There is a paucity of high-quality evidence to guide clinicians on thresholds for commencement of... more There is a paucity of high-quality evidence to guide clinicians on thresholds for commencement of renal replacement therapy (RRT) in critically ill patients with acute kidney injury (AKI), and wide international practice variation. Wald et al. report a pilot randomized trial examining accelerated use of RRT for moderate AKI in the intensive care unit, providing a workable design for a definitive trial examining the timing of RRT in critical illness.
ABSTRACT Compared to other organ systems, diagnostic criteria for acute kidney injury (AKI) using... more ABSTRACT Compared to other organ systems, diagnostic criteria for acute kidney injury (AKI) using serum creatinine and urine output are well established [1]. Despite this, there is little evidence to support any specific interventions to improve outcomes after AKI diagnosis. Delayed and imprecise identification of early AKI by conventional diagnostic criteria may explain these failures. Consequently, numerous plasma and urinary biomarkers for renal injury or renal dysfunction have been the subject of intense study for well over 10 years with the aim of earlier and more precise recognition of incipient AKI [2]. Despite this activity, only a few AKI biomarkers have been commercially marketed for clinical use. The most well-known plasma or urinary neutrophil gelatinase-associated lipocalin (NGAL) [3] has been available for over 5 years, but has failed to demonstrate clear clinical utility [4-6] or gain widespread uptake in the ICU. More recently, a promising combination of two cell cycle arrest ma ...
ABSTRACT Presepsin—soluble CD14 (sCD14)—has attracted significant attention from several clinical... more ABSTRACT Presepsin—soluble CD14 (sCD14)—has attracted significant attention from several clinical research groups recently as a prognostic biomarker in sepsis. In a recent issue of Intensive Care Medicine, Masson and colleagues analyzed a subset of data from the ALBIOS trial to explore the potential of sCD14 as a biomarker in sepsis [1]. In this ALBIOS sub-study, these authors examined the prognostic significance of sCD14 measured at enrollment and on days 2 and 7 in 997 critically ill patients with sepsis, adding to a burgeoning body of published studies examining the relationship between sCD14 and the presence [2] or severity [3, 4] of sepsis.Notable contributions made by this sub-study relate to three main findings. First, higher baseline sCD14 level was associated with both the severity and number of organs demonstrating dysfunction—both initially and over time. In multivariable analysis, higher sCD14 levels were most strongly correlated with renal and liver dysfunction. sCD14 is a 13-kDa p ...
very little to the analysis. With regard to Norwood et al (4), the study reported a 0% prevalence... more very little to the analysis. With regard to Norwood et al (4), the study reported a 0% prevalence of bacteremia associated with positive subcutaneous catheter results, and the overall weighting of this study in our pooled risk estimate was 1.00%, which is also a very small contribution. In keeping with our results, we believe that whenever possible, the radial route should be preferred over a femoral arterial route as recommended in the most recent Healthcare Infection Control Practices Advisory Committee guidelines for prevention of central catheter-associated bloodstream infection (5). We agree that given improved care in insertion and maintenance over the years, the overall risk may be reduced considerably, as was demonstrated for central venous catheters (6) and as Lee et al show in their sensitivity analysis for arterial catheters.
ABSTRACT The rationale for perioperative fluid therapy has been to preserve organ perfusion. Howe... more ABSTRACT The rationale for perioperative fluid therapy has been to preserve organ perfusion. However, conservative postoperative fluid balance (FB) is now encouraged to avoid the effects of iatrogenic fluid overload. In addition, fluid expansion has been described as a confounder of acute kidney injury (AKI) diagnosis by dilution serum creatinine (SCr). We conducted a prospective audit of FB and renal function in patients undergoing major elective surgery admitted to critical care over a 28-day period. Thirty-two patients were studied over a median of 3 critical care days. We achieved near-neutral fluid balances after admission, but did not resolve intraoperative fluid accumulation. SCr fell significantly, even after there was no further net fluid accumulation. This suggests a decrease in creatinine production after major surgery, rather than fluid expansion, may largely account for sCr decreases in these patients.
