Choice of Fluid- John Myburgh Summary.

 November 11

by Jonathan Downham

Fluid resuscitation in acute medicine: what is the current situation? 

Journal of internal medicine (Accepted Article)

Professor John A Myburgh AO, is Director of the Division of Critical Care and Trauma at the George Institute for Global Health, Professor of Critical Care at the Faculty of Medicine, University of New South Wales and senior intensive care physician at the St George Hospital, Sydney. He holds honorary professorial appointments at University of Sydney and Monash University School of Public Health.

This is a quick summary of some of the key points he makes in the review paper  above. Its a nice summary of some of the issues with some of the papers which direct current opinion.

Before you read the summary it is important to know that he finishes this paper by saying:

“There is increasing evidence that the types of fluid and the manner in which they are administered independently affect patient outcomes. There is little doubt that resuscitation fluids are life-saving in patients with severe, symptomatic hypovolaemia; however, subsequent use of these fluids during the course of critical illness requires the same consideration and care that would be employed for the use of a potentially toxic drug.”

[accordion id=”my-accordion”] [accordion_item parent_id=”my-accordion” title=”Albumin” open=”true”]

Human albumin administration in critically ill patients: systematic review of randomised controlled trials. Cochrane 1998.

“The group concluded that the administration of albumin was associated with a  statistically significant 6% increase in mortality [relative risk (RR) 1.68, 95% confidence interval (CI)  1.28 to 2.23]. The findings of this analysis caused considerable alarm in regions in which albumin was widely used for resuscitation, such as the UK, and resulted in a sharp decline in the use of albumin.”

A Comparison of Albumin and Saline for Fluid  Resuscitation in the Intensive Care Unit. SAFE Sudy. NEJM 2004

“The SAFE study demonstrated no difference in 28-day mortality between patients resuscitated in the  ICU with albumin or saline (RR 0.99, 95% CI 0.91 to 1.09, P = 0.87), thereby refuting the conclusions of the 1998 Cochrane review”

“Among patients with a diagnosis of sepsis, a significant reduction in the adjusted risk of death at 28 days was demonstrated in those who received albumin compared to those treated with saline (odds ratio 0.71, 95% CI 0.52 to 0.97, P = 0.03). This finding suggests that there may be a beneficial effect of albumin in this patient population.”

Albumin replacement in patients with severe sepsis or septic shock. ALBIOS  NEJM 2014

“the administration of concentrated albumin as a drug infusion rather than as a resuscitation fluid to maintain a serum albumin level >30 g/L was compared to the use of crystalloids alone in patients with severe sepsis. No statistically significant
difference in 28-day mortality between the two groups was demonstrated (RR 0.94; 95% CI 0.85 to 1.05, P = 0.29), although there was a significant reduction in mortality in the subgroup of patients with septic shock at enrolment.”

“The findings of the SAFE and ALBIOS studies suggest a potential beneficial effect of albumin for resuscitation of patients with sepsis during the initial admission period to the ICU. However, at present, this remains the only evidence-based indication for albumin.”


[accordion_item parent_id=”my-accordion” title=”Hydroxyethyl Starch”]

Hydroxyethyl Starch or Saline for Fluid Resuscitation in Intensive Care. CHEST study NEJM 2012

Hydroxyethyl Starch 130/0.42 versus Ringer’s Acetate in Severe Sepsis 6S Study NEJM 2012

“In CHEST, no significant difference in 90-day mortality between patients who received either 6% HES (130/0.4) or saline for fluid resuscitation was found (18% vs. 17%; RR 1.06; 95% CI 0.96 to 1.18; P = 0.26). However, the use of HES was associated with a significant increase in the requirement for renal replacement therapy (RR 1.21; 95% CI 1.00 to 1.45, P = 0.04).”

“The 6S study demonstrated a significant increase in 90-day mortality in the 6% HES group compared with the group treated with Ringer’s acetate alone (51% vs. 43%; RR 1.17; 95% CI 1.01 to 1.30; P = 0.03) and a significant increase in the use of renal replacement therapy (RR 1.35; 95% CI 1.01 to 1.80; P = 0.04).”

“Based on the currently available high-quality evidence, the use of HES for resuscitation provides no clinical benefit and is associated with the development of general, dose-dependent nephrotoxicity, adverse events and increased costs. It is therefore difficult to justify its use in any
patient population.”


