h, vasopressor use, time to antimicrobial administration, admission to intensive care, organ failure and in‐hospital mortality. We will specifically describe (i) the volume of fluid administered at the following time points: when meeting eligibility criteria, in the first 6 h, at 24 h and prior to vasopressor commencement and (ii) the frequency and timing of vasopressor use in the first 6 h and at 24 h. Screening logs will provide reliable estimates of the proportion of ED patients meeting eligibility criteria for a subsequent randomised controlled trial. Discussion: This multicentre, observational study will provide insight into current haemodynamic resuscitation practices in patients with sepsis and hypotension as well as estimates of practice variation and patient outcomes. The results will inform the design and feasibility of a multicentre phase III trial of early haemodynamic resuscitation in patients presenting to ED with sepsis and hypotension. [ABSTRACT FROM AUTHOR]

Purpose: The Sepsis-3 consensus task force defined sepsis as life-threatening organ dysfunction caused by dysregulated host response to infection. However, the clinical criteria for this definition were neither designed for nor validated in children. We validated the performance of SIRS, age-adapted SOFA, quick SOFA and PELOD-2 scores as predictors of outcome in children.Methods: We performed a multicentre binational cohort study of patients < 18 years admitted with infection to ICUs in Australia and New Zealand. The primary outcome was ICU mortality. SIRS, age-adapted SOFA, quick SOFA and PELOD-2 scores were compared using crude and adjusted area under the receiver operating characteristic curve (AUROC) analysis.Results: Of 2594 paediatric ICU admissions due to infection, 151 (5.8%) children died, and 949/2594 (36.6%) patients died or experienced an ICU length of stay ≥ 3 days. A ≥ 2-point increase in the individual score was associated with a crude mortality increase from 3.1 to 6.8% for SIRS, from 1.9 to 7.6% for age-adapted SOFA, from 1.7 to 7.3% for PELOD-2, and from 3.9 to 8.1% for qSOFA (p < 0.001). The discrimination of outcomes was significantly higher for SOFA (adjusted AUROC 0.829; 0.791-0.868) and PELOD-2 (0.816; 0.777-0.854) than for qSOFA (0.739; 0.695-0.784) and SIRS (0.710; 0.664-0.756).Conclusions: SIRS criteria lack specificity to identify children with infection at substantially higher risk of mortality. We demonstrate that adapting Sepsis-3 to age-specific criteria performs better than Sepsis-2-based criteria. Our findings support the translation of Sepsis-3 into paediatric-specific sepsis definitions and highlight the importance of robust paediatric organ dysfunction characterization. [ABSTRACT FROM AUTHOR]

The authors highlight the side effects of hydroxyethyl starch (HES), an artificial colloid solution used in treating hypovolemia. Topics covered include link of HES in the increased risk of acute kidney injury (AKI), trials showing increased risk of bleeding with the use of HES as compared with crystalloid solutions in patients with sepsis, and increased mortality with HES in critically ill patients.

Purpose: This study aimed to compare the biochemical effects of Phoxilium (containing phosphate at 1.2 mmol/L; Gambro Lundia AB, Lund, Sweden) and Hemosol-B0 (Gambro Lundia AB) as dialysate and/or replacement fluid during continuous renal replacement therapy (CRRT). Methods: We examined serum biochemistry in critically ill patients for 42 hours of Phoxilium administration for the prevention of hypophosphatemia during CRRT and compared them with corresponding results in random historical controls who received Hemosol-B0. Results: We studied 15 patients in each arm (Phoxilium vs Hemosol-B0). Respective median ages were 57 (49-68) and 64 (57-67) years. Baseline patient illness severity scores, prescribed CRRT effluent rates, and cumulative phosphate intakes were comparable. After 36 to 42 hours of Phoxilium administration, serum phosphate levels increased from 0.95 (0.81-1.13) to 1.44 (1.23-1.78) mmol/L, in contrast to the decline from 1.71 (1.09-2.00) to 0.83 (0.55-1.59) mmol/L with Hemosol-B0 (P = .0001). Serum ionized calcium levels decreased from 1.27 (1.22-1.37) to 1.12 (1.06-1.21) mmol/L with Phoxilium, compared with an increase from 1.09 (0.90-1.19) to 1.20 (1.16-1.25) mmol/L with Hemosol-B0 (P b .0001). Serum bicarbonate, base excess levels, and effective strong ion difference decreased with Phoxilium and were lower than those with Hemosol-B0 at 36 to 42 hours (P b .05). Conclusion: Phoxilium effectively prevented hypophosphatemia during CRRT but was associated with relative metabolic acidosis and hypocalcemia compared with Hemosol-B0 use. [ABSTRACT FROM AUTHOR]

