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Objective: We tested the hypothesis that responses to physiologic deterioration in hospital ward patients delayed by more than 15 minutes are associated with increased mortality.Design, Setting, and Participants: We used data from a 23-hospital cluster randomized trial (January 2004 to December 2004) of implementation of rapid response teams (intervention) versus standard practice with conventional cardiac arrest team-based responses to emergencies (control). We examined emergency calls in all hospitals. In intervention hospitals, we also examined such calls in the period before, during the introduction, and after the full implementation of a rapid response system. We studied the statistical association between such delayed calls and mortality.Main Outcomes and Measures: Hospital outcomes (mortality, unplanned ICU admissions, and cardiac arrests).Results: There were 3,135 emergency team calls in all hospitals. Overall, almost one third of such calls were delayed. In intervention hospitals, the proportion of delayed calls was similar before and after implementation of rapid response teams. Compared with control hospitals, in intervention hospitals, there was a significant decrease in the proportion of delayed calls during both the introduction (27.3% vs 34.3% weekly rate; incidence rate ratio, 0.84; p = 0.001) and the full implementation period (29.0% vs 34.5% weekly rate; incidence rate ratio, 0.84; p = 0.023). Delayed calls more likely occurred at night, in high dependence or coronary care units, in patients older than 75 years, in those with a decrease in Glasgow Coma Scale, or in those with hypotension as the reason for the call. Finally, in all hospitals, delayed calls were associated with an increased risk of unplanned ICU admissions (adjusted odds ratio = 1.56; 95% CI, 1.23-2.04; p ≤ 0.001) and death (adjusted odds ratio = 1.79; 95% CI, 1.43-2.27; p < 0.001).Conclusions: Among ward patients, emergency team activation in response to acute deterioration triggered more than 15 minutes after detection and documentation of instability is independently associated with an increased risk of ICU admission and death. [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.

Objectives: To explore the relationship between timing of continuous renal replacement therapy commencement and clinical outcomes in critically ill patients with acute kidney injury. The primary outcomes were all-cause mortality at 28 and 90 days. Design: Nested observational cohort study using data from the Randomized Evaluation of Normal Versus Augmented Level Replacement Therapy Study. Setting: Twenty-three ICUs in Australia and New Zealand. Patients: Four hundred thirty-nine critically ill patients with acute kidney injury Risk, Injury, Failure, Loss, End-stage kidney disease-injury (RIFLE-I) criteria. Interventions: None. Measurements and Main Results: The time between RIFLE-I acute kidney injury and randomization in the Randomized Evaluation of Normal Versus Augmented Level Replacement Therapy Study (proxy for continuous renal replacement therapy commencement) was the variable of interest. All baseline variables in the Randomized Evaluation of Normal Versus Augmented Level Replacement Therapy Study were assessed. Multivariable Cox, logistic, and linear regression models were used to assess the independent relationship of time of onset of RIFLE-I acute kidney injury and randomization and patient outcomes. The median time between RIFLE-I acute kidney injury and continuous renal replacement therapy commencement was 17.6 hours (interquartile range, 7.1-46 hr). Based on four groups of continuous renal replacement therapy commencement ([group 1; reference]: <7.1, [group 2]: ⩾ 7.1 to < 17.6, [group 3]: ⩾ 17.6 to < 46.0, [group 4]: ⩾ 46.0hr), earlier commencement of continuous renal replacement therapy was not associated with a significantly lower risk of death at 28 days (hazard ratio for group 2: 1.06, 95% Cl: 0.62-1.81; p = 0.83; hazard ratio for group 3: 1.23, 95% Cl: 0.71-2.12; p = 0.46; hazard ratio for group 4: 1.33, 95% Cl: 0.77- 2.31 ;p = 0.31). Similar findings were observed for death at 90 days. Conclusions: In a subgroup of participants of the Randomized Evaluation of Normal Versus Augmented Level Replacement Therapy Study, earlier commencement of continuous renal replacement therapy relative to RIFLE-I acute kidney injury was not significantly associated with improved survival. Additional studies with larger sample sizes and broader commencement times are warranted. [ABSTRACT FROM AUTHOR]

The article reports on a study of the value of novel and conventional serum biomarkers in predicting acute kidney injury (AKI) among adult cardiac surgical patients. It examined concentrations of plasma neutrophil gelatinase-associated lipocalin (NGAL) serum cystatin C, creatinine, and urea of 100 cardiac surgical patients. It showed that plasma NGAL and serum cystatin C were conventional biomarkers which are good in identifying patients who developed AKI after cardiac surgery.

The article offers information on extracorporeal therapy. It states that this kind of therapy has expanded over the past years from solely artificial renal replacement therapy. It also forwards that it is crucial to provide multiple organ support therapy to patients with multiple organ dysfunction syndrome. Nanotechnology has also changed the way therapy is delivered to patients with kidney ailments.

The renin-angiotensin system (RAS) constitutes one of the principal mechanisms to maintain hemodynamic and fluid homeostasis. However, most research until now on RAS primarily focuses on its relationship with hypertension and its role in critically ill hypotensive populations is not well understood. With the approval of angiotensin II (Ang II) in the United States and Europe, following a phase 3 randomized controlled trial showing efficacy in catecholamine-resistant vasodilatory shock, there is growing interest in RAS in critically ill patients. Among the fundamental components of RAS, renin acts as the initial stimulus for the entire system. In the context of hypotension, its release increases in response to low blood pressure sensed by renal baroreceptors and attenuated negative Ang II feedback loop. Thus, elevated renin could reflect disease severity and predict poor outcomes. Studies investigating this hypothesis have validated the prognostic accuracy of renin in various critically ill populations, with several reports indicating its superiority to lactate for mortality prediction. Accordingly, renin reduction has been used to assess the effectiveness of Ang II administration. Furthermore, renin holds potential to identify patients who might benefit from Ang II treatment, potentially paving the way for personalized vasopressor management. Despite these promising data, most available evidence is derived from retrospective analysis and necessitates prospective confirmation. The absence of a rapid, point-of-care and reliable renin assay presents another hurdle to its integration into routine clinical practice. This narrative review aims to describe the current understanding and future directions of renin as a biomarker during resuscitation of critically ill patients. [ABSTRACT FROM AUTHOR]

