Physiological changes after fluid bolus therapy in sepsis: a systematic review of contemporary data

Fluid bolus therapy (FBT) is a standard of care in the management of the septic, hypotensive, tachycardic and/or oliguric patient. However, contemporary evidence for FBT improving patient-centred outcomes is scant. Moreover, its physiological effects in contemporary ICU environments and populations are poorly understood. Using three electronic databases, we identified all studies describing FBT between January 2010 and December 2013. We found 33 studies describing 41 boluses. No randomised controlled trials compared FBT with alternative interventions, such as vasopressors. The median fluid bolus was 500 ml (range 100 to 1,000 ml) administered over 30 minutes (range 10 to 60 minutes) and the most commonly administered fluid was 0.9% sodium chloride solution. In 19 studies, a predetermined physiological trigger initiated FBT. Although 17 studies describe the temporal course of physiological changes after FBT in 31 patient groups, only three studies describe the physiological changes at 60 minutes, and only one study beyond this point. No studies related the physiological changes after FBT with clinically relevant outcomes. There is a clear need for at least obtaining randomised controlled evidence for the physiological effects of FBT in patients with severe sepsis and septic shock beyond the period immediately after its administration

Changes in intravenous fluid use patterns in Australia and New Zealand: evidence of research translating into practice

OBJECTIVES: To describe changes in the use of intravenous (IV) fluid by quantity and type in different regions of Australia and New Zealand. DESIGN, SETTING AND PARTICIPANTS: We conducted a retrospective ecological study examining regional and temporal trends in IV fluid consumption across Australia and New Zealand over the periods 2012-2013 and 2013- 2014, using national proprietary sales data as a surrogate for consumption, and demographic data from the public domain. RESULTS: More than 13.3 million litres of IV fluid were consumed in Australia and New Zealand in 2012-2013, and more than 13.9 million litres in 2013-2014, with colloid solutions accounting for < 2%. There was marked regional variation in consumption of fluids, by volumes and proportions used, when standardised to overall Australian and New Zealand values. There was no significant change in the overall volume of crystalloid solutions consumed but there was a significant decrease (9%; P = 0.02) in the ratio of unbalanced to balanced crystalloid solutions consumed. Consumption of all forms of colloid solutions decreased, with a 12% reduction overall (P = 0.02), primarily driven by a 67% reduction in the consumption of hydroxyethyl starch (HES) solutions. CONCLUSIONS: The amount and type of IV fluid use, as determined by fluid sales, is highly variable across Australia and New Zealand. However, overall use of balanced crystalloid solutions is increasing and the use of HES has decreased dramatically

Acute kidney injury in sepsis

Acute kidney injury (AKI) and sepsis carry consensus definitions. The simultaneous presence of both identifies septic AKI. Septic AKI is the most common AKI syndrome in ICU and accounts for approximately half of all such AKI. Its pathophysiology remains poorly understood, but animal models and lack of histological changes suggest that, at least initially, septic AKI may be a functional phenomenon with combined microvascular shunting and tubular cell stress. The diagnosis remains based on clinical assessment and measurement of urinary output and serum creatinine. However, multiple biomarkers and especially cell cycle arrest biomarkers are gaining acceptance. Prevention of septic AKI remains based on the treatment of sepsis and on early resuscitation. Such resuscitation relies on the judicious use of both fluids and vasoactive drugs. In particular, there is strong evidence that starch-containing fluids are nephrotoxic and decrease renal function and suggestive evidence that chloride-rich fluid may also adversely affect renal function. Vasoactive drugs have variable effects on renal function in septic AKI. At this time, norepinephrine is the dominant agent, but vasopressin may also have a role. Despite supportive therapies, renal function may be temporarily or completely lost. In such patients, renal replacement therapy (RRT) becomes necessary. The optimal intensity of this therapy has been established, while the timing of when to commence RRT is now a focus of investigation. If sepsis resolves, the majority of patients recover renal function. Yet, even a single episode of septic AKI is associated with increased subsequent risk of chronic kidney disease.Peer reviewe

Defining the characteristics and expectations of fluid bolus therapy : A worldwide perspective

Purpose: The purpose of the study is to understand what clinicians believe defines fluid bolus therapy (FBT) and the expected response to such intervention. Methods: We asked intensive care specialists in 30 countries to participate in an electronic questionnaire of their practice, definition, and expectations of FBT. Results: We obtained 3138 responses. Despite much variation, more than 80% of respondents felt that more than 250 mL of either colloid or crystalloid fluid given over less than 30 minutes defined FBT, with crystalloids most acceptable. The most acceptable crystalloid and colloid for use as FBT were 0.9% saline and 4% albumin solution, respectively. Most respondents believed that one or more of the following physiological changes indicates a response to FBT: a mean arterial pressure increase greater than 10 mm Hg, a heart rate decrease greater than 10 beats per minute, an increase in urinary output by more than 10 mL/h, an increase in central venous oxygen saturation greater than 4%, or a lactate decrease greater than 1 mmol/L. Conclusions: Despite wide variability between individuals and countries, clear majority views emerged to describe practice, define FBT, and identify a response to it. Further investigation is now required to describe actual FBT practice and to identify the magnitude and duration of the physiological response to FBT and its relationship to patient-centered outcomes. (C) 2016 Elsevier Inc. All rights reserved.Peer reviewe

Defining the characteristics and expectations of fluid bolus therapy: a worldwide perspective

