Fever management

Paracetamol is one of the world’s most widely used medicines and is commonly given to Intensive Care Unit (ICU) patients with infections.  Despite prevailing practice, there is a sound rationale for the hypothesis that administration of paracetamol to patients with infection is harmful.  Investigators from MRINZ led a retrospective study which included 636,051 ICU patients from five countries.  This study showed that although the presence of fever in the first 24 hours after ICU admission was associated with an increased risk of mortality in patients without infection, it was associated with a decreased risk of mortality in those with an infection.  In response to these data we conducted a 700 patient clinical trial in 23 ICUs comparing paracetamol to placebo in ICU patients with fever and infection.  This study was endorsed by the Australian and New Zealand Intensive Care Society Clinical Trials Group, funded by the Health Research Council of New Zealand, and conducted in partnership with the George Institute for Global Health, Sydney, Australia.  We expect to publish the results of this trial in early 2015. 

Oxygen therapy

Oxygen is common treatment in patients who need care in an ICU.  In partnership with investigators in Australia and France we are undertaking a programme of research which we hope will lead to a definitive trial evaluating conservative vs. liberal oxygen therapy in ICU patients.  We have recently completed a feasibility study of titrated oxygen therapy vs. standard care in patients resuscitated from cardiac arrest in the community.  This study was funded by the Health Research Council of New Zealand and conducted in partnership with Wellington Free Ambulance, Hutt Valley DHB, and Capital and Coast DHB.  We demonstrated that it was feasible to randomise patients into a clinical trial in the community and to maintain a study intervention throughout the pre-hospital, emergency department, and ICU phases of care.  While titrating oxygen delivery in the pre-hospital setting proved to be impractical, this study demonstrated our capacity to conduct collaborative research involving the pre-hospital, emergency department, and ICU phases of care.

Read an interview with Project Manager, Diane Mackle.

Fluid management

Acutely ill patients are commonly treated with intravenous fluids. We are conducting a study (the SPLIT study) comparing the effectiveness of two commonly used intravenous fluids.  The study will enrol >2000 participants from four New Zealand hospitals and will compare the routine use of 0.9% saline for fluid therapy with Plasma Lyte® 148 in ICU patients.  The study hypothesis is that routinely using Plasma Lyte® 148 for fluid therapy instead of 0.9% saline will reduce the risk of developing acute kidney failure.  Kidney failure which occurs in the setting of acute illness is associated with a high risk of death and may require treatment with costly kidney dialysis treatments.  This study addresses an issue of major global public health significance because more than a million litres of 0.9% saline are currently administered to patients around the world daily.  The study is funded by the Health Research Council of New Zealand and Baxter Pty Ltd.

Dr Rachael Parke is leading a research programme evaluating approaches to fluid resuscitation after cardiac surgery.  We are currently seeking funding from the Health Research Council of New Zealand to conduct a phase II study comparing a fluid algorithm designed to reduce post-operative fluid use with standard care.  The study hypothesis is that ensuring that intravenous fluid boluses are only administered to patients who require them will reduce the amount of time which patients need to spend in the ICU after cardiac surgery.

The statistical analysis plan for the 0.9% Saline vs. Plasma-Lyte 148® for Intensive care fluid Therapy (SPLIT) study is available at: http://wellingtonicu.com/Data/Trials/SPLITSAP.pdf

Nutrition

Nutrition therapy is an essential standard of care for all ICU patients who are mechanically ventilated and remain in ICU for more than a few days. There is a substantial and well established dissociation between the recommended calorie requirement and calories actually delivered to ICU patients. Nevertheless, while it remains logical that energy delivery should match energy consumption, the benefits of such matching remain to be confirmed by a robust, high quality clinical trial.  We are working with Australian investigators who have recently completed a pilot study demonstrating that delivery of full-recommended calorie requirements to mechanically ventilated ICU patients may improve 90-day survival. We are currently seeking funding from the Health Research Council of New Zealand to determine if delivery of the full recommended calorie (energy) requirement to critically ill patients improves 90 day survival when compared to standard practice.

Selective decontamination of the digestive tract

Selective Digestive Decontamination (SDD) consists of a short course of antibiotic and antifungal treatment given to reduce the risk of developing hospital-acquired infection. We have recently received funding from the Health Research Council of New Zealand for the SuDDICU trial.  The SuDDICU trial is a ‘cluster randomised trial’ in which 100 ICUs in four countries, including three ICUs in NZ, will be assigned to use either SDD or standard therapy. As well as establishing whether SDD saves lives, this study will also establish whether SDD changes the numbers of antibiotic-resistant bacteria in the ICU. If the potential benefits of this treatment are realised, the results of this study will have global impact in terms of lives saved and infections prevented as well as potentially allowing large savings in health care spending.

