Dexmedetomidine and Propofol Sedation in Critically Ill Patients and Dose-associated 90-Day Mortality: A Secondary Cohort Analysis of a Randomized Controlled Trial (SPICE III).

The SPICE III (Sedation Practice in Intensive Care Evaluation) trial reported significant heterogeneity in mortality with dexmedetomidine treatment. Supplemental propofol was commonly used to achieve desirable sedation. To quantify the association of different infusion rates of dexmedetomidine and propofol, given in combination, with mortality and to determine if this is modified by age.

A pilot randomized clinical trial of cryopreserved versus liquid-stored platelet transfusion for bleeding in cardiac surgery: The cryopreserved versus liquid platelet-New Zealand pilot trial.

Background And Objectives: Platelets for transfusion have a shelf-life of 7 days, limiting availability and leading to wastage. Cryopreservation at -80°C extends shelf-life to at least 1 year, but safety and effectiveness are uncertain.

Materials And Methods: This single centre blinded pilot trial enrolled adult cardiac surgery patients who were at high risk of platelet transfusion.

: Efficacy of short-term cold storage prior to cryopreservation of spermatozoa in a threatened lizard.

Assisted reproductive technologies (ARTs) have a significant role to play in reptile conservation, yet are severely lacking. Previous attempts to cryopreserve spermatozoa in the threatened lizard Varanus panoptes achieved approximately 48% motile sperm post-thaw for samples frozen immediately after collection. However, the feasibility of extended cold storage before cryopreservation has not been tested.

Early sedation with dexmedetomidine in ventilated critically ill patients and heterogeneity of treatment effect in the SPICE III randomised controlled trial.

Purpose: To 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.

Methods: Bayesian 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.

Results: HTE was assessed according to age and clusters (based on 12 baseline characteristics) using a Bayesian hierarchical models.

Efficacy of short-term cold storage prior to cryopreservation of spermatozoa in a threatened lizard.

Assisted reproductive technologies (ARTs) have a significant role to play in reptile conservation, yet are severely lacking. Previous attempts to cryopreserve spermatozoa in the threatened lizard Varanus panoptes achieved approximately 48% motile sperm post-thaw for samples frozen immediately after collection. However, the feasibility of extended cold storage before cryopreservation has not been tested.

Optimal Sedation and Pain Management: A Patient- and Symptom-Oriented Paradigm.

In the critically ill patient, optimal pain and sedation management remains the cornerstone of achieving comfort, safety, and to facilitate complex life support interventions. Pain relief, using multimodal analgesia, is an integral component of any orchestrated approach to achieve clinically appropriate goals in critically ill patients. Sedative management, however, remains a significant challenge.

The effect of dexmedetomidine on vasopressor requirements in patients with septic shock: a subgroup analysis of the Sedation Practice in Intensive Care Evaluation [SPICE III] Trial.

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.

Gender differences in mortality and quality of life after septic shock: A post-hoc analysis of the ARISE study.

Purpose: To assess the impact of gender and pre-menopausal state on short- and long-term outcomes in patients with septic shock.

Material And Methods: Cohort study of the Australasian Resuscitation in Sepsis Evaluation (ARISE) trial, an international randomized controlled trial comparing early goal-directed therapy (EGDT) to usual care in patients with early septic shock, conducted between October 2008 and April 2014. The primary exposure in this analysis was legal gender and the secondary exposure was pre-menopausal state defined by chronological age (≤ 50 years).

Early Sedation with Dexmedetomidine in Critically Ill Patients.

Background: Dexmedetomidine produces sedation while maintaining a degree of arousability and may reduce the duration of mechanical ventilation and delirium among patients in the intensive care unit (ICU). The use of dexmedetomidine as the sole or primary sedative agent in patients undergoing mechanical ventilation has not been extensively studied.

Methods: In an open-label, randomized trial, we enrolled critically ill adults who had been undergoing ventilation for less than 12 hours in the ICU and were expected to continue to receive ventilatory support for longer than the next calendar day to receive dexmedetomidine as the sole or primary sedative or to receive usual care (propofol, midazolam, or other sedatives).

Quality of Life and 1-Year Survival in Patients With Early Septic Shock: Long-Term Follow-Up of the Australasian Resuscitation in Sepsis Evaluation Trial.

Objectives: To examine long-term survival and quality of life of patients with early septic shock.

Design: Prospective, randomized, parallel-group trial.

Setting: Fifty-one hospitals in Australia, New Zealand, Finland, Hong Kong, and the Republic of Ireland.

Sedation Intensity in the First 48 Hours of Mechanical Ventilation and 180-Day Mortality: A Multinational Prospective Longitudinal Cohort Study.

Objectives: In the absence of a universal definition of light or deep sedation, the level of sedation that conveys favorable outcomes is unknown. We quantified the relationship between escalating intensity of sedation in the first 48 hours of mechanical ventilation and 180-day survival, time to extubation, and delirium.

Design: Harmonized data from prospective multicenter international longitudinal cohort studies SETTING:: Diverse mix of ICUs.

The SPICE III study protocol and analysis plan: a randomised trial of early goaldirected sedation compared with standard care in mechanically ventilated patients.

Background: Sedation strategy in critically ill patients who are mechanically ventilated is influenced by patient-related factors, choice of sedative agent and the intensity or depth of sedation prescribed. The impact of sedation strategy on outcome, in particular when delivered early after initiation of mechanical ventilation, is uncertain.