Patient sex affects treatment and outcomes in critical illness. Previous studies of sex differences in critical illness compared female and male patients. In this study, we describe the group of patients classified as a third sex admitted to ICUs in Australia and New Zealand. What are the admission characteristics and outcomes of ICU patients classified as belonging to a third sex group compared with patients classified as female or male? Retrospective observational study of admissions to 200 ICUs, recorded in the Australian and New Zealand Intensive Care Society's Adult Patient Database from 2018 to 2022. We undertook mixed effect logistic regression to compare hospital mortality across the sex groups, adjusted for illness severity, diagnosis, treatment limitation, year, and hospital. We examined 892,161 admissions, of whom 525 (0.06%) were classified as third sex. Patients classified as third sex were represented across all diagnostic categories, jurisdictions, and hospital types. On average, they were younger than the groups classified as female (59.2 ± 20.0 vs 61.3 ± 18.4 years; P =.02) or male (63.2 ± 16.7 years; P <.001), respectively. Patients classified as third sex were more likely to be admitted after orthopedic surgery (10.1% third sex admissions [95% CI, 7.7%-13.0%]; 6.2% female [95% CI, 6.1%-6.3%]; 4.8% male [95% CI, 4.7%-4.9%]) and drug overdose (8.8% third sex admissions [95% CI, 6.5%-11.5%]; 4.2% female [95% CI, 4.1%-4.2%]; 3.1% male [95% CI, 3.0%-3.1%]). There was no difference in the adjusted hospital mortality of patients classified as third sex compared with the other groups. Patients classified as third sex composed a small minority group of adult ICU patients. This group had a different diagnostic case mix but similar outcomes to the groups classified as female or male. Further characterizing a third sex group will require improved processes for recording sex and gender in health records. [Display omitted] [ABSTRACT FROM AUTHOR]

The issue of organ donation and of how the donor pool can or should be increased is one with significant practical, ethical and logistic implications. Here we comment on an article advocating a paradigm change in the so-called "dead donor rule". Such change would involve the societal and legal abandonment of the above rule and the introduction of mandated choice. In this commentary, we review some of the problems associated with the proposed changes as well as the problems associated with the current model. We emphasize the continuing problems with the definition of death and the physiological process of dying; we discuss the difficulties associated with a dichotomous view of death; we review the difficulties with non-beating heart donation and emphasize the current limitations of society's understanding of these complex issues. We conclude that public education remains the best approach and that such education should not be merely promotion of a particular ideology but honest debate of what is socially and morally acceptable and appropriate given the changes in vital organ support technology and the need to respect patient autonomy. [ABSTRACT FROM AUTHOR]

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

Objective: The early prediction of hospital admission is important to ED patient management. Using available electronic data, we aimed to develop a predictive model for hospital admission. Methods: We analysed all presentations to the ED of a tertiary referral centre over 7 years. To our knowledge, our data set of nearly 600 000 presentations is the largest reported. Using demographic, clinical, socioeconomic, triage, vital signs, pathology data and keywords in electronic notes, we trained a machine learning (ML) model with presentations from 2015 to 2020 and evaluated it on a held‐out data set from 2021 to mid‐2022. We assessed electronic medical records (EMRs) data at patient arrival (baseline), 30, 60, 120 and 240 min after ED presentation. Results: The training data set included 424 354 data points and the validation data set 53 403. We developed and trained a binary classifier to predict inpatient admission. On a held‐out test data set of 121 258 data points, we predicted admission with 86% accuracy within 30 min of ED presentation with 94% discrimination. All models for different time points from ED presentation produced an area under the receiver operating characteristic curve (AUC) ≥0.93 for admission overall, with sensitivity/specificity/F1‐scores of 0.83/0.90/0.84 for any inpatient admission at 30 min after presentation and 0.81/0.92/0.84 at baseline. The models retained lower but still high AUC levels when separated for short stay units or inpatient admissions. Conclusion: We combined available electronic data and ML technology to achieve excellent predictive performance for subsequent hospital admission. Such prediction may assist with patient flow. [ABSTRACT FROM AUTHOR]

Background: Anticoagulation for subsegmental pulmonary embolism (SSPE) is controversial. Aim: To assess the impact of clinical context on anticoagulation and outcomes of SSPE. Methods: We electronically searched computed tomography pulmonary angiogram reports to identify SSPE. We extracted demographic, risk factor, investigations and outcome data from the electronic medical record. We stratified patients according to anticoagulation and no anticoagulation. Results: From 1 January 2017 to 31 December 2019, we identified 166 patients with SSPE in 5827 pulmonary angiogram reports. Of these, 123 (74%) received anticoagulation. Compared with non‐anticoagulated patients, such patients had a different clinical context: higher rates of previous venous thromboembolism (11% vs 0%; P = 0.019), more recent surgery (26% vs 9%; P = 0.015), more elevated serum D‐dimer (22% vs 5%; P = 0.004), more lung parenchymal abnormalities (76% vs 61%; P = 0.037) and were almost twice as likely to require inpatient care (76% vs 42%; P < 0.001). Such patients also had twice the all‐cause mortality at 1 year (32% vs 16%). Conclusions: SSPE is diagnosed in almost 3% of pulmonary angiograms and is associated with high mortality, regardless of anticoagulation, due to coexistent disease processes rather than SSPE. Anticoagulation appears dominant but markedly affected by the clinical context of risk factors, alternative indications and illness severity. Thus, the controversy is partly artificial because anticoagulation after SSPE is clinically contextual with SSPE as only one of several factors. [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]

Background: We recently reported the results for a large randomized controlled trial of low tidal volume ventilation (LTVV) versus conventional tidal volume (CTVV) during major surgery when positive end expiratory pressure (PEEP) was equal between groups. We found no difference in postoperative pulmonary complications (PPCs) in patients who received LTVV. However, in the subgroup of patients undergoing laparoscopic surgery, LTVV was associated with a numerically lower rate of PPCs after surgery. We aimed to further assess the relationship between LTVV versus CTVV during laparoscopic surgery. Methods: We conducted a post-hoc analysis of this pre-specified subgroup. All patients received volume-controlled ventilation with an applied PEEP of 5 cmH2O and either LTVV (6 mL/kg predicted body weight [PBW]) or CTVV (10 mL/kg PBW). The primary outcome was the incidence of a composite of PPCs within seven days. Results: Three hundred twenty-eight patients (27.2%) underwent laparoscopic surgeries, with 158 (48.2%) randomised to LTVV. Fifty two of 157 patients (33.1%) assigned to LTVV and 72 of 169 (42.6%) assigned to conventional tidal volume developed PPCs within 7 days (unadjusted absolute difference, − 9.48 [95% CI, − 19.86 to 1.05]; p = 0.076). After adjusting for pre-specified confounders, the LTVV group had a lower incidence of the primary outcome than patients receiving CTVV (adjusted absolute difference, − 10.36 [95% CI, − 20.52 to − 0.20]; p = 0.046). Conclusion: In this post-hoc analysis of a large, randomised trial of LTVV we found that during laparoscopic surgeries, LTVV was associated with a significantly reduced PPCs compared to CTVV when PEEP was applied equally between both groups. Trial registration: Australian and New Zealand Clinical Trials Registry no: 12614000790640. [ABSTRACT FROM AUTHOR]

