Guideline 4.1 Fluid assessment and management in adults

We recommend assessment of fluid status when prompted by clinical circumstances, and on a quarterly basis for stable patients. [1C]

We suggest a multidisciplinary approach to fluid assessment, with patient involvement and the adoption of patient friendly terminology such as “target weight”, “fluid gain” and “over hydration”. [2D]

We suggest supplementing clinical assessment of fluid status with a validated objective measurement, such as bioimpedance, at regular intervals, when clinical assessment is unclear, and following an intercurrent illness. [2C]

We recommend a dialysate temperature not greater than 36’C if standardised. [1C]

We recommend avoiding excessive ultrafiltration rates by addressing fluid gains, accepting staged achievement of target weight, or using an augmented schedule, as necessary. [1B]

We recommend prompt nursing intervention to restore haemodynamic stability in symptomatic / severe intradialytic hypotension, with such interventions leading to clinical review. [1C]

Rationale

Fluid control is an essential clinical goal of maintenance haemodialysis, but correct fluid management requires clinicians to steer between the two competing / overlapping problems of fluid overload and intra dialytic hypotension.

Failure to control fluid overload may lead to obvious short term effects including hypertension and breathlessness, and nephrology trainees quickly become familiar with the emergency dialysis admission with pulmonary oedema. In the longer term also, chronic fluid overload is one of the main drivers of hypertension and is independently associated with poor outcomes: for example, in a US study of over 10,000 prevalent haemodialysis patients, Flythe reported clinical outcomes over 2 years’ follow up, according to achievement of target weight during the baseline month [1]. Compared to those achieving within 2kg of target weight on at least 70% of sessions, the 15% of patients frequently remaining over hydrated post dialysis had increased mortality (HR 1.28, 95%CI 1.15 1.43) as did the 7% of patients who were frequently under hydrated post dialysis (HR 1.22, 95%CI 1.05 1.40).

Often competing, though sometimes associated with fluid control, is intra dialytic hypotension, which also has immediate consequences familiar in the dialysis unit, including dizziness and cramps, as well as more long term adverse effects. For example, Sands studied the occurrence of intra dialytic hypotension (defined as a drop in systolic blood pressure of at least 30mmHg, to below 90mmHg) in 1137 patients in 13 dialysis facilities, over an average period of 3 months [2]. With this definition, hypotension complicated 17.2% of sessions, affecting 74.9% of patients at least once, and 16.2% of patients on at least one third of their sessions. Those most prone to intra dialytic hypotension were older, more comorbid and with lower pre dialysis blood pressure, with associated sessional factors including high ultrafiltration volume and non achievement of target weight. Outcomes associated with intra dialytic hypotension included shortened survival and increased hospital admission.

The two main treatment parameters by which clinicians aim to optimize fluid control are target weight and ultrafiltration rate.

Since the earliest days of dialysis, setting ultrafiltration to achieve a set target weight post dialysis, at which the patient is at their correct volume (or “dry”), has been the accepted method of maintaining a consistent volume state, but the method is dependent on accurate estimation of the correct target weight. Though most often assessed by clinical examination, the inaccuracy of this method is widely appreciated so that both overestimation and underestimation are common, with the former contributing to hypertension and left ventricular hypertrophy, and the latter accelerating the loss of residual kidney function and perhaps risking myocardial stunning.

To improve on clinical assessment, nephrologists at one time advocated “probing” target weight: gradual reduction until patients report symptoms suggesting hypovolaemia, but this may reduce treatment compliance and a more collaborative approach is more common. Where possible, patients should be asked to participate in monitoring their fluid status. To this end, terminology should be simple and intuitively understood: for example, when discussing target weight, the term “dry weight” can give the impression that the aim is to remove as much fluid as possible, and “ideal weight” can be confusing as it is also used to describe the preferred body mass index. Although less accurate, “hydration” is a more familiar term than “volume” as a description of fluid status. Stable patients should be assessed for target weight changes perhaps quarterly, but staff and patients should be particularly vigilant when changes in flesh weight are likely, such as following hospital admission, or when starting nutritional supplementation. Fluid management often requires input from a multidisciplinary team, so a documented policy may ensure that the approach is consistent.