[accordion_item parent_id=”my-accordion” title=”Crystalloids”]

“There is increasing concern about the effects of hyperchloraemic metabolic acidosis induced by large volumes of saline. The clinical consequences of this phenomenon are unclear but the findings of both animal and human volunteer studies have suggested that they may be due to the development of acute kidney injury.”

The Effect of Different Crystalloid Solutions on Acid-Base Balance and Early Kidney Function After Kidney Transplantation. Anesth  Analg 2008

Extracellular acidosis and the immune response: clinical and physiologic implications. Critical Care 2004

“Saline is associated with a significant increase in mortality and use of renal replacement therapy in patients in ICU  and in those with sepsis, as well as a significant increase in major complications in patients undergoing surgery.”

Association Between a Chloride-Liberal vs Chloride-Restrictive Intravenous Fluid Administration Strategy and Kidney Injury
in Critically Ill Adults. JAMA 2012

Association between the choice of IV crystalloid and in-hospital mortality among critically ill adults with sepsis. Crit Care Med 2014

Major complications, mortality, and resource utilization after open abdominal surgery: 0.9% saline compared to Plasma-Lyte. ANN Surg. 2012

“Although crystalloids are increasingly being recommended and used in daily clinical practice, there is a need to conduct a large-scale, high-quality, randomised controlled trial to determine the efficacy, safety and effects on patient outcomes of saline compared to proprietary preparations of balanced salt solutions.”


[accordion_item parent_id=”my-accordion” title=”Dose and Timing”]

“Resuscitation of patients in shock has been described in four conceptual phases: an initial ‘salvage’ phase in which the priority is life-saving measures to restore vital organ perfusion; an ‘optimisation’ phase to maintain the restored circulation; a ‘stabilisation’ phase to prevent organ dysfunction following haemodynamic stabilisation; and a ‘de-escalation’ phase in which support is weaned and intrinsic haemodynamic function is restored.”

Salvage 0-24 hours

“An initial fluid ‘challenge’ or bolus of crystalloid is recommended in doses of 20–30 mL/kg, primarily as a treatment for hypovolaemia. Evidence to support the use of this dose is limited, and is based on consensus statements and treatment guidelines.”

Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012

“The FEAST study, conducted in febrile children with compensated hypotension living in resource-limited settings, demonstrated
that bolus resuscitation with albumin or saline was not associated with a difference in death at 48 h, but that bolus resuscitation was associated with a significant increase in death at 48 h compared to no fluid administration (RR 1.45, 95% CI 1.13 to 1.86, P = 0.003).”

Exploring mechanisms of excess mortality with early fluid resuscitation: insights from the FEAST trial. BMC Medicine 2013

Optimisation 24-72 hours

“The overall net effect of the administration of unnecessary and ineffective volumes is not improvement in systemic haemodynamic function, but an increase in cumulative fluid balance and pathological, iatrogenic interstitial oedema.”

“The adverse effects of increased fluid balance and the long-term outcomes, particularly increased mortality and prolongation of mechanical ventilation, have been demonstrated in patients with sepsis and the acute respiratory distress syndrome (ARDS). ”

Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Crit Care Med 2011

Comparison of Two Fluid-Management Strategies in Acute Lung Injury NEJM 2006

Stabilisation 72-96 hours.

“It is during this period that unnecessary fluid administration, particularly ‘maintenance’ fluids and administration for drug infusions, substantially contributes to cumulative fluid balance.”

“There is increasing debate about introducing ‘restrictive’ fluid strategies to reduce and minimise cumulative fluid balance, with some evidence that these approaches are effective in reducing morbidity in surgical patients”


“The priority during the de-escalation or ‘de-resuscitation’ phase, usually after 96 h or when haemodynamic stability has returned, is to achieve a negative fluid balance either by restricting intravenous fluid administration or by increasing fluid removal through spontaneous or induced diuresis.”

“There appears to be a changing paradigm to the use of fluids in a more restrictive manner. Such a strategy needs to be carefully evaluated and a definitive randomised controlled trial of restrictive versus liberal fluid strategies should be conducted in critically ill patients to address this fundamental issue.”

Which goal for fluid therapy during colorectal surgery is followed by the best outcome: near-maximal stroke volume or zero fluid balance? Br J Anaesth 2012



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