Objective: The application of rapid, non‐operator‐dependent, non‐invasive cardiac output monitoring (COM) may provide early physiological information in ED patients with haemodynamic instability (HI). Our primary objective was to assess the feasibility of measuring pre‐intervention (baseline) cardiac index (CI) and associated haemodynamic parameters. Methods: We performed a prospective observational study of adults shortly after presentation to the ED of a large university hospital with tachycardia or hypotension or both. We applied non‐invasive COM for 5 min and recorded CI, mean arterial pressure (MAP), stroke volume index (SVI) and systemic vascular resistance index (SVRI). We assessed for differences between those presenting with hypotension or hypotension and tachycardia with tachycardia alone and between those with or without suspected infection. Results: We obtained haemodynamic parameters in 46 of 49 patients. In patients with hypotension or hypotension and tachycardia (n = 15) rather than tachycardia alone (n = 31), we observed a lower MAP (60.8 vs 87.7, P < 0.0001), CI (2.8 vs 3.9, P = 0.0167) and heart rate (85.5 vs 115.4, P < 0.0001). There was no difference in SVI (33.7 vs 33.4, P = 0.93) or SVRI (1970 vs 2088, P = 0.67). Patients with suspected infection had similar haemodynamic values except for a lower SVRI (1706 vs 2237, P = 0.011). Conclusions: Rapid, non‐operator‐dependent, non‐invasive COM was possible in >90% of ED patients presenting with HI. Compared with tachycardia alone, patients with hypotension had lower CI, MAP and heart rate, while those with suspected infection had a lower SVRI. This technology provides novel insights into the early state of the circulation in ED patients with HI. [ABSTRACT FROM AUTHOR]

Background: Optimal cerebral oxygenation is considered fundamental to cerebral protection in cardiac arrest (CA) patients. Hypercapnia increases cerebral blood flow and may also improve cerebral oxygenation. It is uncertain, however, whether this effect occurs in mechanically ventilated early survivors of CA.Methods: We enrolled mechanically ventilated resuscitated patients within 36h of their cardiac arrest. We performed a prospective double cross-over physiological study comparing the impact of normocapnia (PaCO2 35-45mmHg) vs. mild hypercapnia (PaCO2 45-55mmHg) on regional cerebral tissue oxygen saturation (SctO2) assessed by near infrared spectroscopy (NIRS).Results: We studied seven adult CA patients with a median time to return of spontaneous circulation of 28min at a median of 26h and 30min after CA. During normocapnia (median EtCO2 of 32mmHg [30-41mmHg] and PaCO2 of 37mmHg [32-45mmHg]) the median NIRS-derived left frontal SctO2 was 61% [52-65%] and the right frontal SctO2 was 61% [54-68%]. However, during mild hypercapnia (median EtCO2 of 49mmHg [40-57mmHg] and PaCO2 of 52mmHg [43-55mmHg) the median left frontal SctO2 increased to 69% [59-78%] and the right frontal SctO2 increased to 73% [61-76%])(p=0.001, for all comparisons).Conclusion: During the early post-resuscitation period, in mechanically ventilated CA patients, mild hypercapnia increases cerebral oxygenation as assessed by NIRS. Further investigations of the effect of prolonged mild hypercapnia on cerebral oxygenation and patient outcomes appear justified. [ABSTRACT FROM AUTHOR]

The article presents updates on the development of research and supportive care protocols for Ebola virus disease (EVD) patients as of January 2015. Topics discussed include the overall EVD case fatality rate in West Africa, characteristics of the disease, and treatment uncertainties that should be resolved. The authors suggest the need to deploy and evaluate specific supportive care for EVD patients.

Abstract: Background: Arterial carbon dioxide tension (PaCO2) affects neuronal function and cerebral blood flow. However, its association with outcome in patients admitted to intensive care unit (ICU) after cardiac arrest (CA) has not been evaluated. Methods and results: Observational cohort study using data from the Australian New Zealand (ANZ) Intensive Care Society Adult-Patient-Database (ANZICS-APD). Outcomes analyses were adjusted for illness severity, co-morbidities, hypothermia, treatment limitations, age, year of admission, glucose, source of admission, PaO2 and propensity score. We studied 16,542 consecutive patients admitted to 125 ANZ ICUs after CA between 2000 and 2011. Using the APD-PaCO2 (obtained within 24h of ICU admission), 3010 (18.2%) were classified into the hypo- (PaCO2 <35mmHg), 6705 (40.5%) into the normo- (35–45mmHg) and 6827 (41.3%) into the hypercapnia (>45mmHg) group. The hypocapnia group, compared with the normocapnia group, had a trend toward higher in-hospital mortality (OR 1.12 [95% CI 1.00–1.24, p =0.04]), lower rate of discharge home (OR 0.81 [0.70–0.94, p <0.01]) and higher likelihood of fulfilling composite adverse outcome of death and no discharge home (OR 1.23 [1.10–1.37, p <0.001]). In contrast, the hypercapnia group had similar in-hospital mortality (OR 1.06 [0.97–1.15, p =0.19]) but higher rate of discharge home among survivors (OR 1.16 [1.03–1.32, p =0.01]) and similar likelihood of fulfilling the composite outcome (OR 0.97 [0.89–1.06, p =0.52]). Cox-proportional hazards modelling supported these findings. Conclusions: Hypo- and hypercapnia are common after ICU admission post-CA. Compared with normocapnia, hypocapnia was independently associated with worse clinical outcomes and hypercapnia a greater likelihood of discharge home among survivors. [Copyright &y& Elsevier]

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]

Summary: Objective: To examine NFR orders in relation to adverse events and emergency team calls in hospitals with or without a Medical Emergency Team (MET) system during the MERIT study. Method: Within a cluster randomized controlled trial (the MERIT study), examining the effect of introducing a MET system, we recorded NFR orders in relation to adverse events and emergency team calls. We compared the proportion and rate of NFR orders issued in relation to “adverse events” and “adverse event-free emergency team calls” in hospitals with or without a MET system. Results: Information on NFR orders was available for 3650 patients who died, 1466 patients who had an unplanned ICU admission, 574 patients who suffered a cardiac arrest and 1529 patients who had a adverse event-free emergency team call. Close to 90% of deaths occurred in patients with a previously documented NFR order. Only approximately 4% of cardiac arrests had a previously documented NFR order. In patients with unplanned ICU admission, NFR orders were present in approximately 3% of cases. An NFR order was issued at the time of an “event” in 3.85% of cases in MET hospitals compared with 1.72% in control hospitals (OR=2.29; 95% CI: 1.31–4.01; p =0.005). This difference was mostly due to a greater proportion of patients being made NFR in MET hospitals at the time of a “adverse event-free” emergency team call (7.96% vs. 3.05%; OR=2.75; 95% CI: 0.97–7.80; p =0.048). The number of NFR orders issued at the time of a serious adverse event-free emergency team call was 10 times higher in MET hospitals (0.398 vs. 0.041 per 1000 admissions; weighted absolute risk difference: 0.49 (95% CI: 0.20–0.78; p =0.002). Multivariate models could only account for less than 50% of the variance in the issuing of NFR orders. Conclusions: In a cohort of Australian hospitals, most deaths occurred in patients with a previously documented NFR order but NFR orders were uncommon before cardiac arrest calls or unplanned ICU admissions. During the conduct of a cluster randomised controlled trial, more NFR orders were issued by emergency teams in those hospitals that implemented a MET system than in control hospitals. MET allocation, teaching hospital status, number of hospital beds and metropolitan location could only explain less than 50% of variance in NFR orders. [Copyright &y& Elsevier]