Improvement on clinical assessment using objective methods for selecting target weight has been sought for a long time, though no single measurement has so far gained widespread acceptance. Methods have fallen into one of a number of categories: imaging (such as inferior vena cava diameter), biochemistry (such as brain natriuretic peptide), electrophysiology (such as bioimpedance) and dynamic intradialytic measurement (such as blood volume monitoring). Many publications address one or more of these methods, and several detailed reviews are available.

Some of these studies suffer from the limitations of self referencing design (demonstrating that the use of method X to guide selection of target weight, reduces the frequency of over hydration as defined by method X) and improvement in clinical outcomes are often harder to demonstrate. For example, Leung studied intradialytic hypotension in 32 haemodialysis patients during 8 weeks of standard care and 8 weeks during which ultrafiltration was informed by blood volume monitoring, but no advantage was seen in terms of hypotension frequency or symptoms [3].

No clear recommendation can be made regarding the optimal method, but when clinical assessment feels uncertain, it seems very reasonable to supplement this with an objective measure, and bioimpedance has some of the most promising data on clinically relevant endpoints. In a randomized study of 156 patients, Hur used bioimpedance data to adjust target weight in the intervention group, whilst control patients had bioimpedance measured but not available to treating physicians [4]. Over the 12 month study, bioimpedance defined fluid overload was reduced in the intervention group, as was blood pressure and left ventricular mass index (131±36 to 116±29g/m², p<0.001).

Regardless of the final volume achieved, the rate of ultrafiltration appears separately to influence intra dialytic hypotension and clinical outcome. In a DOPPS study of 22,000 patients in 7 countries, Saran observed that an ultrafiltration rate over 10ml/h/kg was associated with both intra dialytic hypotension (RR 1.30, p=0.04) and mortality (RR 1.09, p=0.02) [5]. And using data from the HEMO study (N = 1846), Flythe divided patients according to ultrafiltration rate into three groups: less than 10, 10 13, and over 13ml/h/kg, demonstrating increased mortality in the highest ultrafiltration rate group (HR 1.59, 95%CI 1.29 1.96) [6]. When treating ultrafiltration rate as a continuous variable (using a cubic spline method) the authors identified 10ml/h/kg as the threshold beyond which mortality begins to increase, possibly quite sharply.

These studies are non interventional, therefore associations are with observed (rather than prescribed) ultrafiltration rate, and there is also a close interaction with session length (since rate is obviously the volume over the time) but these data provide a convincing argument for avoidance of excessive rates. This should not however be at the expense of non achievement of target weight and acceptance of over hydration (though staged achievement over a number of sessions is frequently appropriate) but rather should focus clinicians on session length or addressing fluid gains between dialysis sessions. The ultrafiltration required during dialysis depends on the degree of over hydration present at the start of the session, so restricting fluid intake reduces ultrafiltration rate, and is part of standard advice for the majority of patients. Consideration must be given to the cause of increased fluid intake such as habitual drinking or thirst associated with either dietary sodium intake or raised blood glucose. Advice on managing fluid intake is therefore best delivered on an individualised basis, as part of a dietary management plan to support adherence and patient experience. This topic is covered in guidelines for the nutritional management of kidney disease.

Other relevant aspects of the dialysis prescription include dialysate sodium and temperature.

Sodium balance, thirst and fluid control are also influenced by dialysate sodium. Many observational studies report lower fluid gains and lower blood pressure in patients treated with low dialysate Na (typically 136 138mmol/l). Antihypertensive treatment is frequently overlooked in large studies, but reasonable supportive evidence can also be found in interventional studies. For example, Gumrukcuoglu reduced dialysate sodium from 140 to 137mmol/l in 41 patients over 6 months, reporting reduced fluid gains, and no blood pressure change but a reduction in antihypertensive use from 1.9 to 1.2 agents per patient [7]. This potential benefit was not without drawbacks however: in common with other groups, investigators also found that cramps and intra dialytic hypotension became more frequent.