Stress ulcer prophylaxis

The administration of stress ulcer prophylaxis (SUP), either with a Proton Pump Inhibitor (PPI) or a Histamine-2 Receptor Blocker (H₂RB) is recommended in international guidelines and incorporated into quality-oriented checklists for care of ICU patients. Our recent data show that PPIs and H₂RBs are routinely used for SUP in Australia and New Zealand with the choice of medication probably not based on patient factors, but instead dependent on clinician preference or unit policy. This practice variation reflects the lack of definitive evidence comparing PPIs to H₂RBs in the ICU setting. Although data suggest PPIs are more effective at reducing upper GI bleeding risk in ICU patients than H₂RBs, it also appears that using PPIs in ICU patients is associated with a 17-20% increase in pneumonia risk compared to H₂RBs, and that PPI use but not H₂RB use is associated with increased risk of Clostridium difficile infection. The overall influence of the opposing risks of upper GI bleeding and SUP-related infectious complications on in-hospital mortality is unknown.  We are currently seeking funding from the Health Research Council of New Zealand to lead a multicentre, multinational trial comparing the safety and efficacy of PPIs vs. H₂RBs in 40,000 mechanically ventilated ICU patients. 

Fever management

Paracetamol is one of the world’s most widely used medicines and is commonly given to Intensive Care Unit (ICU) patients with infections.  Despite prevailing practice, there is a sound rationale for the hypothesis that administration of paracetamol to patients with infection is harmful.  Investigators from MRINZ led a retrospective study which included 636,051 ICU patients from five countries.  This study showed that although the presence of fever in the first 24 hours after ICU admission was associated with an increased risk of mortality in patients without infection, it was associated with a decreased risk of mortality in those with an infection.  In response to these data we conducted a 700 patient clinical trial in 23 ICUs comparing paracetamol to placebo in ICU patients with fever and infection.  This study was endorsed by the Australian and New Zealand Intensive Care Society Clinical Trials Group, funded by the Health Research Council of New Zealand, and conducted in partnership with the George Institute for Global Health, Sydney, Australia.  We expect to publish the results of this trial in early 2015. 

Oxygen therapy

Oxygen is common treatment in patients who need care in an ICU.  In partnership with investigators in Australia and France we are undertaking a programme of research which we hope will lead to a definitive trial evaluating conservative vs. liberal oxygen therapy in ICU patients.  We have recently completed a feasibility study of titrated oxygen therapy vs. standard care in patients resuscitated from cardiac arrest in the community.  This study was funded by the Health Research Council of New Zealand and conducted in partnership with Wellington Free Ambulance, Hutt Valley DHB, and Capital and Coast DHB.  We demonstrated that it was feasible to randomise patients into a clinical trial in the community and to maintain a study intervention throughout the pre-hospital, emergency department, and ICU phases of care.  While titrating oxygen delivery in the pre-hospital setting proved to be impractical, this study demonstrated our capacity to conduct collaborative research involving the pre-hospital, emergency department, and ICU phases of care.

Read an interview with Project Manager, Diane Mackle.

Fluid management

Acutely ill patients are commonly treated with intravenous fluids. We are conducting a study (the SPLIT study) comparing the effectiveness of two commonly used intravenous fluids.  The study will enrol >2000 participants from four New Zealand hospitals and will compare the routine use of 0.9% saline for fluid therapy with Plasma Lyte® 148 in ICU patients.  The study hypothesis is that routinely using Plasma Lyte® 148 for fluid therapy instead of 0.9% saline will reduce the risk of developing acute kidney failure.  Kidney failure which occurs in the setting of acute illness is associated with a high risk of death and may require treatment with costly kidney dialysis treatments.  This study addresses an issue of major global public health significance because more than a million litres of 0.9% saline are currently administered to patients around the world daily.  The study is funded by the Health Research Council of New Zealand and Baxter Pty Ltd.

Dr Rachael Parke is leading a research programme evaluating approaches to fluid resuscitation after cardiac surgery.  We are currently seeking funding from the Health Research Council of New Zealand to conduct a phase II study comparing a fluid algorithm designed to reduce post-operative fluid use with standard care.  The study hypothesis is that ensuring that intravenous fluid boluses are only administered to patients who require them will reduce the amount of time which patients need to spend in the ICU after cardiac surgery.