Purpose: The purpose of the study is to understand what clinicians believe defines fluid bolus therapy (FBT) and the expected response to such intervention. Methods: We asked intensive care specialists in 30 countries to participate in an electronic questionnaire of their practice, definition, and expectations of FBT. Results: We obtained 3138 responses. Despite much variation, more than 80% of respondents felt that more than 250 mL of either colloid or crystalloid fluid given over less than 30 minutes defined FBT, with crystalloids most acceptable. The most acceptable crystalloid and colloid for use as FBT were 0.9% saline and 4% albumin solution, respectively. Most respondents believed that one or more of the following physiological changes indicates a response to FBT: a mean arterial pressure increase greater than 10 mm Hg, a heart rate decrease greater than 10 beats per minute, an increase in urinary output by more than 10 mL/h, an increase in central venous oxygen saturation greater than 4%, or a lactate decrease greater than 1 mmol/L. Conclusions: Despite wide variability between individuals and countries, clear majority views emerged to describe practice, define FBT, and identify a response to it. Further investigation is now required to describe actual FBT practice and to identify the magnitude and duration of the physiological response to FBT and its relationship to patient-centered outcomes.Facultad de Ciencias Médica

The Role of Oliguria and the Absence of Fluid Administration and Balance Information in Illness Severity Scores

Urinary examination has formed part of patient assessment since the earliest days of medicine. Current definitions of oliguria are essentially arbitrary, but duration and intensity of oliguria have been associated with an increased risk of mortality, and this risk is not completely attributable to the development of concomitant acute kidney injury (AKI) as defined by changes in serum creatinine concentration. The increased risk of death associated with the development of AKI itself may be modified by directly or indirectly by progressive fluid accumulation, due to reduced elimination and increased fluid administration. None of the currently extant major illness severity scoring systems or outcome prediction models use modern definitions of AKI or oliguria, or any values representative of fluid volumes variables. Even if a direct relationship with mortality is not observed, then it is possible that fluid balance or fluid volume variables mediate the relationship between illness severity and mortality in the renal and respiratory physiological domains. Fluid administration and fluid balance may then be an important, easily modifiable therapeutic target for future investigation. These relationships require exploration in large datasets before being prospectively validated in groups of critically ill patients from differing jurisdictions to improve prognostication and mortality prediction

The Complexities of Intravenous Fluid Research:Questions of Scale, Volume, and Accumulation

Despite near ubiquity, information regarding fluids consumption at a health care systems level, and patient exposure at an individual level, is surprisingly limited in the medical literature. The epidemiology of the foundational medical intervention of intravenous fluid administration is incredibly complex, with millions of patients being exposed internationally every year. Fluid is being given for different reasons, to different targets, following different triggers, by different specialties in different countries, and any observations that can be made are thought to have limited external validity to other jurisdictions and patient groups. The independent effects of fluid administration and fluid accumulation are very hard to separate from other markers of illness severity and aspects of the process of care. Fluid accumulation can result in organ injury, even when the fluid is being given to purportedly ameliorate or prevent such injury, and if it were independently associated with mortality then would be an easily accessible and modifiable risk factor for subsequent morbidity or death. Despite their ubiquity, it is clear that we have limited understanding of the effects of the intravenous fluids we use daily in the most vulnerable of patient groups. The research agenda in this field is large and urgent

The normal cardiac index in older healthy individuals: a scoping review.

OBJECTIVE Despite the growing number of older patients having major surgery, the normal resting values for the cardiac index of older patients remain unclear. We aim to derive a normative value for such patients. DESIGN Scoping review. DATA SOURCES We searched MEDLINE, EMBASE and CENTRAL for studies reporting measured values of cardiac output or cardiac index in healthy, older humans at rest. RESULTS We retrieved 5340 citations and assessed 412 fulltext articles for eligibility. Twenty-nine studies, published between 1964 and 2017, met our inclusion criteria. Overall, the mean cardiac index in healthy volunteers over 60 years of age was reported between 2.1 and 3.2 L/min/m and the mean cardiac output was between 3.1 and 6.4 L/min. A yearly decline in cardiac index (between 3.5 and 8 mL/min/m per year) was reported in some but not all studies. Only one study measured the cardiac index in nine people over 80 years of age. CONCLUSIONS The normal range of the cardiac index in older patients may be lower than previously reported. Its rate of decline with age is uncertain, but likely between 3.5 and 8 mL/min/m per year. Data on the normal cardiac index in people older than 80 years are scant

Plasma endostatin may improve acute kidney injury risk prediction in critically ill patients

BACKGROUND: Breakdown of renal endothelial, tubular and glomerular matrix collagen plays a major role in acute kidney injury (AKI) development. Such collagen breakdown releases endostatin into the circulation. The aim of this study was to compare the AKI predictive value of plasma endostatin with two previously suggested biomarkers of AKI, cystatin C and neutrophil gelatinase-associated lipocalin (NGAL). METHODS: We studied 93 patients without kidney disease who had a first plasma sample obtained within 48 h of ICU admission. We identified risk factors for AKI within the population and designed a predictive model. The individual ability and net contribution of endostatin, cystatin C and NGAL to predict AKI were evaluated by the area under the receiver operating characteristics curve (AUC), likelihood-ratio test, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: In total, 21 (23 %) patients experienced AKI within 72 h. A three-parameter model (age, illness severity score and early oliguria) predicted AKI with an AUC of 0.759 (95 % CI 0.646-0.872). Adding endostatin to the predictive model significantly (P = 0.04) improved the AUC to 0.839 (95 % CI 0.752-0.925). In addition, endostatin significantly improved risk prediction using the likelihood-ratio test (P = 0.005), NRI analysis (0.27; P = 0.04) and IDI analysis (0.07; P = 0.04). In contrast, adding cystatin C or NGAL to the three-parameter model did not improve risk prediction in any of the four analyses. CONCLUSIONS: In this cohort of critically ill patients, plasma endostatin improved AKI prediction based on clinical risk factors, while cystatin C and NGAL did not