Objective: To document current management of blood glucose in Australian and New Zealand intensive care units (ICUs) and to investigate the association between insulin administration, blood glucose concentration and hospital outcome.Design and Setting: Practice survey and inception cohort study in closed multi-disciplinary ICUs in Australia and New Zealand.Patients: Twenty-nine ICU directors and 939 consecutive admissions to 29 ICUs during a 2-week period.Measurement and Results: Data collected included unit approaches to blood glucose management, patient characteristics, blood glucose concentrations, insulin administration and patient outcomes. Ten percent of the ICU directors reported using an intensive insulin regimen in all their patients. In 861 patients (91.7%) blood glucose concentration was greater than 6.1[Symbol: see text]mmol/l, 287 (31.1%) received insulin, and the median blood glucose concentration triggering insulin administration was 11.5 (IQR 9.4-14) mmol/l. Univariate analysis demonstrated that non-survivors had a higher maximum daily blood glucose concentration (12 mmol/l, 9.4-14.8, vs. 9.5, 7.6-12.2) and were more likely to receive insulin (47% vs. 28%). Multiple logistic regression analysis showed age (OR per 5-year decrease 0.93, 95% CI 0.87-1.00) and APACHE II (OR per point decrease 0.87, 95% CI 0.84-0.90) to be independently associated with hospital mortality. After controlling for age and APACHE II both daily highest blood glucose (OR 0.95, 95% CI 0.90-1.00) and administration of insulin (OR 0.62, 95% CI 0.39-1.00) were independently associated when added to the model alone; neither was independently associated when they were simultaneously included in the model.Conclusion: Few Australian and New Zealand ICUs have adopted intensive insulin therapy. In this study, insulin administration and highest daily blood glucose concentration could not be separated in their association with hospital mortality. [ABSTRACT FROM AUTHOR]

Objectives: The optimal time to initiate renal replacement therapy in critically ill patients with acute kidney injury is controversial. We investigated the effect of such earlier versus later initiation of renal replacement therapy on the primary outcome of 28-day mortality and other patient-centered secondary outcomes.Design: We searched MEDLINE (via PubMed), EMBASE, and Cochrane databases to July 17, 2020, and included randomized controlled trials comparing earlier versus later renal replacement therapy.Setting: Multiple centers involved in eight trials.Patients: Total of 4,588 trial participants.Intervention: Two independents investigators screened and extracted data using a predefined form. We selected randomized controlled trials in critically ill adult patients with acute kidney injury and compared of earlier versus later initiation of renal replacement therapy regardless of modality.Measurements and Main Results: Overall, 28-day mortality was similar between earlier and later renal replacement therapy initiation (38.43% vs 38.06%, respectively; risk ratio, 1.01; [95% CI, 0.94-1.09]; I2 = 0%). Earlier renal replacement therapy, however, shortened hospital length of stay (mean difference, -2.14 d; [95% CI, -4.13 to -0.14]) and ICU length of stay (mean difference, -1.18 d; [95% CI, -1.95 to -0.42]). In contrast, later renal replacement therapy decreased the use of renal replacement therapy (relative risk, 0.69; [95% CI, 0.58-0.82]) and lowered the risk of catheter-related blood stream infection (risk ratio, 0.50, [95% CI, 0.29-0.86). Among survivors, renal replacement therapy dependence at day 28 was similar between earlier and later renal replacement therapy initiation (risk ratio, 0.98; [95% CI, 0.66-1.40]).Conclusions: Earlier or later initiation of renal replacement therapy did not affect mortality. However, earlier renal replacement therapy was associated with significantly shorter ICU and hospital length of stay, whereas later renal replacement therapy was associated with decreased use of renal replacement therapy and decreased risk of catheter-related blood stream infection. These findings can be used to guide the management of critically ill patients with acute kidney injury. [ABSTRACT FROM AUTHOR]

Background: General medical wards admit a varied cohort of patients from the emergency department, some of whom deteriorate during their hospital stay. Currently, we use vital signs based warning scores to predict patients at risk of imminent deterioration, but there is now a growing body of literature that commonly available laboratory results may also help to identify those at risk. Aim: To assess whether a laboratory‐based admission score can predict in hospital mortality, intensive care unit (ICU) admission, medical emergency team (MET) activation or cardiac arrest in a cohort of Australian general medical patients admitted through the emergency department (ED). Methods: We performed a retrospective observational study of all general medical admissions to hospital through the ED in 2015. Admission pathology was used to calculate a risk score. In‐patient outcomes of death, ICU transfer, MET call activation or cardiac arrest were collected from hospital records. Results: We studied 2942 admissions derived from 2521 patients, with a median age of 81 years. There were 143 in‐patient deaths, 82 ICU admissions, 277 MET calls and 14 cardiac arrest calls. The laboratory‐based admission score had an area under the receiver operating characteristic curve (AUC‐ROC) of 0.76 (95% confidence interval (CI): 0.72–0.80) for inpatient death, an AUC‐ROC of 0.79 (95% CI: 0.66–0.93) for inpatient cardiac arrest, an AUC‐ROC of 0.64 (95% CI: 0.58–0.70) for ICU transfer and an AUC‐ROC of 0.59 (95% CI: 0.55–0.62) for MET call activation. When patients aged over 75 were analysed separately, the AUC‐ROC for prediction of in‐patient death was 0.74 (95% CI: 0.70–0.78) and increased to 0.86 (95% CI: 0.73–0.98) for the prediction of in‐patient cardiac arrest. Conclusion: A simple laboratory‐derived score obtained at patient admission is a fair to good predictor of subsequent in‐patient death or cardiac arrest in general medical patients and in the older patient cohort. Prospective interventional studies are required to ascertain the clinical utility of this admission score. [ABSTRACT FROM AUTHOR]

Background The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets. Methods We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations. Results We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4–8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35–65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P <.05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9–18.8), piperacillin was 78.6 mg/L (49.5–127.3), tazobactam was 9.5 mg/L (6.3–14.2), and vancomycin was 14.3 mg/L (11.6–21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively. Conclusions In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients. [ABSTRACT FROM AUTHOR]

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]

