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What Is the Evidence Base for Fluid Resuscitation in Acute Medicine?

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What Is the Evidence Base for Fluid Resuscitation in Acute Medicine? Clinical Medicine 2018 Vol 18, No 3: 225–30 REVIEW W h a t i s t h e e v i d e n c e b a s e f o r fl u i d r e s u s c i t a t i o n i n a c u t e medicine? Authors: A d a m S e c c o m b e A, * a n d E l i z a b e t h S a p e y B, * Intravenous fl uids are commonly prescribed but uncertainty therapy’. 6 Despite this, evidence to describe the indications, dose remains about how to assess when fl uids are required and how and rate of administration of IV fluid is lacking, as is the use of IV much to give, particularly in our multimorbid, polymedicated fluid over the course of a patient’s illness. Medical practitioners and ageing population. Furthermore, studies have noted that currently rely on their clinical acumen alone to guide prescribing fl uid resuscitation can be harmful even if clinical evidence of practices, akin to the ‘science of uncertainty and art of probability’ ABSTRACT hypervolaemia is not present. Two recent guidelines have ac- described by Sir William Osler in the last century. knowledged a limited evidence base to guide fl uid assessment. Common practice is to use the clinical features of hypovolaemia A recommended means to assess hypovolaemia includes and hypervolaemia to signal when treatment should be started assessment of fl uid responsiveness. Fluid responsiveness is a and stopped. Such features are well described; 7 however, none rise in stroke volume following an increase in preload, achieved are specific to volume status 8 and many are not easy to assess. 9 using a fl uid challenge or a passive leg raise. However, the A recent systematic review of 30 studies found that clinical means of defi ning fl uid responsiveness and its ability to features (including hypotension and tachycardia) were not reliable identify patients who would benefi t from fl uid resuscitation is predictors of hypovolaemia.10 The same is true of features of currently unclear. This review discusses the current guidelines hypervolaemia, which are present in many conditions. 8 Even if about, and the evidence base for the provision of, intravenous it could be diagnosed accurately, hypervolaemia due to excess fl uids in the acutely unwell medical patient. It highlights how fluid is an iatrogenic overdose and should not be used as a little evidence is available to guide medical practice. marker to stop fluid administration. In support of this, a recent trial in Zambia randomised hypotensive, septic adults to a usual K E Y W O R D S : Fluid resuscitation , fl uid assessment , fl uid responsiveness , care group (IV fluid determined by the treating clinician) or a passive leg raise , water-electrolyte balance , fl uid therapy sepsis protocol (aggressive IV fluid limited only by clinical signs of hypervolaemia, alongside vasopressors and blood transfusion when indicated). 11 Use of the sepsis protocol led to a significant Introduction increase in in-hospital mortality (48.1%) compared to usual care (33.0%). However, a high proportion of participants had human ‘Medicine is a science of uncertainty and an art of probability.’ immunodeficiency virus (89.5%) making it unclear whether these Sir William Osler (1849–1919). results can be extrapolated to a general medical population. Intravenous (IV) fluid is one of the most commonly prescribed Of concern, harm from fluids has been demonstrated even in hospital treatments. Despite its low cost1 the annual NHS the absence of hypervolaemia. The FEAST (Fluid Expansion As spend on IV fluid is in excess of £156 million. 2 IV fluid use in Supportive Therapy) trial, a randomised controlled trial involving some resuscitation scenarios, such as traumatic blood loss, is East African children with a severe febrile illness, noted that fluid well evidenced. 3 In acute medical scenarios such as shock, the boluses (using either 0.9% saline or albumin) were associated with benefits are less well documented, although fluid therapy is highly an excess three deaths in every hundred patients, compared to 12 recommended in many guidelines and reviews, for example in conservative maintenance fluids alone. A reanalysis of this study a recent review which stated that ‘fluid therapy…is an essential suggested that cardiovascular collapse was linked to the increased part of the treatment of any form of shock’. 