The statistical analysis plan for the 0.9% Saline vs. Plasma-Lyte 148® for Intensive care fluid Therapy (SPLIT) study is available at: http://wellingtonicu.com/Data/Trials/SPLITSAP.pdf

Nutrition

Nutrition therapy is an essential standard of care for all ICU patients who are mechanically ventilated and remain in ICU for more than a few days. There is a substantial and well established dissociation between the recommended calorie requirement and calories actually delivered to ICU patients. Nevertheless, while it remains logical that energy delivery should match energy consumption, the benefits of such matching remain to be confirmed by a robust, high quality clinical trial.  We are working with Australian investigators who have recently completed a pilot study demonstrating that delivery of full-recommended calorie requirements to mechanically ventilated ICU patients may improve 90-day survival. We are currently seeking funding from the Health Research Council of New Zealand to determine if delivery of the full recommended calorie (energy) requirement to critically ill patients improves 90 day survival when compared to standard practice.

Selective decontamination of the digestive tract

Selective Digestive Decontamination (SDD) consists of a short course of antibiotic and antifungal treatment given to reduce the risk of developing hospital-acquired infection. We have recently received funding from the Health Research Council of New Zealand for the SuDDICU trial.  The SuDDICU trial is a ‘cluster randomised trial’ in which 100 ICUs in four countries, including three ICUs in NZ, will be assigned to use either SDD or standard therapy. As well as establishing whether SDD saves lives, this study will also establish whether SDD changes the numbers of antibiotic-resistant bacteria in the ICU. If the potential benefits of this treatment are realised, the results of this study will have global impact in terms of lives saved and infections prevented as well as potentially allowing large savings in health care spending.

Stress ulcer prophylaxis

The administration of stress ulcer prophylaxis (SUP), either with a Proton Pump Inhibitor (PPI) or a Histamine-2 Receptor Blocker (H₂RB) is recommended in international guidelines and incorporated into quality-oriented checklists for care of ICU patients. Our recent data show that PPIs and H₂RBs are routinely used for SUP in Australia and New Zealand with the choice of medication probably not based on patient factors, but instead dependent on clinician preference or unit policy. This practice variation reflects the lack of definitive evidence comparing PPIs to H₂RBs in the ICU setting. Although data suggest PPIs are more effective at reducing upper GI bleeding risk in ICU patients than H₂RBs, it also appears that using PPIs in ICU patients is associated with a 17-20% increase in pneumonia risk compared to H₂RBs, and that PPI use but not H₂RB use is associated with increased risk of Clostridium difficile infection. The overall influence of the opposing risks of upper GI bleeding and SUP-related infectious complications on in-hospital mortality is unknown.  We are currently seeking funding from the Health Research Council of New Zealand to lead a multicentre, multinational trial comparing the safety and efficacy of PPIs vs. H₂RBs in 40,000 mechanically ventilated ICU patients. 

Fever management

Paracetamol is one of the world’s most widely used medicines and is commonly given to Intensive Care Unit (ICU) patients with infections.  Despite prevailing practice, there is a sound rationale for the hypothesis that administration of paracetamol to patients with infection is harmful.  Investigators from MRINZ led a retrospective study which included 636,051 ICU patients from five countries.  This study showed that although the presence of fever in the first 24 hours after ICU admission was associated with an increased risk of mortality in patients without infection, it was associated with a decreased risk of mortality in those with an infection.  In response to these data we conducted a 700 patient clinical trial in 23 ICUs comparing paracetamol to placebo in ICU patients with fever and infection.  This study was endorsed by the Australian and New Zealand Intensive Care Society Clinical Trials Group, funded by the Health Research Council of New Zealand, and conducted in partnership with the George Institute for Global Health, Sydney, Australia.  We expect to publish the results of this trial in early 2015. 

Oxygen therapy

Oxygen is common treatment in patients who need care in an ICU.  In partnership with investigators in Australia and France we are undertaking a programme of research which we hope will lead to a definitive trial evaluating conservative vs. liberal oxygen therapy in ICU patients.  We have recently completed a feasibility study of titrated oxygen therapy vs. standard care in patients resuscitated from cardiac arrest in the community.  This study was funded by the Health Research Council of New Zealand and conducted in partnership with Wellington Free Ambulance, Hutt Valley DHB, and Capital and Coast DHB.  We demonstrated that it was feasible to randomise patients into a clinical trial in the community and to maintain a study intervention throughout the pre-hospital, emergency department, and ICU phases of care.  While titrating oxygen delivery in the pre-hospital setting proved to be impractical, this study demonstrated our capacity to conduct collaborative research involving the pre-hospital, emergency department, and ICU phases of care.