Objectives: To evaluate what proportion of unplanned ICU admissions from hospital wards occurred after rapid response team review and compare baseline characteristics and outcomes of patients admitted after rapid response team review with non-rapid response team-related admissions.Design: Multicenter binational retrospective cohort study.Setting: One-hundred seventy-eight ICUs across Australia and New Zealand.Patients: All adults (≥ 17 yr) in the Australian and New Zealand Intensive Care Society Adult Patient Database between 2012 and 2017.Interventions: None.Measurements and Main Results: Among 97,181 unplanned ICU admissions from the ward, prior rapid response team review occurred in 55,084 cases (56.7%). Rapid response team patients were slightly older (65.4 [16.9] vs 63.3 [18]), had a higher Acute Physiology and Chronic Health Evaluation III score (64.6 [27.1] vs 54.7 [25.3]) and more frequently had limitations of medical treatment (13.1% vs 8.5%) compared with patients with no rapid response team review. The strongest independent associations with ICU admission following rapid response team review included age, ICU admission diagnosis (especially sepsis-, neurologic-, respiratory-, and cardiovascular-related), tertiary ICU status, and presence of limitations of medical treatment (p < 0.0001 all comparisons). Rapid response team-related ICU admissions had a longer median ICU (2.4 d [1.2-4.6 d] vs 2.1 d [1.0-4.2 d]) and hospital (12.8 d [7.0-23.6 d] vs 10.8 d [5.9-20.3 d]) length of stay, and were more likely to die in the ICU (12.3% vs 7.5%) and in-hospital (20.8% vs 13.5%) (p < 0.0001). After adjusting for illness severity and institution, patients admitted following rapid response team review stayed longer in hospital but were not at increased risk of dying in-hospital (adjusted odds ratio, 1.03; 0.98-1.07).Conclusions: In Australia and New Zealand, hospital ward patients admitted to ICU following rapid response team review represent the majority of ward-based ICU admissions, are more chronically and acutely ill, and more frequently have sepsis than those admitted from the ward without rapid response team review. Their unadjusted outcomes are worse, but after adjustment their mortality is similar. [ABSTRACT FROM AUTHOR]

Objectives: To compare the characteristics of adults admitted to the ICU in Australia and New Zealand after trauma with nonelective, nontrauma admissions. To describe trends in hospital mortality and rates of discharge home among these two groups.Design: Retrospective review (2005-2017) of the Australia and New Zealand Intensive Care Society's Center for Outcome and Resource Evaluation Adult Patient Database.Setting: Adult ICUs in Australia and New Zealand.Patients: Adult (≥17 yr), nonelective, ICU admissions.Intervention: Observational study.Measurements and Main Results: We compared 77,002 trauma with 741,829 nonelective, nontrauma patients. Trauma patients were younger (49.0 ± 21.6 vs 60.6 ± 18.7 yr; p < 0.0001), predominantly male (73.1% vs 53.9%; p < 0.0001), and more frequently treated in tertiary hospitals (74.7% vs 45.8%; p < 0.0001). The mean age of trauma patients increased over time but was virtually static for nonelective, nontrauma patients (0.72 ± 0.02 yr/yr vs 0.03 ± 0.01 yr/yr; p < 0.0001). Illness severity increased for trauma but fell for nonelective, nontrauma patients (mean Australia and New Zealand risk of death: 0.10% ± 0.02%/yr vs -0.21% ± 0.01%/yr; p < 0.0001). Trauma patients had a lower hospital mortality than nonelective, nontrauma patients (10.0% vs 15.8%; p < 0.0001). Both groups showed an annual decline in the illness severity adjusted odds ratio (odds ratio) of hospital mortality, but this was slower among trauma patients (trauma: odds ratio 0.976/yr [0.968-0.984/yr; p < 0.0001]; nonelective, nontrauma: odds ratio 0.957/yr [0.955-0.959/yr; p < 0.0001]; interaction p < 0.0001). Trauma patients had lower rates of discharge home than nonelective, nontrauma patients (56.7% vs 64.6%; p < 0.0001). There was an annual decline in illness severity adjusted odds ratio of discharge home among trauma patients, whereas nonelective, nontrauma patients displayed an annual increase (trauma: odds ratio 0.986/yr [0.981-0.990/yr; p < 0.0001]; nonelective, nontrauma: odds ratio 1.014/yr [1.012-1.016/yr; p < 0.0001]; interaction: p < 0.0001).Conclusions: The age and illness severity of adult ICU trauma patients in Australia and New Zealand has increased over time. Hospital mortality is lower for trauma than other nonelective ICU patients but has fallen more slowly. Trauma patients have become less likely to be discharged home than other nonelective ICU patients. [ABSTRACT FROM AUTHOR]

Introduction: Little is known about early (first 48 h) hourly and cumulative fluid balance (FB) during continuous renal replacement therapy (CRRT). Objectives: To study the characteristics and outcome associations of early hourly and cumulative FB. Methods: We studied FB in CRRT patients (2016–2018). Results: Among 350 patients, mean hourly FB became negative after 20 CRRT hours, but within 6 CRRT hours in patients with baseline fluid overload. A negative early FB was never achieved in patients receiving vasopressor therapy (p < 0.001). Mortality was 31%. The percentage of hourly negative FB was independently associated with decreased ICU mortality. A time-weighted hourly FB between 18.5 and –33 mL/h was also significantly and independently associated with decreased mortality. Conclusions: In CRRT patients, an early FB conservative approach is possible, modulated by patient characteristics, and associated with a low mortality. Moreover, avoidance of an early positive FB is associated with decreased mortality. [ABSTRACT FROM AUTHOR]

Background: Hypotension following orthopaedic surgery has been associated with increased morbidity and mortality. Rapid response teams (RRT) review patients on hospital wards with hypotension. Aim: To evaluate the epidemiology of hypotensive RRT activations in adult orthopaedic patients to identify contributing factors and areas for future quality improvement. Methods: Timing of RRT activations, presumed causes of hypotension and associated treatments were assessed. Results: Among 963 RRT activations in 605 patients over 3 years, the first calls of 226 of 605 patients were due to hypotension, and 213 (94.2%) of 226 had sufficient data for analysis. The median age was 79 (interquartile range 66–87) years; 58 (27.2%) were male, and comorbidities were common. Most (68%) surgery was emergent, and 75.1% received intraoperative vasopressors for hypotension. Most activations occurred within 24 h of surgery, and hypovolaemia, infection and arrhythmias were common presumed causes. Fluid boluses occurred in 173 (81.2%), and the time between surgery and RRT activation was 10 (4.0–26.5) h. in cases where fluid boluses were given, compared with 33 (15.5–61.5) h. where they were not (P < 0.001). Blood transfusion (30, 14.1%) and withholding of medications were also common. Hospital mortality was 8.5% (18), and 13.6% (29) were admitted to critical care at some stage. In‐hospital death was associated with older age, functional dependence, arrhythmia and presumed infection. Conclusions: Hypotension‐related RRT calls in orthopaedic patients are common. Future interventional studies might focus on perioperative fluid therapy and vaso‐active medications, as well as withholding of anti‐hypertensive medications preoperatively. [ABSTRACT FROM AUTHOR]

