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ABC of Intravenous Fluids, Electrolyte Disorders and AKI Management in Adults

INTRAVENOUS FLUIDTHERAPY IN ADULTS

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Intravenous Fluids and Electrolyte (IVF) administration is an important, common therapeutic intervention; water constitutes 60% of total body weight in men and 55% in women[1]. It is crucial to prescribe the correct fl uid type, volume, and administration rate[1]. Adequate IVF prescribing necessitates a meticulous assessment of fl uid balance and a proper understanding of the physiology and pathophysiology of the distribution of water and electrolytes in addition to the properties of common IVF[1, 2].

Intravenous fl uids should be administered only if a patient’s requirements cannot be fulfi lled through the oral or enteral route; they should be stopped as soon as possible[1]. Intravenous fl uids should be administered under stringent monitoring of the patient’s response through frequent recording of vital signs, at least daily fl uid balance charts/weight, and measurement of renal function; appropriate actions should be taken when necessary[1, 2].

Prescription of intravenous fl uid is usually carried by the most junior doctors[1, 3]. Uninitiated prescribing is a result of insuffi cient knowledge and training and could induce serious complications. Excessive or inappropriate fl uids may precipitate pulmonary oedema or severe hyponatraemia, whereas under-resuscitation can result in Acute Kidney Injury (AKI)[2, 4].

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ABC of Intravenous Fluids4

Normal distribution of water in the body: a man of 70kg total body weight:

Total Body Water (TBW) volume542L, 60% body weight (Mainly in muscles, less in fat)

ICF volume528L,40% body weight (2/3 TBW)

ECF volume514L,20% body weight (1/3 TBW)

Interstitial fl uidvolume511L,

80% of ECF

Plasmavolume53L,

20% ECF

Abbreviations: ICF5Intracellular Fluid; ECF5Extracellular Fluid

Daily fl uid balance under normal conditions: a man of 70 kg total body weight:

Input Output

Source Volume (ml) Site of loss Volume (ml)

Water 1000 Urine 1000

Food 650 Skin (insensible) 500

Oxidation (insensible) 350 Lungs (insensible) 400

Faeces 100

Total 2000 Total 2000

Adapted from[5]. Daily (24 hour) fl uid requirements of a healthy adult are 25–35ml/kg.

Daily electrolytes requirements:

Daily requirements (mmol/kg) For 70kg Adult

Sodium 1 –2 70 –140

Potassium 0.5 –1 35 –70

Calcium 0.2 –0.3 1.4 –2.1

Magnesium 0.35 –0.45 24.5 –31.5

Chloride Equal to Na Equal to Na

Bicarbonate/Acetate Use with Cl- to balance cations

and help PHUse with Cl to balance cations and help PH

Daily glucose requirements are 50–1Y00g


Intravenous Fluid Therapy in Adults5

Fluid balance in disease and injury

It is worth remembering that the physiological diffi culty in excreting an excess sodium and water load becomes more pronounced in disease and injury. This is driven by the non-specifi c metabolic responses to stress and infl ammation[5, 6]:

1. The stress response to injury or surgery stimulates secretion of ADH, catecholamines and activates Rennin-Angiotensin-Aldosterone System (RAAS). It results in Water and Salt Retention (anti-diuresis and oliguria), even in the presence of volume overload.

2. Increased systemic capillary permeability causes extravasation of albumin and fl uid into the interstitial space. It results in intravascular hypovolaemia, inducing further sodium and water retention by activation of the RAAS and secretion of ADH.

The multiple haemodynamic and non-haemodynamic stimuli for ADH secretion place acutely ill in-patients at risk of developing hyponatraemia[2, 7], and the simultaneous activation of the RAAS is probably protective.

3. RAAS activity and cellular loss of potassium secondary to protein catabolism causes potassium depletion that reduces the ability to excrete a sodium load[5, 6].

In addition[5, 6]:

4. Saline infusion causes Cl/Na overload. Hyperchloraemia induces renal vasoconstriction and the reduced GFR compromises the ability of the kidney to excrete sodium and water, see resuscitation below;

5. External pressure kidney (Abdominal Compartment Syndrome) plus increased intra-capsular pressure due to oedematous renal tissue can precipitate AKI.

