Explore the vast range of titles available.

Background Septic shock is associated with decreased vasopressor responsiveness. Experimental data suggest that central alpha2-agonists like dexmedetomidine (DEX) increase vasopressor responsiveness and reduce catecholamine requirements in septic shock. However, DEX may also cause hypotension and bradycardia. Thus, it remains unclear whether DEX is hemodynamically safe or helpful in this setting. Methods In this post hoc subgroup analysis of the Sedation Practice in Intensive Care Evaluation (SPICE III) trial, an international randomized trial comparing early sedation with dexmedetomidine to usual care in critically patients receiving mechanical ventilation, we studied patients with septic shock admitted to two tertiary ICUs in Australia and Switzerland. The primary outcome was vasopressor requirements in the first 48 h after randomization, expressed as noradrenaline equivalent dose (NEq [μg/kg/min] = noradrenaline + adrenaline + vasopressin/0.4). Results Between November 2013 and February 2018, 417 patients were recruited into the SPICE III trial at both sites. Eighty-three patients with septic shock were included in this subgroup analysis. Of these, 44 (53%) received DEX and 39 (47%) usual care. Vasopressor requirements in the first 48 h were similar between the two groups. Median NEq dose was 0.03 [0.01, 0.07] μg/kg/min in the DEX group and 0.04 [0.01, 0.16] μg/kg/min in the usual care group ( p  = 0.17). However, patients in the DEX group had a lower NEq/MAP ratio, indicating lower vasopressor requirements to maintain the target MAP. Moreover, on adjusted multivariable analysis, higher dexmedetomidine dose was associated with a lower NEq/MAP ratio. Conclusions In critically ill patients with septic shock, patients in the DEX group received similar vasopressor doses in the first 48 h compared to the usual care group. On multivariable adjusted analysis, dexmedetomidine appeared to be associated with lower vasopressor requirements to maintain the target MAP. Trial registration The SPICE III trial was registered at ClinicalTrials.gov ( NCT01728558 ).

In a randomized trial involving 4000 patients in the ICU who required sedation for mechanical ventilation, dexmedetomidine had no benefit on 90-day mortality as compared with usual care and was associated with more adverse events. Additional drugs were required for prescribed sedation levels in the two groups.

For more than a decade, early treatment of sepsis has been driven by algorithms. In this study conducted predominantly in Australia and New Zealand, the use of algorithm-based treatment was not superior to usual care. Severe sepsis has a reported annual incidence in adults of up to 300 cases per 100,000 population. 1 – 3 Despite decreasing mortality from sepsis in recent years, 4 the risk of death remains high. 5 , 6 The fundamental principles for the management of sepsis include early recognition, control of the source of infection, appropriate and timely administration of antimicrobial drugs, and resuscitation with intravenous fluids and vasoactive drugs. Patients presenting to the emergency department account for a large proportion of patients with severe sepsis. 7 Reported in-hospital mortality ranges in this subgroup from 20 to 50%. 3 , 8 – 10 In 2001, a proof-of-concept, randomized trial . . .

Choice and intensity of early (first 48 h) sedation may affect short- and long-term outcome. To investigate the relationships between early sedation and time to extubation, delirium, and hospital and 180-day mortality among ventilated critically ill patients in the intensive care unit (ICU). Multicenter (25 Australia and New Zealand hospitals) prospective longitudinal (ICU admission to 28 d) cohort study of medical/surgical patients ventilated and sedated 24 hours or more. We assessed administration of sedative agents, ventilation time, sedation depth using Richmond Agitation Sedation Scale (RASS, four hourly), delirium (daily), and hospital and 180-day mortality. We used multivariable Cox regression to quantify relationships between early deep sedation (RASS, -3 to -5) and patients' outcomes. We studied 251 patients (mean age, 61.7 ± 15.9 yr; mean Acute Physiology and Chronic Health Evaluation [APACHE] II score, 20.8 ± 7.8), with 21.1% (53) hospital and 25.8% (64) 180-day mortality. Over 2,678 study days, we completed 14,736 RASS assessments. Deep sedation occurred in 191 (76.1%) patients within 4 hours of commencing ventilation and in 171 (68%) patients at 48 hours. Delirium occurred in 111 (50.7%) patients with median (interquartile range) duration of 2 (1-4) days. After adjusting for diagnosis, age, sex, APACHE II, operative, elective, hospital type, early use of vasopressors, and dialysis, early deep sedation was an independent predictor of time to extubation (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.87-0.94; P < 0.001), hospital death (HR, 1.11; 95% CI, 1.02-1.20; P = 0.01), and 180-day mortality (HR, 1.08; 95% CI, 1.01-1.16; P = 0.026) but not delirium occurring after 48 hours (P = 0.19). Early sedation depth independently predicts delayed extubation and increased mortality, making it a potential target for interventional studies.