Background: Delirium is common in hospitalised patients but its epidemiology remains poorly characterised. Aims: To test the hypothesis that patient demographics, clinical phenotype, management and outcomes of patient with delirium in hospital ward patients differ from intensive care unit (ICU) patients. Methods: Retrospective cohort of patients admitted to an Australian university‐affiliated hospital between March 2013 and April 2017 and coded for delirium at discharge using the International Classification of Diseases System, 10th revision, criteria. Results: Among 61 032 hospitalised patients, 2864 (4.7%) were coded for delirium. From these, we studied a random sample of 100 ward patients and 100 ICU patients. Ward patients were older (median age: 84 vs 65 years; P < 0.0001), more likely to have dementia (38% vs 2% for ICU patients; P < 0.0001) and less likely to have had surgery (24% vs 62%; P < 0.0001). Of ward patients, 74% had hypoactive delirium, while 64% of ICU patients had agitated delirium (P < 0.0001). Persistent delirium at hospital discharge was more common among ward patients (66% vs 17%, P < 0.0001). On multivariable analysis, age and dementia predicted persistent delirium, while surgery predicted recovery. Conclusions: Delirium in ward patients is profoundly different from delirium in ICU patients. It has a dominant hypoactive clinical phenotype, is preceded by dementia and is less likely to recover at hospital discharge. Therefore, delirium prevention, detection and goals of care should be adapted to the environment in which it occurs. [ABSTRACT FROM AUTHOR]

Background: Knowledge about patients with acute liver failure (ALF) in Australia and New Zealand (ANZ) is lacking. Aims: To evaluate whether the pattern of ALF would be similar to previous studies and whether, despite potentially low transplantation rates, mortality would be comparable. Methods: We obtained data from the ANZ Intensive Care Society Adult Patient Database and the ANZ Liver Transplant Registry for 10 years commencing 2005 and analysed for patient outcomes. Results: During the study period, 1 022 698 adults were admitted to intensive care units across ANZ, of which 723 had ALF. The estimated annual incidence of ALF over this period was 3.4/million people and increased over time (P = 0.001). ALF patients had high illness severity (Acute Physiology And Chronic Health Evaluation III 79.8 vs 50.1 in non‐ALF patients; P < 0.0001) and were more likely to be younger, female, pregnant and immunosuppressed. ALF was an independent predictor of mortality (odds ratio 1.5 (1.26–1.79); P < 0.0001). At less than 23%, the use of liver transplantation was low, but the mortality of 39% was similar to previous studies. Conclusions: ALF is a rare but increasing diagnosis in ANZ intensive care units. Low transplantation rates in ANZ for ALF do not appear to be associated with higher mortality rates than reported in the literature. [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]

Objective: Catecholamines have been the mainstay of pharmacological treatment of cardiogenic shock (CS). Recently, use of epinephrine has been associated with detrimental outcomes. In the present study we aimed to evaluate the association between epinephrine use and short-term mortality in all-cause CS patients.Design: We performed a meta-analysis of individual data with prespecified inclusion criteria: (1) patients in non-surgical CS treated with inotropes and/or vasopressors and (2) at least 15% of patients treated with epinephrine administrated alone or in association with other inotropes/vasopressors. The primary outcome was short-term mortality.Measurements and Results: Fourteen published cohorts and two unpublished data sets were included. We studied 2583 patients. Across all cohorts of patients, the incidence of epinephrine use was 37% (17-76%) and short-term mortality rate was 49% (21-69%). A positive correlation was found between percentages of epinephrine use and short-term mortality in the CS cohort. The risk of death was higher in epinephrine-treated CS patients (OR [CI] = 3.3 [2.8-3.9]) compared to patients treated with other drug regimens. Adjusted mortality risk remained striking in epinephrine-treated patients (n = 1227) (adjusted OR = 4.7 [3.4-6.4]). After propensity score matching, two sets of 338 matched patients were identified and epinephrine use remained associated with a strong detrimental impact on short-term mortality (OR = 4.2 [3.0-6.0]).Conclusions: In this very large cohort, epinephrine use for hemodynamic management of CS patients is associated with a threefold increase of risk of death. [ABSTRACT FROM AUTHOR]

Introduction: There is concern about excessive bleeding when low-molecular-weight heparins (LMWHs) are used for venous thromboembolism (VTE) prophylaxis in renal dysfunction. Our objective was to evaluate whether LMWH VTE prophylaxis was safe and effective in critically ill patients with renal dysfunction by conducting a subgroup analysis of PROTECT, a randomized blinded trial. Methods: We studied intensive care unit (ICU) patients with pre-ICU dialysis-dependent end-stage renal disease (ESRD; pre-specified subgroup; n = 118), or severe renal dysfunction at ICU admission (defined as ESRD or non-dialysis dependent with creatinine clearance [CrCl] <30 ml/min; post hoc subgroup; n = 590). We compared dalteparin, 5000 IU daily, with unfractionated heparin (UFH), 5000 IU twice daily, and considered outcomes of proximal leg deep vein thrombosis (DVT); pulmonary embolism (PE); any VTE; and major bleeding. Adjusted hazard ratios [HR] were calculated using Cox regression. Results: In patients with ESRD, there was no significant difference in DVT (8.3% vs. 5.2%, p = 0.76), any VTE (10.0% vs. 6.9%; p = 0.39) or major bleeding (5.0% vs. 8.6%; p = 0.32) between UFH and dalteparin. In patients with severe renal dysfunction, there was no significant difference in any VTE (10.0% vs. 6.4%; p = 0.07) or major bleeding (8.9% vs. 11.0%; p = 0.66) but an increase in DVT with dalteparin (7.6% vs. 3.7%; p = 0.04). Interaction p-values for comparisons of HRs (ESRD versus not) were non-significant. Conclusions: In critically ill patients with ESRD, or severe renal dysfunction, there was no significant difference in any VTE or major bleeding between UFH and dalteparin. Patients with severe renal dysfunction who received dalteparin had more proximal DVTs than those on UFH; this finding did not hold in patients with ESRD alone. [ABSTRACT FROM AUTHOR]

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]