Purpose: Determine whether there are unique patterns to the urine biochemistry profile in septic compared with non-septic acute kidney injury (AKI) and whether urinary biochemistry predicts worsening AKI, need for renal replacement therapy and mortality. Materials and Methods: Prospective cohort study of critically ill patients with septic and non-septic AKI, defined by the RIFLE (Risk, Injury, Failure, Loss, End-Stage) criteria. Urine biochemistry parameters were compared between septic and non-septic AKI and were correlated with neutrophil gelatinaseassociated lipocalin (NGAL), worsening AKI, renal replacement therapy (RRT), and mortality. Results: Eighty-three patients were enrolled, 43 (51.8%) with sepsis. RIFLE classwas not different between groups (P = .43). Urine sodium (UNa) b 20 mmol/L, fractional excretion of sodium (FeNa) b1%, and fractional excretion of urea (FeU) b 35% were observed in 25.3%, 57.8%, and 33.7%, respectively. Septic AKI had lower UNa compared with non-septic AKI (P = .04). There were no differences in FeNa or FeU between groups. Urine NGALwas higher for FeNa.1%compared to FeNab1%(177.4 ng/mL [31.9-956.5] vs 48.0 ng/mL [21.1-232.4], P = .04). FeNa showed low correlation with urine NGAL (P = .05) and plasma NGAL (P = .14). There was poor correlation between FeU and urine NGAL (P =.70) or plasmaNGAL (P = .41). UNa, FeNa, and FeU showed poor discrimination for worsening AKI, RRT and mortality. Conclusion: Urine biochemical profiles do not discriminate septic and non-septicAKI. UNa, FeNa, and FeU do not reliably predict biomarker release, worsening AKI, RRT ormortality. These data imply limited utility for these measures in clinical practice in critically ill patients with AKI. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To describe the characteristics and outcomes of patients receiving a medical emergency team (MET) review for the MET syndromes of respiratory distress or hypotension and to assess the effect of delayed MET activation on their outcomes. Materials and Methods: We retrospectively analyzed the medical records of 2 cohorts of 100 patients for each of the MET syndromes of respiratory distress and hypotension. We collected information on patient demographics, comorbidities, presence of sepsis, and patient outcome. We documented the presence and duration of delayed MET activation. Results: Patients with respiratory distress were more likely to be postoperative (40% vs 28%, P = .07), but less likely to have a history of congestive cardiac failure (12% vs 22%, P = .06). Sepsis was present in 58% of cases. The hospital mortality for MET calls due to respiratory distress and hypotension was 38% and 35%, respectively (P = .77). Delayed MET calls occurred in 50% of patients with the MET syndrome of respiratory distress and in 39% of those with hypotension (P = .11). The median duration of delay was 12 hours in patients with respiratory distress compared to 5 hours for patients with hypotension (P = .016). A delay in making a MET call was associated with an increase in mortality (odds ratio, 2.10; 95% confidence interval, 1.01-4.34; P = .045). Conclusions: Patients receiving MET calls for respiratory distress or hypotension were elderly and had a mortality greater than 35%. In many cases, MET activation was delayed. This delay was associated with increased mortality. [Copyright &y& Elsevier]

