**4. Delivering fluid therapy**

Following an evidence-informed choice of fluid, the next set of decisions will be equally crucial: how to administer the fluid, how to measure the patient's response to the fluid, and how much fluid should be given. Strategizing intravenous fluid delivery to an acute patient should include a well thought-out plan for these three important elements.

#### **4.1. Resuscitation and the fluid challenge**

A key aim of the fluid resuscitation in the acute setting is to exert a hemodynamic impact, increasing the venous return and the stroke volume. To achieve this, the concept of fluid challenge or fluid bolus was introduced almost four decades ago [57, 58]. The fluid challenge is a targeted administration approach through the delivery of a small amount of fluid over a short period of time, with an assessment of the fluid responsiveness [59].

The administration of fluid challenge has been one of the most diverse practices in fluid therapy. Recent attempts at identifying the global patterns in fluid challenge have provided valuable information. A global inception cohort study on fluid challenge involving 2213 patients across ICUs in 46 countries revealed a median amount of fluid challenge volume of 500 ml, a median time of 24 min, a median rate of fluid administration of 1000 ml/h, and a predominant choice of crystalloids [60]. Interestingly, categorizing patients as fluid responsive, non-fluid responsive, or uncertain fluid responsive did not make any difference to the receipt of further fluid administration in this study. In another study on the worldwide fluid challenge practices, involving 3138 intensive care specialists from 30 countries, more than 80% respondents defined the fluid bolus therapy as delivery of more than 250 mL of either colloid or crystalloid fluid over less than 30 minutes, with crystalloids the most acceptable [61]. These numbers only reflect the majority views on the fluid challenge and must be interpreted in the context of the other aspects of an acute fluid strategy—the fluid responsiveness and the fluid balance.

#### **4.2. Fluid responsiveness**

infused during resuscitation. However, data from recent large multicenter trials on the use of different types of colloids suggested a smaller colloid: crystalloid ratio, between 1:1.1 and 1:1.6 [46–49]. The finding of smaller volume effect advantage from colloid than previously thought adds to the predominant concern on the use of colloid—its effects on the kidney.

Strong evidence emerged in the last decade demonstrating a significant association between the risk of renal dysfunction, measured as AKI, and the need for renal replacement therapy, with the use of hydroxyethyl starch in the acute population of sepsis and intensive care [46, 47]. There are also doubts from observational data on the renal safety of another choice of colloid, the gelatins, in the septic population [50, 51]. The hyperoncotic albumin solutions (20–25%), on the other hand, have been associated with increased risk of renal events when used in cardiac

Besides these renal effects, colloids are more expensive than crystalloids, and there has been an absence of their clinical superiority over crystalloids in the mortality outcome of studies on different acute populations [49, 54, 55]. All these lead to the call for caution in the use of colloids. The recent Surviving Sepsis Guidelines, for example, strongly recommend against the use of hydroxyethyl starches and place albumin and gelatins as a second choice to crystalloids

Following an evidence-informed choice of fluid, the next set of decisions will be equally crucial: how to administer the fluid, how to measure the patient's response to the fluid, and how much fluid should be given. Strategizing intravenous fluid delivery to an acute patient should

A key aim of the fluid resuscitation in the acute setting is to exert a hemodynamic impact, increasing the venous return and the stroke volume. To achieve this, the concept of fluid challenge or fluid bolus was introduced almost four decades ago [57, 58]. The fluid challenge is a targeted administration approach through the delivery of a small amount of fluid over a short

The administration of fluid challenge has been one of the most diverse practices in fluid therapy. Recent attempts at identifying the global patterns in fluid challenge have provided valuable information. A global inception cohort study on fluid challenge involving 2213 patients across ICUs in 46 countries revealed a median amount of fluid challenge volume of 500 ml, a median time of 24 min, a median rate of fluid administration of 1000 ml/h, and a predominant choice of crystalloids [60]. Interestingly, categorizing patients as fluid responsive, non-fluid responsive, or uncertain fluid responsive did not make any difference to the receipt of further fluid administration in this study. In another study on the worldwide fluid challenge practices, involving 3138 intensive care specialists from 30 countries, more than 80% respondents

include a well thought-out plan for these three important elements.

period of time, with an assessment of the fluid responsiveness [59].

surgery [52] and in patients in shock [53].

46 Essentials of Accident and Emergency Medicine

in sepsis fluid resuscitation [56].

**4. Delivering fluid therapy**

**4.1. Resuscitation and the fluid challenge**

Clinical assessment is always an integral component of any fluid therapy approach. Identifying body volume repletion and the likelihood to respond to fluid resuscitation should begin with the background history and elicitation of signs of volume deficits, from the peripheral temperature gradient and capillary refill time [62] to the tachycardia, decreased mean arterial pressure, and oliguria. However, reliance on these clinical signs alone for assessment of volume status and responsiveness could be misleading [63–65]. For instance, an increase in the mean arterial pressure following a fluid challenge could be a result of the changes in the arterial vascular tone rather than a true increase in cardiac output.

Beyond clinical signs, the indices of fluid responsiveness—both static and dynamic—have been extensively studied. The static index of central venous pressure (CVP), arguably the most commonly used measure of fluid responsiveness, has long been shown to have no meaningful relationship to fluid volume and should be abandoned [66]. Similarly, the more invasive static index measurement of pulmonary artery occlusion pressure (PAOP) has its limitations and does not predict fluid responsiveness [67, 68].