Lowering dialysate sodium therefore does appear to improve fluid control and blood pressure, albeit with some side effects, however another note of caution arises from observations on mortality in different dialysate sodium groups. Studying almost 30,000 patients from DOPPS phases 1 4, with dialysate sodium varying between 138 and 142mmol/l in 90% of patients, Hecking found that higher dialysate sodium was, as expected, associated with modestly increased fluid gain and systolic blood pressure (increasing by 0.17% body weight and 0.66mmHg per 2mmol/l increase in dialysate sodium) [8]. However, when addressing indication bias by studying only the 56% of facilities using a standardised dialysate sodium, they found that higher dialysate sodium was unexpectedly associated with reduced mortality (HR 0.88 per 2mmol/l increase in dialysate sodium, 95%CI 0.83 0.94). There is insufficient consistency in the literature for a clear recommendation on dialysate sodium, though if a standardised dialysate sodium is used for all patients, some clinicians would avoid a choice below 140mmol/l.

Dialysate temperature has been consistently associated with intra dialytic hypotension. Even thermoneutral haemodialysis (temperature matched so that the dialysis circuit neither heats nor cools the patient) leads to an increase in core temperature, though it is not clear if this is due to reduced heat loss (for example due to cutaneous vasoconstriction) or increased thermogenesis (for example due to increased cardiac output) [9]. Reduced dialysate temperature has therefore been the subject of a number of interventional studies and two meta analyses [10, 11].

In the most recent of these, Mustafa reported on 26 studies totalling 484 patients [11], observing an average 70 (95%CI 49 89) percent reduction in hypotension, though with an increase in cold related symptoms. Twenty four of these studies however were either small (less than 20 patients) or of short duration (less than 3 sessions). The two largest studies provide further insight: in Maggiore’s study of 95 patients over 12 sessions [12], isothermic (in which dialysate temperature is set so that core temperature is unchanged) rather than thermoneutral dialysis reduced hypotension from 50 to 25% of sessions. In Fine’s study of 128 patients over 10 sessions [13], 35’C dialysate rather than 37’C similarly reduced hypotension, but the benefit was seen only in those with subnormal temperature before dialysis. Preventing temperature rise therefore appears to be more important than cooling, which may be achieved on an individual basis using dialysate 0.5 1.0 degree lower than core temperature or in the whole unit by using dialysate temperature 36’C or lower. The latter is probably adequate for most patients, with individualisation seeming a reasonable option for those with persisting hypotension or cold related symptoms, and it is reasonably clear that if a standardised dialysate temperature is being used, then the choice should be at or under 36’C.

Regardless of the quality of dialysis prescription, intra dialytic hypotension will still occur, in some patients more than others, for which prompt nursing intervention is essential [14]. Common measures include leg raised positioning, ceasing ultrafiltration, and fluid administration (saline being as good as albumin and far cheaper [15]). Measures for “simple” intra dialytic hypotension should be coupled with assessment for underlying intercurrent illness (such as infection or cardiac arrhythmia) or less commonly a specific dialysis complication (such as air embolism or dialyser reaction). Frequent intervention should lead to re assessment of target weight / ultrafiltration setting and a medication review in some cases predialysis hypertension may be preferable to dialysis intolerance. Specific pharmacological measures are rarely used but the alfa agonist Midodrine has reasonable supportive evidence: in meta analysis the average improvement (increase) in systolic/diastolic post dialysis blood pressure was 12.4/7.7mmHg [16].

