Critical Care - Research Publications

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Pleural drainage: an evolving area.

Kelly, MG (Springer Science and Business Media LLC, 2004-04)
Should central venous catheters be used to drain pleural effusions?

MacDuff, A ; Grant, IS (Springer Science and Business Media LLC, 2004-02)
Continuous haemofiltration in the intensive care unit

Bellomo, R ; Ronco, C (BMC, 2000)

Continuous renal replacement therapy (CRRT) was first described in 1977 for the treatment of diuretic-unresponsive fluid overload in the intensive care unit (ICU). Since that time this treatment has undergone a remarkable technical and conceptual evolution. It is now available in most tertiary ICUs around the world and has almost completely replaced intermittent haemodialysis (IHD) in some countries. Specially made machines are now available, and venovenous therapies that use blood pumps have replaced simpler techniques. Although, it remains controversial whether CRRT decreases mortality when compared with IHD, much evidence suggests that it is physiologically superior. The use of CRRT has also spurred renewed interest in the broader concept of blood purification, particularly in septic states. Experimental evidence suggests that this is a promising approach to the management of septic shock in critically ill patients. The evolution and use of CRRT is likely to continue and grow over the next decade.
Hemofiltration in sepsis: where do we go from here?

Kellum, JA ; Bellomo, R (BMC, 2000)

Hemofiltration as an adjunct to therapy for sepsis is now 10 years old. Despite early successes and significant theoretical advantages, the treatment remains experimental. Although feasibility has been established, efficacy has proved to be much more difficult. Clinical as well as technical difficulties remain important considerations to future studies. These issues are discussed and the brief history of hemofiltration in sepsis is reviewed.
Bench-to-bedside review: Lactate and the kidney

Bellomo, R (BIOMED CENTRAL LTD, 2002-08)

The native kidney has a major role in lactate metabolism. The renal cortex appears to be the major lactate-consuming organ in the body after the liver. Under conditions of exogenous hyperlactatemia, the kidney is responsible for the removal of 25-30% of all infused lactate. Most of such removal is through lactate metabolism rather than excretion, although under conditions of marked hyperlactatemia such excretion can account for approximately 10-12% of renal lactate disposal. Indeed, nephrectomy results in an approximately 30% decrease in exogenous lactate removal. Importantly and differently from the liver, however, the kidney's ability to remove lactate is increased by acidosis. While acidosis inhibits hepatic lactate metabolism, it increases lactate uptake and utilization via gluconeogenesis by stimulating the activity of phospho-enolpyruvate carboxykinase. The kidney remains an effective lactate-removing organ even during endotoxemic shock. The artificial kidney also has a profound effect on lactate balance. If lactate-buffered fluids are used in patients who require continuous hemofiltration and who have pretreatment hyperlactatemia, the serum lactate levels can significantly increase. In some cases, this increase can result in an exacerbation of metabolic acidosis. If bicarbonate-buffered replacement fluids are used, a significant correction of the acidosis or acidemia can also be achieved. The clinician needs to be aware of these renal effects on lactate levels to understand the pathogenesis of hyperlactatemia in critically ill patients, and to avoid misinterpretations and unnecessary or inappropriate diagnostic or therapeutic activities.
Pro/con clinical debate: Is high-volume hemofiltration beneficial in the treatment of septic shock?

Reiter, K ; Bellomo, R ; Ronco, C ; Kellum, JA (BMC, 2002-02)

Although there have been exciting advances in the management of sepsis and septic shock, mortality still remains high. Recent data suggest that high-volume hemofiltration (HVHF) may play a role in these patients. In contrast to the usual rate of hemofiltration, HVHF is felt to be better able to remove the inflammatory mediators associated with sepsis and septic shock. Such an approach is currently incapable of selectively removing specific mediators. This may be a problem when one considers that several mediators may in fact be beneficial. When determining whether HVHF should be instituted in a patient with septic shock, one need remember that its role is far from clear and its usefulness remains the subject of much debate. Although early data is encouraging, it is clear that additional data is required before HVHF becomes standard management. The authors of this pro/con debate, which is based on a clinical scenario, first describe their own position and then respond to their opponent's position.
Is reducing variability of blood glucose the real but hidden target of intensive insulin therapy?