In critical illness, septic shock is a contributing factor in nearly half of all cases of acute k... more In critical illness, septic shock is a contributing factor in nearly half of all cases of acute kidney injury (AKI). Traditional approaches to prevention of organ dysfunction in early sepsis have focused on prevention of hypoperfusion by optimisation of systemic haemodynamics, primarily by fluid resuscitation. Fluid administration to a target central venous pressure (CVP) of 8 to 12 mmHg (12 to 15 mmHg in mechanically ventilated patients) is currently recommended for the early resuscitation of septic shock. However, in the previous issue of Critical Care, Legrand and colleagues report that higher CVP in the first 24 hours of ICU admission with septic shock was associated with increased risk for development or persistence of AKI over the next 5 days. This study highlights a potential association between venous congestion and the development of septic AKI, suggesting that CVP-targeted fluid resuscitation in septic shock might not be beneficial for renal function.
In their interesting observational study Smith and Perner [1] describe fl uid resuscitation (FR) ... more In their interesting observational study Smith and Perner [1] describe fl uid resuscitation (FR) in 164 patients with septic shock, concluding that survival was better in patients receiving higher volumes over the fi rst 72 h. I think we should be cautious, however, to conclude from this that more is better.
Changing epidemiology of acute kidney injury (AKI) in adults and children has resulted in more pa... more Changing epidemiology of acute kidney injury (AKI) in adults and children has resulted in more patients being treated for kidney injury occurring in the context of multi--organ failure requiring treatment in the intensive care unit (ICU). AKI complicating critical illness has complex, multi--factorial etiology and supportive care, including organ support, remains the mainstay of therapy. In the day--to--day management of AKI in the ICU two of the major challenges are the inadequacy of current diagnostics for the early identification of AKI, and the relationship between hemodynamic resuscitation strategies and the development of AKI. This review focuses on these areas from the intensivist's perspective. Given that diagnosis of AKI is often delayed, prevention of complications and limitation of secondary renal injury is of particular importance. Fluid overload is increasingly being associated with adverse patient outcomes in critical illness and may contribute to persistent renal dysfunction. Thus hemodynamic management strategies in AKI should be tailored to limit fluid overload as much as possible.
Traditionally, renal ischemia has been regarded as central to the pathogenesis of sepsis-associat... more Traditionally, renal ischemia has been regarded as central to the pathogenesis of sepsis-associated acute kidney injury (SA-AKI). Accordingly, hemodynamic management of SA-AKI has emphasized restoration of renal perfusion, whereas, experimentally, ischemia reperfusion models have been emphasized. However, in human beings, SA-AKI usually is accompanied by hyperdynamic circulation. Moreover, clinical and experimental evidence now suggests the importance of inflammatory mechanisms in the development of AKI and microcirculatory dysfunction more than systemic alteration in renal perfusion. In this review, we examine systemic, regional, and microcirculatory hemodynamics in SA-AKI, and attempt to rationalize the hemodynamic management of this condition.
The Acute Dialysis Quality Initiative (ADQI) dedicated its Twelfth Consensus Conference (2013) to... more The Acute Dialysis Quality Initiative (ADQI) dedicated its Twelfth Consensus Conference (2013) to all aspects of fluid therapy, including the management of fluid overload (FO). The aim of the working subgroup 'Mechanical fluid removal' was to review the indications, prescription, and management of mechanical fluid removal within the broad context of fluid management of critically ill patients. The working group developed a list of preliminary questions and objectives and performed a modified Delphi analysis of the existing literature. Relevant studies were identified through a literature search using the MEDLINE database and bibliographies of relevant research and review articles. After review of the existing literature, the group agreed the following consensus statements: (i) in critically ill patients with FO and with failure of or inadequate response to pharmacological therapy, mechanical fluid removal should be considered as a therapy to optimize fluid balance. (ii) When...
Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are significantly ass... more Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are significantly associated with morbidity and mortality. We performed a prospective observational study and applied recently published consensus criteria to measure and describe the incidence of IAH and ACS, identify risk factors for their development and define their association with outcomes. We studied 100 consecutive patients admitted to our general intensive care unit. We recorded relevant demographic, clinical data and maximal (max) and mean intra-abdominal pressure (IAP). We measured and defined IAH and ACS using consensus guidelines. Of our study patients, 42% (by IAPmax) and 38% (by IAPmean) had IAH. Patients with IAH had greater mean body mass index (30.4 ± 9.6 vs 25.4 ± 5.6 kg/m(2), P=0.005), Acute Physiology and Chronic Health Evaluation III score (78.2 ± 28.5 vs 65.5 ± 29.2, P=0.03) and central venous pressure (12.8 ± 4.8 vs 9.2 ± 3.5 mmHg, P <0.001), lower abdominal perfusion pressure (67....