NB. It is crucial, post-surgery, to diff erentiate the harmless oliguria caused by the stress response from that caused by AKI.

Further, normal fl uid and electrolyte balance can also be signifi cantly altered in malnutrition, medical treatment (e.g., Diuretics, NSAIDs), and organ dysfunction (e.g., Oedema in Heart Failure, Renal Failure, Liver Failure i.e. re-distribution)[5, 6].



Na/Cl K Other Osmolarity PH/ MWT (kDa)

Max dose (ml/Kg/24h)

Duration of ECV

expansion, hour

Indication

NSa 154/154 0 0 308 (isotonic)

5 –5.5/0 None 1–4 Res (Fluid of choice)

Hartmann’sa (HM) (~ RL)

131/111 5 Lactate (HCO3)/Ca:

29/2

279 6.5/0 None 1–4 Res Rep (Fluid of choice)

D5Wa 0/0 0 50g D/1L 280 (hypotonic)

4.5/0 Avoid over

usage

NA RM–use D/S

Gelatinb 4% (Gelofusine)

154/120 0 Succinylated,Cross-linked

274 7.4/30 None 3 –4 Consider for Res

5% Albumenb 130–160/ 130–160

0 Protein 12.5g 310 7.4/69 None 12 –24 Consider for Res

a5Crystalloid;b5Colloid

Abbreviations: MWT5Molecular Weight, kDa5Kilodalton, NS50.9% Normal Saline, Res5Resuscitation,HM5Hartmenn’s, RL5Ringer’s Lactate, Rep5Replacement, D5%W55% Dextrose in Water, RM5Routine Maintenance, D/S5Dextrose/Saline*D5%W infusion: has no eff ect on tonicity; dextrose is rapidly taken up by the cells and metabolised[2]. Thus, the steady state eff ect is that of adding water, which dilutes plasma. An isotonic solution is that with a sodium concentration [Na] approximately equal to serum [Na][2].

IV Fluid, Crystalloids and Colloids: constituents, properties and indications:

The Colloid Osmotic Pressure, [Oncotic Pressure], (mmHg) for: Plasma is 25; Gelofusin is 26 –29; 5% Albumen is 20; and 0 for Crystalloids.

Colloids vs Crystalloids for fl uid resuscitation:

Crystalloids ColloidsMWT/IV persistence Low/short High/(retained IV)Replacement volume required Large Less (increase BP more rapidly)Interstitial oedema 111 1

Cost Low HighIV5Intravenous, Y5Yes, N5No

Despite their theoretical superiority over crystalloids, colloids’ eff ect is less than expected due to capillary leak in acute illness[5]. Gelatins have a low MWT as higher MWT solutions tend to gel[8], and is rapidly excreted through the kidneys; hence short-term volume expansion. Moreover, the substantially higher cost of colloids, their adverse side eff ects’ profi le and the lack of clinical superiority over crystalloids deter their use in resuscitation[8–11].



ASSESSMENT OF VOLUME STATUS

Assess and manage patients’ fl uid and electrolyte needs as part of at least every day ward review. Extra-vascular volume defi cits do not become clinically apparent until they reach 10% of body weight.

The pre- (rarely available) and post-fl uid loss body weight is the most accurate parameter for assessing total fl uid defi cit. There is no formula available for an accurate estimation of total fl uid defi cit[12]. Hence, assessing hypovolaemia and IVF requirement is a summation of:

a. History: fl uid losses, e.g. diarrhoea and vomiting; co-morbidities; current medications etc.;

b. Clinical examination: current status and trends in:

Clinical indicators of moderate/severe volume depletion:

ECF volume: Moderate defi cit Severe defi cit

General Decreased skin turgor Atonic musclesSunken eyesNational Early Warning Score (NEWS)$5[1,13,14]

CVS Postural hypotensionTachycardia (HR.90 bpm)Collapsed veins

Hypotension (SBP,90)Absent peripheral pulses

CNS/autonomic responses Fatigue/lethargy(the commonest symptoms)

Cold extremities/Pallor Stupor/comaRR.20/minute[1].