Purpose: To use the World Health Organisation's International Classification of Functioning to measure disability following critical illness using patient-reported outcomes.Methods: A prospective, multicentre cohort study conducted in five metropolitan intensive care units (ICU). Participants were adults who had been admitted to the ICU, received more than 24 h of mechanical ventilation and survived to hospital discharge. The primary outcome was measurement of disability using the World Health Organisation's Disability Assessment Schedule 2.0. The secondary outcomes included the limitation of activities and changes to health-related quality of life comparing survivors with and without disability at 6 months after ICU.Results: We followed 262 patients to 6 months, with a mean age of 59 ± 16 years, and of whom 175 (67%) were men. Moderate or severe disability was reported in 65 of 262 (25%). Predictors of disability included a history of anxiety/depression [odds ratio (OR) 1.65 (95% confidence interval (CI) 1.22, 2.23), P = 0.001]; being separated or divorced [OR 2.87 (CI 1.35, 6.08), P = 0.006]; increased duration of mechanical ventilation [OR 1.04 (CI 1.01, 1.08), P = 0.03 per day]; and not being discharged to home from the acute hospital [OR 1.96 (CI 1.01, 3.70) P = 0.04]. Moderate or severe disability at 6 months was associated with limitation in activities, e.g. not returning to work or studies due to health (P < 0.002), and reduced health-related quality of life (P < 0.001).Conclusion: Disability measured using patient-reported outcomes was prevalent at 6 months after critical illness in survivors and was associated with reduced health-related quality of life. Predictors of moderate or severe disability included a prior history of anxiety or depression, separation or divorce and a longer duration of mechanical ventilation.Trial Registration: NCT02225938. [ABSTRACT FROM AUTHOR]

Background: In critically ill patients with permissive hyperglycemia, it is uncertain whether exogenous insulin administration suppresses or enhances c-peptide secretion (a marker of pancreatic beta-cell response). We aimed to explore this effect in patients with type 2 diabetes. Methods: We prospectively enrolled a cohort of 45 critically ill patients with type 2 diabetes managed according to a liberal glucose protocol (target blood glucose 10-14 mmol/l). We recorded the administration of insulin and oral hypoglycemic agents and measured plasma c-peptide as surrogate marker of endogenous insulin secretion on the first two consecutive days in ICU. Results: Overall, 20 (44.4%) patients required insulin to achieve target blood glucose. Insulin-treated patients had higher glycated hemoglobin A1c, more premorbid insulin-requiring type 2 diabetes, and greater blood glucose levels but lower c-peptide levels on admission. Premorbid insulin-requiring diabetes was independently associated with lower admission c-peptide, whereas greater plasma creatinine was independently associated with higher levels. Increases in c-peptide were positively correlated with an increase in blood glucose both in patients who did ( r = 0.54, P = 0.01) and did not ( r = 0.56, P = 0.004) receive insulin. However, insulin administration was independently associated with a greater increase in c-peptide ( P = 0.04). This association was not modified by the use of oral insulin secretagogues. Conclusions: C-peptide, a marker of beta-cell response, responds to and is influenced by glycemia and renal function in critically ill patients with type 2 diabetes. In addition, in our cohort, exogenous insulin administration was associated with a greater increase in c-peptide in response to hyperglycemia. Trial Registration Australian New Zealand Clinical Trials Registry (ACTRN12615000216516). [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]

Purpose: To estimate the prevalence, risk factors, prophylactic treatment and impact on mortality for venous thromboembolism (VTE) in patients with moderate to severe traumatic brain injury (TBI) treated in the intensive care unit.Methods: A post hoc analysis of the erythropoietin in traumatic brain injury (EPO-TBI) trial that included twice-weekly lower limb ultrasound screening. Venous thrombotic events were defined as ultrasound-proven proximal deep venous thrombosis (DVT) or clinically detected pulmonary embolism (PE). Results are reported as events, percentages or medians and interquartile range (IQR). Cox regression analysis was used to calculate adjusted hazard ratios (HR) with 95% confidence intervals (CI) for time to VTE and death.Results: Of 603 patients, 119 (19.7%) developed VTE, mostly comprising DVT (102 patients, 16.9%) with a smaller number of PE events (24 patients, 4.0%). Median time to DVT diagnosis was 6 days (IQR 2-11) and to PE diagnosis 6.5 days (IQR 2-16.5). Mechanical prophylaxis (MP) was used in 91% of patients on day 1, 97% of patients on day 3 and 98% of patients on day 7. Pharmacological prophylaxis was given in 5% of patients on day 1, 30% of patients on day 3 and 57% of patients on day 7. Factors associated with time to VTE were age (HR per year 1.02, 95% CI 1.01-1.03), patient weight (HR per kg 1.01, 95% CI 1-1.02) and TBI severity according to the International Mission for Prognosis and Analysis of Clinical Trials risk of poor outcome (HR per 10% increase 1.12, 95% CI 1.01-1.25). The development of VTE was not associated with mortality (HR 0.92, 95% CI 0.51-1.65).Conclusions: Despite mechanical and pharmacological prophylaxis, VTE occurs in one out of every five patients with TBI treated in the ICU. Higher age, greater weight and greater severity of TBI increase the risk. The development of VTE was not associated with excess mortality. [ABSTRACT FROM AUTHOR]

Objective The aim of the present paper is to study the indications for fluid bolus therapy (FBT) and its associated physiological changes in ED patients. Methods Prospective observational study of FBT in a tertiary ED, we recorded indications, number, types and volumes, resuscitation goals and perceived success rates of FBT. Moreover, we studied key physiological variables before, 10 min, 1 h and 2 h after FBT. Results We studied 500 FBT episodes (750 [500-1250] mL). Median age was 59 (36-76) years and 57% were male. Shock was deemed present in 135 (27%) patients, septic shock in 80 (16%), and cardiogenic shock in 30 (6%). Overall, 0.9% saline (84%) was the most common fluid and hypotension the most common indication (70%). 'Avoidance of hospital/ICU admission' was the goal perceived to have the greatest success rate (85%). However, although mean arterial pressure (MAP) increased ( P < 0.01) and heart rate (HR) decreased ( P = 0.04) at 10 min ( P = 0.01), both returned to baseline at 1 and 2 h. In contrast, respiratory rate (RR) increased at 1 ( P < 0.01) and 2 h ( P = 0.03) and temperature decreased at 1 and 2 h (both P < 0.001). In patients with shock, 1 h after FBT, there was a median 3 mmHg increase in MAP ( P = 0.01) but no change in HR ( P = 0.44), while RR increased ( P < 0.01) and temperature decreased ( P = 0.01). Conclusions In ED, FBT is used mostly in patients without shock. However, after an immediate haemodynamic effect, FBT is associated with absent or limited physiological changes at 1 or 2 h. Even in shocked patients, the changes in MAP at 1 or 2 h after FBT are small. [ABSTRACT FROM AUTHOR]