Objective: To evaluate the effects of early short-term, isovolaemic haemofiltration at 45 ml/kg/h on physiological and clinical outcomes in patients with septic shock.Design: Retrospective study before and after a change of unit protocol (study period 8 years).Setting: Intensive care unit of metropolitan hospital.Patients: Eighty patients with septic shock.Interventions: Introduction of a new septic shock protocol based on early isovolaemic haemofiltration (EIHF). In the pre-EIHF period (before), 40 patients received conventional supportive therapy. In the post-EIHF period (after), 40 patients received EIHF at 45 ml/kg/h of plasma-water exchange over 6 h followed by conventional continuous venovenous haemofiltration (CVVH). Anticoagulation policy remained unchanged.Measurements and Main Results: The two groups were comparable for age, gender and baseline APACHE II score. Delivered haemofiltration dose was above 85% of prescription in all patients. PaO2/FiO2 ratio increased from 117+/-59 to 240+/-50 in EIHF, while it changed from 125+/-55 to 160+/-50 in the control group (p<0.05). In EIHF patients, mean arterial pressure increased (95+/-10 vs 60+/-12 mmHg; p<0.05), and norepinephrine dose decreased (0.20+/-2 vs 0.02+/-0.2 microg/kg/min; p<0.05). Among EIHF patients, 28 (70%) were successfully weaned from the ventilator compared with 15 (37%) in the control group (p<0.01). Similarly, 28-day survival was 55% compared with 27.5% (p<0.05). Length of stay in the ICU was 9+/-5 days compared with 16+/-4 days (p<0.002).Conclusions: In patients with septic shock, EIHF was associated with improved gas exchange, haemodynamics, greater likelihood of successful weaning and greater 28-day survival compared with conventional therapy. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Determine current resuscitation practices and outcomes in patients presenting to the emergency department (ED) with sepsis and hypoperfusion or septic shock in Australia and New Zealand (ANZ). Methods: Three-month prospective, multi-centre, observational study of all adult patients with sepsis and hypoperfusion or septic shock in the ED of 32 ANZ tertiary-referral, metropolitan and rural hospitals. Results: 324 patients were enrolled (mean [SD] age 63.4 [19.2] years, APACHE II score 19.0 [8.2], 52.5% male). Pneumonia (n =138/324, 42.6%) and urinary tract infection (n =98/324, 30.2%) were the commonest sources of sepsis. Between ED presentation and 6hours post-enrolment (T6hrs), 44.4% (n =144/324) of patients received an intra-arterial catheter, 37% (n =120/324) a central venous catheter and 0% (n =0/324) a continuous central venous oxygen saturation (ScvO2) catheter. Between enrolment and T6hrs, 32.1% (n =104/324) received a vasopressor infusion, 7.4% (n =24/324) a red blood cell transfusion, 2.5% (n =8/324) a dobutamine infusion and 18.5% (n =60/324) invasive mechanical ventilation. Twenty patients (6.2%) were transferred from ED directly to the operating theatre, 36.4% (n =118/324) were admitted directly to ICU, 1.2% (n =4/324) died in the ED and 56.2% (n =182/324) were transferred to the hospital floor. Overall ICU admission rate was 52.4% (n =170/324). ICU and overall in-hospital mortality were 18.8% (n =32/170) and 23.1% (n =75/324) respectively. In-hospital mortality was not different between patients admitted to ICU (24.7%, n =42/170) and the hospital floor (21.4%, n =33/154). Conclusions: Management of ANZ patients presenting to ED with sepsis does not routinely include protocolised, ScvO2-directed resuscitation. In-hospital mortality compares favourably with reported mortality in international sepsis trials and nationwide surveys of resuscitation practices. [Copyright &y& Elsevier]

Objectives: Angiotensin II is an emerging therapy for septic acute kidney injury, but it is unknown if its vasoconstrictor action induces renal hypoxia. We therefore examined the effects of angiotensin II on intrarenal PO2 in ovine sepsis. We also assessed the validity of urinary PO2 as a surrogate measure of medullary PO2.Design: Interventional study.Setting: Research Institute.Subjects: Sixteen adult Merino ewes (n = 8/group).Interventions: Sheep were instrumented with fiber-optic probes in the renal cortex, medulla, and within a bladder catheter to measure PO2. Conscious sheep were infused with Escherichia coli for 32 hours. At 24-30 hours, angiotensin II (0.5-33.0 ng/kg/min) or saline vehicle was infused.Measurements and Main Results: Septic acute kidney injury was characterized by hypotension and a 60% ± 6% decrease in creatinine clearance. During sepsis, medullary PO2 decreased from 36 ± 1 to 30 ± 3 mm Hg after 1 hour and to 20 ± 2 mm Hg after 24 hours; at these times, urinary PO2 was 42 ± 2, 34 ± 2, and 23 ± 2 mm Hg. Increases in urinary neutrophil gelatinase-associated lipocalin (12% ± 3%) and serum creatinine (60% ± 23%) were only detected at 8 and 24 hours, respectively. IV infusion of angiotensin II, at 24 hours of sepsis, restored arterial pressure and improved creatinine clearance, while not exacerbating medullary or urinary hypoxia.Conclusions: In septic acute kidney injury, renal medullary and urinary hypoxia developed several hours before increases in currently used biomarkers. Angiotensin II transiently improved renal function without worsening medullary hypoxia. In septic acute kidney injury, angiotensin II appears to be a safe, effective therapy, and urinary PO2 may be used to detect medullary hypoxia. [ABSTRACT FROM AUTHOR]

Aim: A new definition of sepsis released by an international task-force has introduced the concept of quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA). This study aimed to measure the proportion of patients who fulfilled qSOFA criteria during a Rapid Response Team (RRT) review and to assess their associated outcomes.Methods: We conducted a prospective study of adult RRT reviews over a one month period between 6th June and 10th July 2016 in a large tertiary hospital in Melbourne Australia RESULTS: Over a one-month period, there were 282 RRT reviews, 258 of which were included. One hundred out of 258 (38.8%) RRT review patients fulfilled qSOFA criteria. qSOFA positive patients were more likely to be admitted to the intensive care unit (29% vs 18%, P=0.04), to have repeat RRT reviews (27% vs 13%; p=0.007) and die in hospital (31% vs 10%, P<0.001). qSOFA positive patients with suspected infection were more likely to be admitted to the intensive care unit compared to patients with infection alone (37% vs 15%, P=0.002). Eleven of 42 patients (26%) who had infection and qSOFA died whilst in hospital, compared to 8/55 (15%) of patients with infection alone (P=0.2).Conclusion: Adult patients who are qSOFA positive at the time of their RRT review are at increased risk of in-hospital mortality. The assessment of qSOFA may be a useful triage tool during a RRT review. [ABSTRACT FROM AUTHOR]