GIT Anorexia Nausea and VomitingAnorexiaIleus

Fluid balance charts UOP,30 ml/h suggest the need for IVF

c. Laboratory investigations – current status and trends:

Serum biochemistry Disproportionately high serum urea compared to creatinine High serum lactate indicates tissue hypoperfusion High Hct/Albumen (if not caused by bleeding) Hypokalaemia indicates the need for potassium supplementation

Urine biochemistry u[Na] refl ects renal perfusion, and a low value ( ,20 mmol/L) indicates renal hypoperfusion.



Proper assessment is a collective integration of history, physical signs and laboratory fi ndings – FBC and UEs[1], followed by clinical monitoring of current status and the pattern of change in NEWS, fl uid balance charts, and weight[1]. The use of the conventional CVP/PWP and sophisticated haemodynamic parameters has limitations.

If the assessment indicates the need for parenteral fl uid:Remember the fi ve R's on prescribing intravenous fl uids:

The 5 Rs. Indication Fluid of choice Volume

1. Resuscitation#(to restore theintravascular volume and tissue perfusion)

Severe intravascular depletion

Isotonic crystalloids:NS orHM[1, 2, 8, 15]

A bolus of 500ml over ,15 minutes

Re-assess: give up to 2L of NS as rapidly as possible–Senior advice if no response

2. Routine maintenance (RM)*(to maintain the ECV and normalelectrolyte balance)

Euvolaemic but, unable to take PO or enterally (e.g. NPO pre/post-op-erative; on ventilator)(switch to PO or enteral asap)

(5% D‡10.45% saline120 KCl) – monitor for HoN/ HrN[12]

~2L or Previous 24hr UOP1

insensible losses

3. Replacement 1Ongoing losses: D/V; post-AKI polyurea,/excessive sweating, high OP stoma, etc.

HM[1] Adjust the IV RM: (“increase”) to ac-

count for the losses Correct electrolyte

defi cits (or excesses)

4. Re-distribution Abnormal fl uid distribu-tion from the circulation to the tissues:e.g. Gross oedema

“Decrease”[1] Adjust the IV RM:(“decrease”) to account for the 3rd spacing

Correct electrolyte defi cits (or excesses)

5. Re-assess and continuously monitor the clinical fl uid status/response to therapy (at least daily): a. History – fl uid losses, co-morbidities, current medications etc. b. Clinical examination – ABCDE (trends and context): BP/PR: the most important parameters to guide the volume of fl uid replacement required; Body weight (base line and daily): the best measure for assessing and monitoring volume balance–

defi cit/gain; Fluid balance charts.c. Laboratory investigations: Laboratory values (UEs); u[Na] may be helpful in patients with high volume GI losses: Reduced u[Na] excretion (,30 mmol/L)5total body Na depletion u[Na]: if,155persistent volume depletion and the need for more fl uids

NB. u[Na] values may be misleading in the presence of renal impairment or diuretic therapy

Adapted from[1].Abbreviations: NS5Normal Saline, HM5Hartmann’s Solution



Resuscitation#: balanced crystalloids, such as Hartmann’s or Ringers lactate/ acetate, are favoured over normal saline as the fi rst choice[6, 8] because comparative human studies revealed that normal saline is associated with higher s[Cl] and metabolic acidosis[16–18] as well as reduced renal blood fl ow[19]. In animal models, hyperchloraemia was long known to produce renal vasoconstriction and reduced glomerular fi ltration rate[20]. The data in relation to the eff ect on serum potassium is confl icting. Compared to balanced crystalloids, normal saline was associated with a comparable incidence of hyperkalaemia[21] in the most recent publication; higher serum potassium[22], and hyperkalaemia[23] in peri-renal transplant patients. However, this ‘physiological̕ superiority of balanced crystaloids is not yet borne out in the available limited, small, ‘clinical’ trials. A Cochrane systematic review revealed that the choice of non-buff ered salt-based (e.g. normal saline) or buff ered (modifi ed with adding bicarbonate or bicarbonate precursors – balanced crystaloids) intravenous fl uids in the peri-operative period has no infl uence on mortality, renal function and blood loss; both are safe and eff ective[24]. The use of a buff ered crystalloid compared with normal saline, in intensive care units (mostly post-operative), did not reduce the rate of AKI or renal replacement therapy[25]. Studies in kidney transplant patients revealed no diff erence in the transplant outcome between patients receiving peri-transplant normal saline or those receiving balanced solutions[18, 21–23]. There was a tendency towards increased thrombotic propensity in the balanced solutions arm; two patients lost their graft to transplant renal artery thrombosis[22].