PurposeTo quantify potential heterogeneity of treatment effect (HTE), of early sedation with dexmedetomidine (DEX) compared with usual care, and identify patients who have a high probability of lower or higher 90-day mortality according to age, and other identified clusters.MethodsBayesian analysis of 3904 critically ill adult patients expected to receive invasive ventilation > 24 h and enrolled in a multinational randomized controlled trial comparing early DEX with usual care sedation.ResultsHTE was assessed according to age and clusters (based on 12 baseline characteristics) using a Bayesian hierarchical models. DEX was associated with lower 90-day mortality compared to usual care in patients > 65 years (odds ratio [OR], 0.83 [95% credible interval [CrI] 0.68–1.00], with 97.7% probability of reduced mortality across broad categories of illness severity. Conversely, the probability of increased mortality in patients ≤ 65 years was 98.5% (OR 1.26 [95% CrI 1.02–1.56]. Two clusters were identified: cluster 1 (976 patients) mostly operative, and cluster 2 (2346 patients), predominantly non-operative. There was a greater probability of benefit with DEX in cluster 1 (OR 0.86 [95% CrI 0.65–1.14]) across broad categories of age, with 86.4% probability that DEX is more beneficial in cluster 1 than cluster 2.ConclusionIn critically ill mechanically ventilated patients, early sedation with dexmedetomidine exhibited a high probability of reduced 90-day mortality in older patients regardless of operative or non-operative cluster status. Conversely, a high probability of increased 90-day mortality was observed in younger patients of non-operative status. Further studies are needed to confirm these findings.

IntroductionInternational consensus guidelines support the initial administration of 30 mL/kg of intravenous fluids for haemodynamic resuscitation of newly diagnosed septic shock. Practice variation exists between the volume of fluids administered and timing of vasopressor commencement. The optimal approach in patients with septic shock is uncertain.Methods and analysisAustralasian Resuscitation In Sepsis Evaluation: FLUid or vasopressors In emergency Department Sepsis is a 1000-participant multicentre, randomised, open-label, parallel group clinical trial conducted in patients with septic shock presenting to the emergency department in participating sites in Australia, New Zealand and Ireland. Participants are randomised (1:1) to either restricted fluids and early vasopressors or a larger initial intravenous fluid volume and later vasopressors. The primary outcome is days alive and out of hospital at day 90 postrandomisation. Secondary outcomes are all-cause mortality at day 90, time from randomisation until death (to day 90), days alive and at home at day 90 and ventilator-free, vasopressor-free and renal replacement-free days to day 28 postrandomisation and death or disability at 6-month and 12-month postrandomisation. Health-related quality of life will be assessed at day 180 and 12 months following randomisation.Ethics and disseminationThe study was approved by Northern Sydney Local Health District Human Research Ethics Committee (HREC2020/ETH02874) on 21 January 2021. Patients will be enrolled under a waiver of prior consent. The patient or next-of-kin (or equivalent according to local jurisdiction) is approached at the first available opportunity and given a trial information sheet. According to local approvals, the patient or next-of-kin chooses to either continue in the trial or opt-out/decline continued participation. Results will be disseminated in peer-reviewed journals and presented at academic conferences.Trial registration numberNCT04569942

IntroductionCryopreservation at −80°C in dimethylsulphoxide extends platelet shelf-life from 7 days to 2 years. Only limited comparative trial data supports the safety and effectiveness of cryopreserved platelets as a treatment for surgical bleeding. Cryopreserved platelets are not currently registered for civilian use in most countries.Methods and analysisCLIP-II and CLIPNZ-II are harmonised, blinded, multicentre, randomised, controlled clinical non-inferiority trials comparing bleeding, transfusion, safety and cost outcomes associated with cryopreserved platelets versus conventional liquid platelets as treatment for bleeding in cardiac surgery. CLIP-II is planning to enrol patients in 12 tertiary hospitals in Australia; CLIPNZ-II will recruit in five tertiary hospitals in New Zealand. The trials use near-identical protocols aside from details of cryopreserved platelet preparation. Patients identified preoperatively as being at high risk of requiring a platelet transfusion receive up to three units of study platelets if their treating doctor considers platelet transfusion is indicated. The primary endpoint is blood loss through the surgical drains in the 24 hours following intensive care unit (ICU) admission after surgery. Other endpoints are blood loss at other time points, potential complications, adverse reactions, transfusion and fluid requirement, requirement for procoagulant treatments, time to commencement of postoperative anticoagulants, delay between platelet order and commencement of infusion, need for reoperation, laboratory and point-of-care clotting indices, cost, length of mechanical ventilation, ICU and hospital stay, and mortality. Transfusing 202 (CLIP-II) or 228 (CLIPNZ-II) patients with study platelets will provide 90% power to exclude the possibility of greater than 20% inferiority in the primary endpoint. If cryopreserved platelets are not inferior to liquid-stored platelets, the advantages of longer shelf-life would justify rapid change in clinical practice. Cost-effectiveness analyses will be incorporated into each study such that, should clinical non-inferiority compared with standard care be demonstrated, the hospitals in each country that would benefit most from changing to a cryopreserved platelet blood bank will be known.Ethics and disseminationCLIP-II was approved by the Austin Health Human Research Ethics Committee (HREC/54406/Austin-2019) and by the Australian Red Cross Lifeblood Ethics Committee (2019#23). CLIPNZ-II was approved by the New Zealand Southern Health and Disability Ethics Committee (21/STH/66). Eligible patients are approached for informed consent at least 1 day prior to surgery. There is no provision for consent provided by a substitute decision-maker. The results of the two trials will be submitted separately for publication in peer-reviewed journals.Trial registration numbersNCT03991481 and ACTRN12621000271808.