The dynamic indices of fluid responsiveness work on the basis of inducing a change in preload and following up the effects on stroke volume and cardiac output [69]. There are different versions of these dynamic measurements with many evolving around the respiratory variation of hemodynamic indices. Examples include the pulse pressure variation (PPV), the pulse contour-derived stroke volume, the inferior vena cava (IVC) parameters assessed by ultrasonography, and the descending aortic blood flow assessed by esophageal Doppler [70–75]. There are, however, limitations to the observations of these respiratory variations. Some of these are of practical significance, like the need for tidal volumes of >7 ml/kg, the absence of spontaneous ventilatory efforts, and the absence of arrhythmia.

An approach to assessment of fluid responsiveness that is not affected by the practical ventilatory limitations above is the passive leg raising, PLR [76]. The postural change in PLR transfers around 300 mL of venous blood from the lower body to the heart. The advantage of this is it is an endogenous fluid challenge that is rapidly reversible [77]. To date, the PLR has been deemed as the most reliable measure of fluid responsiveness [78], although an increase in the intra-abdominal pressure or pain could give a false-negative result [79].

It is important to recognize that fluid responsiveness does not necessarily mean that fluid challenges must be given. It also does not mean that patients should be receiving fluid challenges until they are no longer fluid responsive. The hemodynamic benefits of the fluid boluses should be weighed against the risks of accumulating positive fluid balance, with a strong consideration of the use of vasopressors like noradrenaline to improve organ perfusion [80].

#### **4.3. The importance of fluid balance**

Fluid accumulation in the acute setting is a frequent event. While everything is geared toward early and aggressive fluid resuscitation, as it should be, less emphasis is given toward the risks associated with fluid accumulation and overload. As fluid overload is shown to contribute to poorer outcomes in different acute populations [81–84], it becomes imperative to achieve the right balance between overcoming hypovolemia and organ hypoperfusion and avoiding the dangers of fluid overload [85].

**Author details**

Nor'azim Mohd Yunos

Johor Bahru, Malaysia

DOI: 10.1136/bmj.b2418

c2013-0-13529-5

annurev.bioeng.9.060906.151959

**References**

Address all correspondence to: nor.azim@monash.edu

org.uk/guidance/cg174 [Accessed: 2018-01-03]

2001;**20**:125-130. DOI: 10.1054/clnu.2000.0154

Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia,

[1] National Institute for Health and Care Excellence. Intravenous Fluid Therapy in Adults in Hospital: Clinical Guideline. London: NICE, 2013. Available from: https://www.nice.

Approach to Fluid Therapy in the Acute Setting http://dx.doi.org/10.5772/intechopen.74458 49

[2] Liu B, Finfer S. Intravenous fluids in adults undergoing surgery. BMJ. 2009;**338**:b2418.

[3] Lobo DN, Dube MG, Neal KR, Simpson JS, Rowlands BJ, Allison SP. Problems with solutions: Drowning in the brine of an inadequate knowledge base. Clinical Nutrition.

[4] Costanzo LS. Physiology. 5th ed. Philadelphia, PA: Elsevier; 2014. ISBN: 9781455708475 [5] Kamel KS, Halperin ML. Fluid, Electrolyte, and Acid-Base Physiology: A Problem-Based Approach. 5th ed. Philadelphia, PA: Elsevier; 2017. ISBN 9780323355155. DOI: 10.1016/

[6] Story DA, Morimatsu H, Egi M, Bellomo R. The effect of albumin concentration on plasma sodium and chloride measurements in critically ill patients. Anesthesia and

[7] Macafee DA, Allison SP, Lobo DN. Some interactions between gastrointestinal function and fluid and electrolyte homeostasis. Current Opinion in Clinical Nutrition and Meta-

[8] Starling EH. On the absorption of fluids from connective tissue spaces. The Journal of

[9] Krogh A, Landis EM, Turner AH. The movement of fluid through the human capillary wall in relation to venous pressure and to the colloid osmotic pressure of the blood. The

[10] Weinbaum S, Tarbell JM, Damiano ER. The structure and function of the endothelial glycocalyx layer. Annual Review of Biomedical Engineering. 2007;**9**:121-167. DOI: 10.1146/

Analgesia. 2007;**104**(4):893-897. DOI: 10.1213/01.ane.0000258015.87381.61

bolic Care. 2005;**8**:197-203. DOI: 10.1097/00075197-200503000-00015

Physiology. 1896;**19**:312-326. DOI: 10.1113/jphysiol.1896.sp000596

Journal of Clinical Investigation. 1932;**11**:63-95. DOI: 10.1172/JCI100408

A common quantitative definition of fluid overload in the literature is a percentage fluid accumulation of >10%, determined by dividing the cumulative fluid balance in liter by the patient's baseline body weight and multiplying by 100% [86, 87]. This is, however, on the assumption that the patient is volume depleted on admission to the acute unit, which is not necessarily the case as some patients have already been accumulating fluid by then. The negative effects of the excess fluid have been shown in various organ systems. In a large RCT, higher cumulative fluid balance was associated with longer mechanical ventilation duration and length of ICU stay and without reducing the incidence of shock and the need for renal replacement therapy [88]. In managing intra-abdominal hypertension and abdominal compartment syndrome, poorer outcomes have been attributed to fluid overload [89, 90], a phenomenon linked to capillary leak and tissue edema. While fluid is often aggressively given to prevent AKI, the association between fluid overload and poorer renal outcomes has been evident [86, 91, 92], prompting questions on the cause-effect relationship between fluid overload and AKI [93].

A comprehensive fluid strategy will require a close monitoring of the fluid balance. In this context, a mindset of fluids as drugs will promote careful considerations of the indications and the doses of the fluids, recognizing that more is not always better.