Resuscitation: normal saline is preferred in patients with hyponatrae-mia, alkalosis, cerebrovascular disease or brain injury[26].

Routine Maintenance*: the National Institute for Health and Care Excellence (NICE) recommendation for starting routine maintenance fl uids, by giving 25–35ml/day of hypotonic crystaloids ([4% D/1/5 NS/27 mmol KCl]/L) under close monitoring to provide 1mmol/kg of Na, Cl and K[1], has since been disapproved in a recent North American publication[2]. Isotonic Fluids are recommended as the fi rst choice, because hypotonic (Na,130) IVF was the main ‘reported’ cause of hospital-acquired hyponatraemia[2]. The ‘evidence-base’ for favouring isotonic fl uids over hypotonic fl uids was from comparative prospective studies in a diff erent population, children, the majority of whom were surgical and critical care patients rather than acute admission units or general wards[2]. Of the isotonic fl uids ‘balanced’ crystalloids are probably superior to normal saline[6, 8]. However, the disparity would confi rm that close clinical and biochemical monitoring is as important as the choice of intravenous fl uid type.



Give less volume, ~20ml/Kg/day, for elderly and those with renal and heart failure[1].

4–5% D‡5is given to prevent excess catabolism and limit starvation ketosis, 50–100g of glucose/day[1, 2]. It prevents hypoglyacaemia, but does not provide complete nutritional support[1, 2]. Involve the dietician to address nutritional needs[1].

Methods of parenteral fl uid administration: IV, SC, IO (intraosseous–a rescue technique in paediatrics mainly, safe, eff ective, reliable and relatively simple).

Fluid choice was historically guided mainly by a theoretical, physiological rationale, and pre-clinical studies[1, 8]. The sparse evidence and the controversy about the ideal IVF composition in diff erent clinical settings[1,2,5–8] necessitates conducting well-structured, large, randomised, controlled trials. Currently, in either choice; judicious administration of IVF under meticulous clinical and biochemical monitoring is mandatory, and every case ought to be managed on its own merits. International guidelines were a success in disciplines such as renal medicine, and a call for guidelines in this fi eld is pertinent.

DO NOT PRESCRIBE IVF FOR.24 HOURS

CONCLUSION

Prescribing IVF should be part of the core medical pre- and post-graduate training. Hospitals need to appoint a senior medical staff members, doctors and nurses, as intravenous fl uid management champions, and arrange for periodical tutorials and workshops on the subject. Monitor and Audit.

REFERENCES

[1] National Institute for Health and Care Excellence (NICE 2013): Intravenous fl uid therapy for adults in hospital. (Clinical Guideline 174). www.nice.org.uk/CG174.

[2] Moritz, M.L. and Ayus, J.C. Maintenance Intravenous Fluids in Acutely Ill Patients. The New England Journal of Medicine (2015), Vol. 373, pp. 1350–60. DOI: 10.1056/NEJMra1412877.

[3] Lobo, D.N., Dube, M.G. and Neal, K.R. Problems with solutions: drowning in the brine of an inadequate knowledge base. Clinical Nutrition (2001), Vol. 20, No. 2, pp. 125–130.



[4] National Confi dential Enquiry into Perioperative Deaths. Extremes of age: the 1999 report of the National Confi dential Enquiry into Perioperative Deaths (1999). www.Ncepod.org.uk/pdf/1999 /99full.pdf.