4 Acute kidney injury mortality rather than respiratory failure due to pulmonary 13 guidelines advise that we should identify and correct hypovolaemia oedema. Despite the lack of high-quality IV fluid trials in through ‘adequate’ fluid replacement, 5 and international sepsis developed world populations, there is a signal of harm including 14 guidelines state that the use of IV fluid ‘is a cornerstone of modern complications noted in one in five patients in the NHS. Consistent with this, observational studies performed in an intensive care setting have found associations between a positive fluid balance 15–18 Authors: A research fellow and consultant in acute medicine, Acute and increased mortality in inflammatory conditions and AKI. Medicinal Unit, University Hospital Birmingham NHS Foundation Patient variability and fluid assessment Trust, Birmingham, UK ; B reader and consultant in respiratory and general medicine, Institute of Inflammation and Ageing, University Variations in patient physiology and pathology impact upon the o f B i r m i n g h a m , B i r m i n g h a m , U K ; * b o t h a u t h o r s c o n t r i b u t e d e q u a l l y clinical assessment of fluid status, as summarised in Fig 1 . © Royal College of Physicians 2018. All rights reserved. 225 CMJv18n3-Sapey.indd 225 5/17/18 4:21 PM Adam Seccombe and Elizabeth Sapey Cardiovascular Reduced glomerular Impaired thirst adaptaons filtraon rate Physiological ageing Inflammatory Cardiac condions (eg sepsis) Renal Acute organ failure Acute illness Fluid balance Comorbidies (eg kidney injury) Endocrine Fig 1. Factors that can affect Increased fluid a fl uid assessment. Four groups losses Gastro- intesnal of factors are depicted that (eg gastroenteris) affect a patient’s fl uid balance Medicaons and therefore a fl uid assessment. These factors are further broken down into subgroups, Affecng fluid Indirect effects Affecng fluid which illustrate the potential retenon (eg (eg excreon complexities involved. corcosteroids) ancholinergics) (eg diurecs) Physiological ageing impacts organ systems and the 2015 in status, making the assessment of fluid status exceptionally Cochrane review noted there was ‘limited evidence of the challenging. diagnostic utility of any individual clinical symptom, sign or test, or combination of tests, to indicate water-loss dehydration in Recommendations from guidelines older people.’ 19 For example, maximal cardiac output declines with age, even in the absence of hypertension or cardiovascular In the last decade, two major guidelines have attempted to disease. 20 A decrease in heart rate response is seen to stressors, address the uncertainty regarding fluid assessment. which correlates with a reduced responsiveness of β-adrenoceptors The Surviving Sepsis Campaign (SSC) took a prescriptive to adrenergic stimuli, blunting the tachycardia that can identify approach to fluid use in sepsis, advising a fixed dose once septic hypovolaemia. This decline is partially compensated by an shock is identified. 6 It ‘strongly’ recommends 30 mL/kg of IV increase in the venous return, as the α-adrenoceptor-mediated fluid within 3 hours in patients who meet the criteria for septic venoconstriction is less affected by ageing. 21 shock (hypotension or lactate ≥4 mmol/L). Despite this advice, the This physiological variability is further accentuated by guideline acknowledges the evidence for their recommendation comorbidities. Chronic organ dysfunction alters fluid homeostasis. is weak, noting ‘there is little available evidence from RCTs to For example, a reduced cardiac output in heart failure causes support its [IV fluid] practice’. inappropriate activation of the renin–angiotensin system and a The recommendation is based on the results of a single-centre, consequent expansion of the extracellular fluid compartment. 22 unblinded trial involving 263 septic patients. 26 It found a 16% Medications used to manage chronic disease can also alter fluid mortality reduction when an ‘early goal-directed therapy’ balance, by direct action, eg side effects such as diarrhoea and (EGDT) protocol was used in place of usual care. However, vomiting, or through indirect means. Anticholinergic medications three subsequent trials, involving a combined total of 4,175 block parasympathetic signals to the salivary glands, causing patients, found no benefit of EGDT compared to usual care. 27–29 xerostomia. If mild, this can lead to an increased fluid intake to Furthermore, a retrospective cohort study found that 67% of moisten the mouth. Conversely, if severe, xerostomia can interfere patients had evidence of fluid overload at 24 hours when EGDT with a patient's ability to swallow and prevent adequate hydration. 23 recommendations were followed, with a corresponding 92% Fluid assessment is made yet more complex in the presence increased risk of mortality. 30 of acute illness and injury. 6 For example, sepsis affects the If initial fluid resuscitation is followed by ongoing hypotension cardiovascular system in multiple ways. Hypovolaemia occurs or hyperlactataemia, the SSC guideline recommends the use due to direct fluid loss, including insensible losses due to fever. of physiological variables to determine the need for additional Sepsis has a direct inhibitory impact on cardiac function, reducing IV fluid. 6 Recommended variables include central venous 24 contractility and limiting cardiac output. Vasodilatation causes pressure (CVP), central venous oxygen saturation (S cv O2 ), a reduction in the systemic vascular resistance and, if severe, a bedside echocardiography and a dynamic assessment of fluid fall in blood pressure.
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