There is a paucity of high-quality evidence to guide clinicians on thresholds for commencement of... more There is a paucity of high-quality evidence to guide clinicians on thresholds for commencement of renal replacement therapy (RRT) in critically ill patients with acute kidney injury (AKI), and wide international practice variation. Wald et al. report a pilot randomized trial examining accelerated use of RRT for moderate AKI in the intensive care unit, providing a workable design for a definitive trial examining the timing of RRT in critical illness.
ABSTRACT Compared to other organ systems, diagnostic criteria for acute kidney injury (AKI) using... more ABSTRACT Compared to other organ systems, diagnostic criteria for acute kidney injury (AKI) using serum creatinine and urine output are well established [1]. Despite this, there is little evidence to support any specific interventions to improve outcomes after AKI diagnosis. Delayed and imprecise identification of early AKI by conventional diagnostic criteria may explain these failures. Consequently, numerous plasma and urinary biomarkers for renal injury or renal dysfunction have been the subject of intense study for well over 10 years with the aim of earlier and more precise recognition of incipient AKI [2]. Despite this activity, only a few AKI biomarkers have been commercially marketed for clinical use. The most well-known plasma or urinary neutrophil gelatinase-associated lipocalin (NGAL) [3] has been available for over 5 years, but has failed to demonstrate clear clinical utility [4-6] or gain widespread uptake in the ICU. More recently, a promising combination of two cell cycle arrest ma ...
ABSTRACT Presepsin—soluble CD14 (sCD14)—has attracted significant attention from several clinical... more ABSTRACT Presepsin—soluble CD14 (sCD14)—has attracted significant attention from several clinical research groups recently as a prognostic biomarker in sepsis. In a recent issue of Intensive Care Medicine, Masson and colleagues analyzed a subset of data from the ALBIOS trial to explore the potential of sCD14 as a biomarker in sepsis [1]. In this ALBIOS sub-study, these authors examined the prognostic significance of sCD14 measured at enrollment and on days 2 and 7 in 997 critically ill patients with sepsis, adding to a burgeoning body of published studies examining the relationship between sCD14 and the presence [2] or severity [3, 4] of sepsis.Notable contributions made by this sub-study relate to three main findings. First, higher baseline sCD14 level was associated with both the severity and number of organs demonstrating dysfunction—both initially and over time. In multivariable analysis, higher sCD14 levels were most strongly correlated with renal and liver dysfunction. sCD14 is a 13-kDa p ...
very little to the analysis. With regard to Norwood et al (4), the study reported a 0% prevalence... more very little to the analysis. With regard to Norwood et al (4), the study reported a 0% prevalence of bacteremia associated with positive subcutaneous catheter results, and the overall weighting of this study in our pooled risk estimate was 1.00%, which is also a very small contribution. In keeping with our results, we believe that whenever possible, the radial route should be preferred over a femoral arterial route as recommended in the most recent Healthcare Infection Control Practices Advisory Committee guidelines for prevention of central catheter-associated bloodstream infection (5). We agree that given improved care in insertion and maintenance over the years, the overall risk may be reduced considerably, as was demonstrated for central venous catheters (6) and as Lee et al show in their sensitivity analysis for arterial catheters.
ABSTRACT The rationale for perioperative fluid therapy has been to preserve organ perfusion. Howe... more ABSTRACT The rationale for perioperative fluid therapy has been to preserve organ perfusion. However, conservative postoperative fluid balance (FB) is now encouraged to avoid the effects of iatrogenic fluid overload. In addition, fluid expansion has been described as a confounder of acute kidney injury (AKI) diagnosis by dilution serum creatinine (SCr). We conducted a prospective audit of FB and renal function in patients undergoing major elective surgery admitted to critical care over a 28-day period. Thirty-two patients were studied over a median of 3 critical care days. We achieved near-neutral fluid balances after admission, but did not resolve intraoperative fluid accumulation. SCr fell significantly, even after there was no further net fluid accumulation. This suggests a decrease in creatinine production after major surgery, rather than fluid expansion, may largely account for sCr decreases in these patients.