References

1. Flythe J.E., et al., Associations of Posthaemodialysis Weights above and below Target Weight with All Cause and Cardiovascular Mortality. CJASN May 2015, 10 (5) 808 816
2. Sands JJ, Usvyat LA, Sullivan T, et al. Intradialytic hypotension: frequency, sources of variation and correlation with clinical outcome. Hemodial Int 2014; 18:415
3. Leung KCW et al, Randomized Crossover Trial of Blood Volume Monitoring Guided Ultrafiltration Biofeedback to Reduce Intradialytic Hypotensive Episodes with Haemodialysis. Clin J Am Soc Nephrol. 2017 Nov 7;12(11):1831 1840
4. Hur E., et al., Effect of Fluid Management Guided by Bioimpedance Spectroscopy on Cardiovascular Parameters in Haemodialysis Patients: A Randomized Controlled Trial. AJKD 2013, 61(6): 957 965
5. Saran R., et al, Longer treatment time and slower ultrafiltration in haemodialysis: associations with reduced mortality in the DOPPS. Kidney Int. 2006 Apr;69(7):1222 8.
6. Flythe J.E., et al., Rapid fluid removal during dialysis is associated with cardiovascular morbidity and mortality. Kidney Int. 2011; 79:250 257
7. GümrükçüoÄŸlu HA, Arı E, Akyol A, et al. Effects of lowering dialysate sodium on carotid artery atherosclerosis and endothelial dysfunction in maintenance haemodialysis patients. Int Urol Nephrol. 2012 Dec;44(6):1833 9
8. Hecking M, et al., Dialysate sodium concentration and the association with interdialytic weight gain, hospitalization, and mortality. Clin J Am Soc Nephrol. 2012 Jan;7(1):92 100
9. van der Sande FM, Rosales LM, Brener Z, et al. Effect of ultrafiltration on thermal variables, skin temperature, skin blood flow, and energy expenditure during ultrapure haemodialysis. J Am Soc Nephrol 2005; 16:1824.
10. Selby NM, McIntyre CW. A systematic review of the clinical effects of reducing dialysate fluid temperature. Nephrol Dial Transplant 2006; 21:1883
11. Mustafa RA, Bdair F, Akl EA, et al. Effect of Lowering the Dialysate Temperature in Chronic Haemodialysis: A Systematic Review and Meta Analysis. Clin J Am Soc Nephrol 2016; 11:442
12. Maggiore Q, et al., Study Group of Thermal Balance and Vascular Stability: The effects of control of thermal balance on vascular stability in haemodialysis patients: Results of the European randomized clinical trial. Am J Kidney Dis 40: 280–290, 2002
13. Fine A, Penner B: The protective effect of cool dialysate is dependent on patients’ predialysis temperature. Am J Kidney Dis 28: 262–265
14. Santos SF, Peixoto AJ, Perazella MA. How should we manage adverse intradialytic blood pressure changes? Adv Chronic Kidney Dis 2012; 19:158.
15. Knoll GA, Grabowski JA, Dervin GF, O’Rourke K. A randomized, controlled trial of albumin versus saline for the treatment of intradialytic hypotension. J Am Soc Nephrol 2004; 15:487.
16. Prakash S, Garg AX, Heidenheim AP, House AA. Midodrine appears to be safe and effective for dialysis induced hypotension: a systematic review. Nephrol Dial Transplant 2004; 19:2553.

Guideline 4.2 Paediatric fluid considerations

In growing children we recommend clinical assessment of fluid status and target weight, and dietetic assessment, at least monthly. [1C]

We suggest supplementing clinical assessment with a validated objective measure of fluid status such as bioimpedance, on a monthly basis or more frequently during periods of rapid growth or illness. [2C]

We recommend regular assessment of ultrafiltration tolerance, using extended times to avoid excessive ultrafiltration rates. [1D]

Rationale

Assessment of target weight in children and adolescents is particularly challenging as it needs frequent adjustment in line with growth or periods of illness. This is particularly true for infants and adolescents during rapid phases of growth. Overestimation of target weight will result in chronic fluid overload leading to hypertension and left ventricular hypertrophy, whereas chronic under hydration is likely to detrimentally affect residual kidney function and lead to increased symptomatic hypotension both during and immediately post dialysis. Hypotensive tendency is also multifactorial and cannot alone be relied on to ascertain a patient’s target weight. It is therefore essential that target weight is adjusted at least on a monthly basis following clinical assessment, in conjunction with dietetic review. [1,2]

References

1. Fischbach M, Zita N, Birmele B, Geisert J (1998) Sequential hypertonic dialysis (SHD) in children. Pediatr Nephrol 2(4):442–446
2. Fischbach M, Mengus L, Simeoni U, Durringer R, Mark J, De Geeter B, Hamel G, Geisert J (1991) Dialyse à double profil: ultrafiltration et sodium variables. Description et validation clinique chez l’enfant. Néphrologie 12:179–183