Egi, M ; Bellomo, R ; Reade, MC (BMC, 2009)

Since the first report that intensive insulin therapy reduced mortality in selected surgical critically ill patients, lowering of blood glucose levels has been recommended as a means of improving patient outcomes. In this initial Leuven trial, blood glucose control by protocol using insulin was applied to 98.7% of patients in the intensive group but to only 39.2% (P < 0.0001) of patients in the control group. If appropriately applied, such protocols should decrease both the mean blood glucose concentration and its variability (variation of blood glucose concentration). Thus, it is logically possible that the benefit of intensive insulin therapy in the first Leuven trial was due to a decrease in mean glucose levels, a decrease in their variability, or both. Several recent studies have confirmed significant associations between variability of blood glucose levels and patient outcomes. Decreasing the variability of blood glucose levels might be an important dimension of glucose management, a possible mechanism by which an intensive insulin protocol exerts its putative beneficial effects, and an important goal of glucose management in the intensive care unit. Clinicians need to be aware of this controversy when considering the application of intensive insulin therapy and interpreting future trials.
Effectiveness of the Medical Emergency Team: the importance of dose

Jones, D ; Bellomo, R ; DeVita, MA (BMC, 2009)

Up to 17% of hospital admissions are complicated by serious adverse events unrelated to the patients presenting medical condition. Rapid Response Teams (RRTs) review patients during early phase of deterioration to reduce patient morbidity and mortality. However, reports of the efficacy of these teams are varied. The aims of this article were to explore the concept of RRT dose, to assess whether RRT dose improves patient outcomes, and to assess whether there is evidence that inclusion of a physician in the team impacts on the effectiveness of the team. A review of available literature suggested that the method of reporting RRT utilization rate, (RRT dose) is calls per 1,000 admissions. Hospitals with mature RRTs that report improved patient outcome following RRT introduction have a RRT dose between 25.8 and 56.4 calls per 1,000 admissions. Four studies report an association between increasing RRT dose and reduced in-hospital cardiac arrest rates. Another reported that increasing RRT dose reduced in-hospital mortality for surgical but not medical patients. The MERIT study investigators reported a negative relationship between MET-like activity and the incidence of serious adverse events. Fourteen studies reported improved patient outcome in association with the introduction of a RRT, and 13/14 involved a Physician-led MET. These findings suggest that if the RRT is the major method for reviewing serious adverse events, the dose of RRT activation must be sufficient for the frequency and severity of the problem it is intended to treat. If the RRT dose is too low then it is unlikely to improve patient outcomes. Increasing RRT dose appears to be associated with reduction in cardiac arrests. The majority of studies reporting improved patient outcome in association with the introduction of an RRT involve a MET, suggesting that inclusion of a physician in the team is an important determinant of its effectiveness.
Guidance in sepsis management: navigating uncharted waters?

Reade, MC ; Warrillow, SJ ; Myburgh, JA ; Bellomo, R (BMC, 2008)
The pursuit of a high central venous oxygen saturation in sepsis: growing concerns

Bellomo, R ; Reade, MC ; Warrillow, SJ (BMC, 2008)

In this issue of Critical Care, Dutch investigators report that, in a cohort of patients with sepsis/septic shock admitted to three different intensive care units (ICUs), low central venous oxygen saturation (ScvO2) was uncommon at the time of ICU admission, and hospital mortality was <30%. Their findings, taken together with those of recent reports from Australia and New Zealand (ANZ), raise serious concerns about the utility of early goal directed therapy (EGDT) outside the context of the original trial. Despite inclusion of EGDT into the Surviving Sepsis Guidelines, in response to growing uncertainty, ANZ and US investigators will soon begin randomization of patients into two large multicentre trials comparing EGDT to standard therapy. Until such studies are completed, basing international treatment guidelines on a single centre study performed in what may turn out to be a highly atypical environment would seem premature.

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