In critical illness, septic shock is a contributing factor in nearly half of all cases of acute k... more In critical illness, septic shock is a contributing factor in nearly half of all cases of acute kidney injury (AKI). Traditional approaches to prevention of organ dysfunction in early sepsis have focused on prevention of hypoperfusion by optimisation of systemic haemodynamics, primarily by fluid resuscitation. Fluid administration to a target central venous pressure (CVP) of 8 to 12 mmHg (12 to 15 mmHg in mechanically ventilated patients) is currently recommended for the early resuscitation of septic shock. However, in the previous issue of Critical Care, Legrand and colleagues report that higher CVP in the first 24 hours of ICU admission with septic shock was associated with increased risk for development or persistence of AKI over the next 5 days. This study highlights a potential association between venous congestion and the development of septic AKI, suggesting that CVP-targeted fluid resuscitation in septic shock might not be beneficial for renal function.
In their interesting observational study Smith and Perner [1] describe fl uid resuscitation (FR) ... more In their interesting observational study Smith and Perner [1] describe fl uid resuscitation (FR) in 164 patients with septic shock, concluding that survival was better in patients receiving higher volumes over the fi rst 72 h. I think we should be cautious, however, to conclude from this that more is better.
Changing epidemiology of acute kidney injury (AKI) in adults and children has resulted in more pa... more Changing epidemiology of acute kidney injury (AKI) in adults and children has resulted in more patients being treated for kidney injury occurring in the context of multi--organ failure requiring treatment in the intensive care unit (ICU). AKI complicating critical illness has complex, multi--factorial etiology and supportive care, including organ support, remains the mainstay of therapy. In the day--to--day management of AKI in the ICU two of the major challenges are the inadequacy of current diagnostics for the early identification of AKI, and the relationship between hemodynamic resuscitation strategies and the development of AKI. This review focuses on these areas from the intensivist's perspective. Given that diagnosis of AKI is often delayed, prevention of complications and limitation of secondary renal injury is of particular importance. Fluid overload is increasingly being associated with adverse patient outcomes in critical illness and may contribute to persistent renal dysfunction. Thus hemodynamic management strategies in AKI should be tailored to limit fluid overload as much as possible.
Traditionally, renal ischemia has been regarded as central to the pathogenesis of sepsis-associat... more Traditionally, renal ischemia has been regarded as central to the pathogenesis of sepsis-associated acute kidney injury (SA-AKI). Accordingly, hemodynamic management of SA-AKI has emphasized restoration of renal perfusion, whereas, experimentally, ischemia reperfusion models have been emphasized. However, in human beings, SA-AKI usually is accompanied by hyperdynamic circulation. Moreover, clinical and experimental evidence now suggests the importance of inflammatory mechanisms in the development of AKI and microcirculatory dysfunction more than systemic alteration in renal perfusion. In this review, we examine systemic, regional, and microcirculatory hemodynamics in SA-AKI, and attempt to rationalize the hemodynamic management of this condition.
The Acute Dialysis Quality Initiative (ADQI) dedicated its Twelfth Consensus Conference (2013) to... more The Acute Dialysis Quality Initiative (ADQI) dedicated its Twelfth Consensus Conference (2013) to all aspects of fluid therapy, including the management of fluid overload (FO). The aim of the working subgroup 'Mechanical fluid removal' was to review the indications, prescription, and management of mechanical fluid removal within the broad context of fluid management of critically ill patients. The working group developed a list of preliminary questions and objectives and performed a modified Delphi analysis of the existing literature. Relevant studies were identified through a literature search using the MEDLINE database and bibliographies of relevant research and review articles. After review of the existing literature, the group agreed the following consensus statements: (i) in critically ill patients with FO and with failure of or inadequate response to pharmacological therapy, mechanical fluid removal should be considered as a therapy to optimize fluid balance. (ii) When...
Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are significantly ass... more Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are significantly associated with morbidity and mortality. We performed a prospective observational study and applied recently published consensus criteria to measure and describe the incidence of IAH and ACS, identify risk factors for their development and define their association with outcomes. We studied 100 consecutive patients admitted to our general intensive care unit. We recorded relevant demographic, clinical data and maximal (max) and mean intra-abdominal pressure (IAP). We measured and defined IAH and ACS using consensus guidelines. Of our study patients, 42% (by IAPmax) and 38% (by IAPmean) had IAH. Patients with IAH had greater mean body mass index (30.4 ± 9.6 vs 25.4 ± 5.6 kg/m(2), P=0.005), Acute Physiology and Chronic Health Evaluation III score (78.2 ± 28.5 vs 65.5 ± 29.2, P=0.03) and central venous pressure (12.8 ± 4.8 vs 9.2 ± 3.5 mmHg, P <0.001), lower abdominal perfusion pressure (67....
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Papers by John R Prowle