This study presents a patient-level meta-analysis of three recent trials of early, goal-directed therapy for septic shock. Results showed that EGDT did not improve outcomes and increased hospitalization costs across a broad range of patient and hospital characteristics. In 2001, Rivers and colleagues reported on a 263-patient, single-center, randomized, controlled trial of early, goal-directed therapy (EGDT) versus usual care in patients presenting with septic shock to an urban emergency department in the United States. 1 EGDT is a 6-hour resuscitation protocol for the administration of intravenous fluids, vasopressors, inotropes, and red-cell transfusion to achieve prespecified targets for arterial blood pressure, central venous pressure, central venous oxygen saturation, and hemoglobin level. EGDT reduced hospital mortality from 46.5% to 30.5%, 1 prompting many institutions worldwide to adopt EGDT. 2 Three subsequent, government-funded, multicenter, randomized, controlled trials from the United States (Protocolized Care for . . .

Observational studies link statin therapy with improved outcomes in patients with severe sepsis. To test whether atorvastatin therapy affects biologic and clinical outcomes in critically ill patients with severe sepsis. Phase II, multicenter, prospective, randomized, double-blind, placebo-controlled trial stratified by site and prior statin use. A cohort of 250 critically ill patients (123 statins, 127 placebo) with severe sepsis were administrated either atorvastatin (20 mg daily) or matched placebo. There was no difference in IL-6 concentrations (primary end point) between the atorvastatin and placebo groups (P = 0.76) and no interaction between treatment group and time to suggest that the groups behaved differently over time (P = 0.26). Baseline plasma IL-6 was lower among previous statin users (129 [87-191] vs. 244 [187-317] pg/ml; P = 0.01). There was no difference in length of stay, change in Sequential Organ Failure Assessment scores or mortality at intensive care unit discharge, hospital discharge, 28- or 90-day (15% vs. 19%), or adverse effects between the two groups. Cholesterol was lower in patients treated with atorvastatin (2.4 [0.07] vs. 2.6 [0.06] mmol/L; P = 0.006). In the predefined group of 77 prior statin users, those randomized to placebo had a greater 28-day mortality (28% vs. 5%; P = 0.01) compared with those who received atorvastatin. The difference was not statistically significant at 90 days (28% vs. 11%; P = 0.06). Atorvastatin therapy in severe sepsis did not affect IL-6 levels. Prior statin use was associated with a lower baseline IL-6 concentration and continuation of atorvastatin in this cohort was associated with improved survival. Clinical trial registered with the Australian New Zealand Clinical Trials Registry (ACTRN 12607000028404).

In this study, a consortium of intensive care units (ICUs) in Australia and New Zealand reported their experience with admissions associated with infection with the 2009 H1N1 virus. The overall rate of ICU admission was estimated to be 28.7 per million persons, approximately 15 times that in previous years. During the period of peak transmission in communities, the ICU bed-occupancy rate ranged from 8.9 to 19.0%. A consortium of ICUs in Australia and New Zealand report their experience with admissions associated with infection with the 2009 H1N1 virus. Infection with the 2009 pandemic influenza A (H1N1) virus emerged in Mexico toward the end of the 2008–2009 influenza season in the Northern Hemisphere. As of September 6, 2009, the World Health Organization had reported over 277,607 laboratory-confirmed cases of 2009 H1N1 influenza, with at least 3205 deaths. 1 From June through August 2009, Australia and New Zealand experienced the combined effect of the pandemic and winter in the Southern Hemisphere. The reported incidence of infection with the 2009 H1N1 virus during winter in Australia and New Zealand was 8 times that reported for the same period in the United States. . . .