Read an interview with Project Manager, Diane Mackle.

Fluid management

Acutely ill patients are commonly treated with intravenous fluids. We are conducting a study (the SPLIT study) comparing the effectiveness of two commonly used intravenous fluids.  The study will enrol >2000 participants from four New Zealand hospitals and will compare the routine use of 0.9% saline for fluid therapy with Plasma Lyte® 148 in ICU patients.  The study hypothesis is that routinely using Plasma Lyte® 148 for fluid therapy instead of 0.9% saline will reduce the risk of developing acute kidney failure.  Kidney failure which occurs in the setting of acute illness is associated with a high risk of death and may require treatment with costly kidney dialysis treatments.  This study addresses an issue of major global public health significance because more than a million litres of 0.9% saline are currently administered to patients around the world daily.  The study is funded by the Health Research Council of New Zealand and Baxter Pty Ltd.

Dr Rachael Parke is leading a research programme evaluating approaches to fluid resuscitation after cardiac surgery.  We are currently seeking funding from the Health Research Council of New Zealand to conduct a phase II study comparing a fluid algorithm designed to reduce post-operative fluid use with standard care.  The study hypothesis is that ensuring that intravenous fluid boluses are only administered to patients who require them will reduce the amount of time which patients need to spend in the ICU after cardiac surgery.

The statistical analysis plan for the 0.9% Saline vs. Plasma-Lyte 148® for Intensive care fluid Therapy (SPLIT) study is available at: http://wellingtonicu.com/Data/Trials/SPLITSAP.pdf

Nutrition

Nutrition therapy is an essential standard of care for all ICU patients who are mechanically ventilated and remain in ICU for more than a few days. There is a substantial and well established dissociation between the recommended calorie requirement and calories actually delivered to ICU patients. Nevertheless, while it remains logical that energy delivery should match energy consumption, the benefits of such matching remain to be confirmed by a robust, high quality clinical trial.  We are working with Australian investigators who have recently completed a pilot study demonstrating that delivery of full-recommended calorie requirements to mechanically ventilated ICU patients may improve 90-day survival. We are currently seeking funding from the Health Research Council of New Zealand to determine if delivery of the full recommended calorie (energy) requirement to critically ill patients improves 90 day survival when compared to standard practice.

Selective decontamination of the digestive tract

Selective Digestive Decontamination (SDD) consists of a short course of antibiotic and antifungal treatment given to reduce the risk of developing hospital-acquired infection. We have recently received funding from the Health Research Council of New Zealand for the SuDDICU trial.  The SuDDICU trial is a ‘cluster randomised trial’ in which 100 ICUs in four countries, including three ICUs in NZ, will be assigned to use either SDD or standard therapy. As well as establishing whether SDD saves lives, this study will also establish whether SDD changes the numbers of antibiotic-resistant bacteria in the ICU. If the potential benefits of this treatment are realised, the results of this study will have global impact in terms of lives saved and infections prevented as well as potentially allowing large savings in health care spending.

Stress ulcer prophylaxis

The administration of stress ulcer prophylaxis (SUP), either with a Proton Pump Inhibitor (PPI) or a Histamine-2 Receptor Blocker (H₂RB) is recommended in international guidelines and incorporated into quality-oriented checklists for care of ICU patients. Our recent data show that PPIs and H₂RBs are routinely used for SUP in Australia and New Zealand with the choice of medication probably not based on patient factors, but instead dependent on clinician preference or unit policy. This practice variation reflects the lack of definitive evidence comparing PPIs to H₂RBs in the ICU setting. Although data suggest PPIs are more effective at reducing upper GI bleeding risk in ICU patients than H₂RBs, it also appears that using PPIs in ICU patients is associated with a 17-20% increase in pneumonia risk compared to H₂RBs, and that PPI use but not H₂RB use is associated with increased risk of Clostridium difficile infection. The overall influence of the opposing risks of upper GI bleeding and SUP-related infectious complications on in-hospital mortality is unknown.  We are currently seeking funding from the Health Research Council of New Zealand to lead a multicentre, multinational trial comparing the safety and efficacy of PPIs vs. H₂RBs in 40,000 mechanically ventilated ICU patients.