Background: In mechanically ventilated (MV) cardiac arrest (CA) survivors admitted to the intensive care unit (ICU) avoidance of hypoxia is considered crucial. However, avoidance of hyperoxia may also be important. A conservative approach to oxygen therapy may reduce exposure to both.Methods: We evaluated the introduction of conservative oxygen therapy (target SpO2 88-92% using the lowest FiO2) during MV for resuscitated CA patients admitted to the ICU.Results: We studied 912 arterial blood gas (ABG) datasets: 448 ABGs from 50 'conventional' and 464 ABGs from 50 'conservative' oxygen therapy patients. Compared to the conventional group, conservative group patients had significantly lower PaO2 values and FiO2 exposure (p<0.001, respectively); more received MV in a spontaneous ventilation mode (18% vs 2%; p=0.001) and more were exposed to a FiO2 of 0.21 (19 vs 0 patients, p=0.001). Additionally, according to mean PaO2, more conservative group patients were classified as normoxaemic (36 vs 16 patients, p<0.01) and fewer as hyperoxaemic (14 vs 33 patients, p<0.01). Finally, ICU length of stay was significantly shorter for conservative group patients (p=0.04). There was no difference in the proportion of survivors discharged from hospital with good neurological outcome (14/23 vs 12/22 patients, p=0.67).Conclusions: Our findings provide preliminary support for the feasibility and physiological safety of conservative oxygen therapy in patients admitted to ICU for MV support after cardiac arrest (Trial registration, NCT01684124). [ABSTRACT FROM AUTHOR]

Background: Terlipressin improves renal function in some patients with type-1 hepato-renal syndrome (HRS). Renal contrast-enhanced ultrasound (CEUS), a novel imaging modality, may help to predict terlipressin responsiveness. Objectives: We used CEUS to estimate the effect of terlipressin on the renal cortical microcirculation in type-1 HRS. Methods: We performed renal CEUS scans with destruction-replenishment sequences using Sonovue® (Bracco, Milano Italy) as a contrast agent at baseline and after the intravenous administration of 1 mg of terlipressin, in four patients with type-1 HRS. We analyzed video sequences offline using dedicated software. We derived a perfusion index (PI) at each time point for each patient. Results: Patients 1 and 2 had severe presentation and were admitted to the intensive care unit. Both showed a marked increase in PI (+216% and + 567% of baseline) in response to terlipressin. Patients 3 and 4 had less severe presentations and had a decrease in PI (−53% and −20% of baseline) in response to terlipressin. Patients 1, 2, and 4, but not patient 3, responded to terlipressin therapy with a decrease in serum creatinine to <150 µmol/L. Conclusions: CEUS detected changes in renal cortical microcirculation in response to terlipressin and demonstrated heterogeneous microvascular responses to terlipressin. These initial proof-of-concept findings justify future investigations. [ABSTRACT FROM AUTHOR]

Managing post-operative surgical patients can be complex, with many patients at risk of complications and mortality. We piloted a model for co-management of high risk surgical patients: the post-operative surveillance team (POST). We conducted a survey to test the proposition that POST would be popular with nurses and junior doctors. We conducted a questionnaire survey of nurses and doctors involved with the POST programme. Fifty-three nurses and 10 doctors responded to the survey: 60% response rate. Of 63 respondents: 62 (98%; 95% CI: 92-100%) agreed that POST was valuable, 61 (97%; 95% CI: 89-99%) agreed that POST should continue, and 61 (97%; 95% CI: 89-99%) agreed that they enjoyed working with POST. In open ended responses 39% commented that POST provided supervision, mentoring, education, or collaboration. We conclude that POST was popular with surgical ward nurses and doctors. This popularity is one factor supporting a permanent service. [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.

Purpose: To determine whether fever is associated with an increased or decreased risk of death in patients admitted to an intensive care unit (ICU) with infection. Methods: We evaluated the independent association between peak temperature in the first 24 h after ICU admission and in-hospital mortality according to whether there was an admission diagnosis of infection using a database of admissions to 129 ICUs in Australia and New Zealand (ANZ) ( n = 269,078). Subsequently, we sought to confirm or refute the ANZ database findings using a validation cohort of admissions to 201 ICUs in the UK ( n = 366,973). Results: A total of 29,083/269,078 (10.8%) ANZ patients and 103,191/366,973 (28.1%) of UK patients were categorised as having an infection. In the ANZ cohort, adjusted in-hospital mortality risk progressively decreased with increasing peak temperature in patients with infection. Relative to the risk at 36.5-36.9°C, the lowest risk was at 39-39.4°C (adjusted OR 0.56; 95% CI 0.48-0.66). In patients without infection, the adjusted mortality risk progressively increased above 39.0°C (adjusted OR 2.07 at 40.0°C or above; 95% CI 1.68-2.55). In the UK cohort, findings were similar with adjusted odds ratios at corresponding temperatures of 0.77 (95% CI 0.71-0.85) and 1.94 (95% CI 1.60-2.34) for infection and non-infection groups, respectively. Conclusions: Elevated peak temperature in the first 24 h in ICU is associated with decreased in-hospital mortality in critically ill patients with an infection; randomised trials are needed to determine whether controlling fever increases mortality in such patients. [ABSTRACT FROM AUTHOR]

Objective: We aim to evaluate the incidence and outcome of acute kidney injury (AKI) among critically ill adult patients with H1N1 2009 infection. Design and patients: From a prospectively collected influenza A (H1N1) 2009 bi-national, we identified 671 adult patients admitted to intensive care unit (ICU) from June 1 to August 31, 2009. Of these, 628 (93.6%) had admission and/or peak serum creatinine values during ICU stay. We defined AKI according to the creatinine criteria of the RIFLE classification. Results: Of 628 adult patients, 211 [33.6%, 95% confidence interval (CI) 29.8-37.4%] had AKI: 41 (6.5%) risk, 56 (8.9%) injury and 114 (18.2%) failure. Of all 211 AKI patients, 76 [36.0% (29.4-42.6%)] died in hospital (36.6% in risk, 25.0% in injury and 41.3% in failure group) compared with 33 of 408 (8.1%) patients without AKI. Among the 33 AKI patients treated with renal replacement therapy, 13 died (39.4%). Mechanical ventilation [odds ratio (OR) 3.62 (2.07-6.34)], any severe co-morbidity (OR 2.36, 95% CI 1.15-3.71), age (OR 1.02, 95% CI 1.01-1.03 per 1 year increase), and AKI (OR 6.69, 95% CI 4.25-10.55) were independently associated with hospital mortality. Conclusions: Acute kidney injury appears common in H1N1 2009 infected patients and is independently associated with an increased risk of hospital mortality. [ABSTRACT FROM AUTHOR]

The article reports the treatment of patients with severe H1N1 pneumonitis and immunoglobulin G2 subclass (IgG2) failing antiviral therapy with intravenous immunoglobulin (IVIG). It mentions the report to be the first of its kind in the treatment with IVIG. It informs about the unawareness of the therapeutic benefit of IVIG owing to the heterogeneity of illness duration and severity depending on a patient. It suggests IVIG therapy to be beneficial to patients and proposes further evaluation.