Objectives: To present the protocol and analysis plan of a large randomised clinical trial investigating the effect of a sedation strategy, in critically ill patients who are mechanically ventilated, based on a protocol targeting light sedation using dexmedetomidine as the primary sedative, termed "early goal-directed sedation", compared with usual practice.

Considerations for co-enrolment in randomised controlled effectiveness trials in critical care: the SPICE-8 co-enrolment guidelines.

The Australian and New Zealand Intensive Care Society Clinical Trials Group and other investigator-led trials groups in critical care publish policies and guidelines outlining the rationale for considering co-enrolment in large, randomised controlled trials in intensive care medicine. However, none present a checklist of criteria by which a request for permission to co-enrol in an existing trial can be assessed. Consequently, such requests tend to be made and assessed on an ad hoc basis.

Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis.

Background: After a single-center trial and observational studies suggesting that early, goal-directed therapy (EGDT) reduced mortality from septic shock, three multicenter trials (ProCESS, ARISE, and ProMISe) showed no benefit. This meta-analysis of individual patient data from the three recent trials was designed prospectively to improve statistical power and explore heterogeneity of treatment effect of EGDT.

Methods: We harmonized entry criteria, intervention protocols, outcomes, resource-use measures, and data collection across the trials and specified all analyses before unblinding.

Health-Related Quality of Life in Australasian Survivors of H1N1 Influenza Undergoing Mechanical Ventilation. A Multicenter Cohort Study.

Rationale: Patients surviving acute respiratory distress syndrome suffer decrements in physical function and health-related quality of life (HR-QoL); however, it is unclear whether HR-QoL is disproportionately affected in those with H1N1 influenza.

Objectives: The objective was to compare the HR-QoL of patients with a diagnosis of H1N1 influenza who were mechanically ventilated, 12 months after intensive care unit (ICU) discharge with healthy population data and ICU survivor data.

Methods: A prospective, observational, binational, multicenter cohort study was conducted in 11 ICUs in Australia and New Zealand during June-September 2009.

Goal-directed resuscitation for patients with early septic shock.

Background: Early goal-directed therapy (EGDT) has been endorsed in the guidelines of the Surviving Sepsis Campaign as a key strategy to decrease mortality among patients presenting to the emergency department with septic shock. However, its effectiveness is uncertain.

Methods: In this trial conducted at 51 centers (mostly in Australia or New Zealand), we randomly assigned patients presenting to the emergency department with early septic shock to receive either EGDT or usual care.

Australasian Resuscitation In Sepsis Evaluation trial statistical analysis plan.

Background: The Australasian Resuscitation In Sepsis Evaluation (ARISE) study is an international, multicentre, randomised, controlled trial designed to evaluate the effectiveness of early goal-directed therapy compared with standard care for patients presenting to the ED with severe sepsis.

Objective: In keeping with current practice, and taking into considerations aspects of trial design and reporting specific to non-pharmacologic interventions, this document outlines the principles and methods for analysing and reporting the trial results. The document is prepared prior to completion of recruitment into the ARISE study, without knowledge of the results of the interim analysis conducted by the data safety and monitoring committee and prior to completion of the two related international studies.

The Australasian Resuscitation in Sepsis Evaluation (ARISE) trial statistical analysis plan.

Background: The Australasian Resuscitation in Sepsis Evaluation (ARISE) study is an international, multicentre, randomised, controlled trial designed to evaluate the effectiveness of early goal-directed therapy compared with standard care for patients presenting to the emergency department with severe sepsis.

Objective: In keeping with current practice, and considering aspects of trial design and reporting specific to non-pharmacological interventions, our plan outlines the principles and methods for analysing and reporting the trial results. The document is prepared before completion of recruitment into the ARISE study, without knowledge of the results of the interim analysis conducted by the data safety and monitoring committee and before completion of the two related international studies.

Early goal-directed sedation versus standard sedation in mechanically ventilated critically ill patients: a pilot study*.

Objective: To assess the feasibility and safety of delivering early goal-directed sedation compared with standard sedation.

Design: Pilot prospective, multicenter, randomized, controlled trial.

Setting: Six ICUs.

A multicenter randomized trial of atorvastatin therapy in intensive care patients with severe sepsis.

Rationale: Observational studies link statin therapy with improved outcomes in patients with severe sepsis.

Objectives: To test whether atorvastatin therapy affects biologic and clinical outcomes in critically ill patients with severe sepsis.

Methods: Phase II, multicenter, prospective, randomized, double-blind, placebo-controlled trial stratified by site and prior statin use.

Early intensive care sedation predicts long-term mortality in ventilated critically ill patients.

Rationale: Choice and intensity of early (first 48 h) sedation may affect short- and long-term outcome.

Objectives: 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).

Methods: 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.

Critical care services and the H1N1 (2009) influenza epidemic in Australia and New Zealand in 2010: the impact of the second winter epidemic.

Introduction: During the first winter of exposure, the H1N1 2009 influenza virus placed considerable strain on intensive care unit (ICU) services in Australia and New Zealand (ANZ). We assessed the impact of the H1N1 2009 influenza virus on ICU services during the second (2010) winter, following the implementation of vaccination.

Methods: A prospective, cohort study was conducted in all ANZ ICUs during the southern hemisphere winter of 2010.