Background & Aims Few studies have described the outcomes of patients with cirrhosis receiving intensive care unit (ICU) admission at a population level. We aimed to describe trends in the mortality of such patients in Australia and New Zealand (ANZ), and to investigate the relationship with associated organ failures. Methods We studied patients admitted to 172 ICUs on a non-elective basis, with and without cirrhosis between January 1st 2000 and December 31st 2015, as recorded by the ANZ Intensive Care Society Centre for Outcome and Resource Evaluation Adult Patient Database. We assessed severity of illness on admission using organ failure models and acute physiology scores. The primary outcome was hospital mortality. Results Patients with cirrhosis accounted for 17,044 of 776,873 non-elective ICU admissions (2.2%). Cirrhosis hospital mortality was 32.4% compared to 16.9% in the non-cirrhotic group ( p <0.0001). After adjustment for key confounders, cirrhosis had an independent effect on mortality with an odds ratio (OR) of 1.10 (1.06–1.15). There was no difference in the adjusted annual decline in mortality between patients with or without cirrhosis (OR 0.96 [0.95–0.97] vs. 0.96 [0.96–0.96], p = 0.67). No difference was seen in the adjusted decline in mortality of patients with cirrhosis when stratified by mechanical ventilation ( p = 0.92), liver transplant centre status ( p = 0.27) or presence of sepsis ( p = 0.09). Mortality increased with number of organ failures, however, the presence of cirrhosis was not found to affect this relationship ( p = 0.33). Conclusions The mortality of patients with cirrhosis admitted to ICU on a non-elective basis has declined significantly over time, comparable to patients without cirrhosis, and is predominantly governed by the number of organ failures. Outcomes are similar between non-liver transplant ICUs and liver transplant centres. Lay summary The outcomes of patients with liver cirrhosis admitted to intensive care units (ICUs) have been previously regarded as poor. We have demonstrated that in Australia and New Zealand, annual in-hospital death rates following ICU admission in this patient group are lower than previously reported, have improved over 16 years to 29% and are at a rate similar to patients without cirrhosis. Our data justify recommendations that advocate better access to intensive care for patients with cirrhosis. [ABSTRACT FROM AUTHOR]

Augmented renal clearance (ARC) is known to influence β-lactam antibiotic pharmacokinetics. This substudy of the BLING-II trial aimed to explore the association between ARC and patient outcomes in a large randomised clinical trial. BLING-II enrolled 432 participants with severe sepsis randomised to receive β-lactam therapy by continuous or intermittent infusion. An 8-h creatinine clearance (CL Cr ) measured on Day 1 was used to identify ARC, defined as CL Cr  ≥ 130 mL/min. Patients receiving any form of renal replacement therapy were excluded. Primary outcome was alive ICU-free days at Day 28. Secondary outcomes included 90-day mortality and clinical cure at 14 days following antibiotic cessation. A total of 254 patients were included, among which 45 (17.7%) manifested ARC [median (IQR) CL Cr 165 (144–198) mL/min]. ARC patients were younger ( P  <   0.001), more commonly male ( P  = 0.04) and had less organ dysfunction ( P  <   0.001). There was no difference in ICU-free days at Day 28 [ARC, 21 (12–24) days; no ARC, 21 (11–25) days; P  = 0.89], although clinical cure was significantly greater in the unadjusted analysis in those manifesting ARC [33/45 (73.3%) vs. 115/209 (55.0%) P  = 0.02]. This was attenuated in the multivariable analysis. No difference was noted in 90-day mortality. There were no statistically significant differences in clinical outcomes in ARC patients according to the dosing strategy employed. In this substudy of a large clinical trial of β-lactam antibiotics in severe sepsis, ARC was not associated with any differences in outcomes, regardless of dosing strategy. [ABSTRACT FROM AUTHOR]

The article discusses a study which measured renal blood flow in septic patients with acute kidney injury using cine phase-contrast magnetic resonance imaging. Results show that there was no rank correlation between renal blood flow index and creatinine clearance in patients with septic acute kidney injury. It concluded that cine phase-contrast magnetic resonance imaging can be used to noninvasively and safely assess renal perfusion in critically ill patients.