[5] Frost, P. Intravenous fl uid therapy in adult inpatients. British Medical Journal (2015), pp. 350.doi: http://dx.doi.org/10.1136/bmj.g7620

[6] Powell-Tuck, J., Gosling, P. and Lobo, D.N. (2011). British Consensus Guidelines on Intravenous Fluid Therapy for Adult Surgical Patients. http://www.bapen.org.uk/pdfs/bapen_pubs/giftasup.pdf (viewed in 05.2015).

[7] Steele, A., Gowrishankar, M. and Abrahamson, S. Postoperative hyponatremia despitenear-isotonic saline infusion: a phenomenon of desalination. Annals of Internal Medicine (1997), Vol. 126, pp. 20–5.

[8] Severs, D., Hoorn, E.J. and Rookmaaker, M.B. A Critical Appraisal of Intravenous Fluids: from the physiological basis to clinical evidence. Nephrol Dial Transplant (2014), Vol. 30, pp. 178–187. doi: 10.1093/ndt/gfu005.

[9] Gosling, P., Rittoo, D. and Manji, M., Hydroxyethylstarch as a risk factor for acute renal failure in severe sepsis. Lancet (2001), Vol. 358, p. 581.

[10] Roberts I. Colloids versus crystalloids for fl uid resuscitation in critically ill patients. The Cochrane Database of Systematic Reviews 2004. CD000567.

[11] Perel, P., Roberts, I. and Ker, K. Colloids versus crystalloids for fl uid resuscitation in critically ill patients. Cochrane Database Systematic Reviews (2013), p. 2. CD000567.

[12] Uptodate. Maintenance and replacement fl uid therapy in adults (accessed 12.12.2015)

[13] Royal College of Physicians. National Early Warning Score (NEWS): standardising the assessment of acute-illness severity in the NHS. RCP, 2012.

[14] National Institute for Health and Care Excellence (NICE): Acutely ill patients in hospital: recognition of and response to acute illness in adults in hospital.

[15] KDIGO Clinical Practice Guideline for AKI. KI Supplements (2012), Vol. 2, No. 1. http://www.kidney- international.org

[16] McFarlane, C. and Lee, A. A comparison of Plasmalyte 148 and 0.9% saline for intra-operative fl uid replacement. Anaesthesia (1994), Vol. 49, pp. 779–781.

[17] Williams, E.L., Hildebrand, K.L., McCormick, S.A. and Bedel, M.J. The eff ect of intravenous lactated Ringer’s solution versus 0.9% sodium chloride solution on serum osmolality in human volunteers. Anesthesia & Analgesia (1999), Vol. 88, pp. 999–1003

[18] Hadimioglu, N., Saadawy, I. and Saglam, T. The eff ect of diff erent crystalloid solutions onacid-base balance and early kidney function after kidney transplantation. Anesthesia & Analgesia (2008), Vol. 107, pp. 264–269.

[19] Chowdhury, A.H., Cox, E.F., Francis, S.T. and Lobo, D.N. A randomized, controlled, double-blind crossover study on the eff ects of 2-L infusions of 0.9% saline and plasma-lyte (R) 148 on renal blood fl ow velocity and renal cortical tissue perfusion in healthy volunteers. Annals of Surgery (2012), Vol. 256, pp. 18–24.

[20] Wilcox, C.S. Regulation of renal blood fl ow by plasma chloride. The Journal of Clinical Investigation (1983), Vol. 71, pp. 726–735.

[21] Potura, E., Lindner, G., Biesenbach, P., et al. An acetate-buff ered balanced crystalloid versus 0.9% saline in patients with end-stage renal disease undergoing cadaveric renal transplantation: a prospective randomized controlled trial. Anesthesia & Analgesia (2015), Vol. 120, No. 1, pp. 123–9. doi: 10.1213/ANE.0000000000000419.



[22] Khajavi, M.R., Etezadi, F. and Moharari, R.S. Eff ects of normal saline vs lactated Ringer’s during renal transplantation. Renal Failure (2008), Vol. 30, pp. 535–539.

[23] O’Malley, C.M.N., Frumento, R.J. and Hardy, M.A. A Randomized, Double-Blind Comparison of Lactated Ringer’s Solution and 0.9% NaCl During Renal Transplantation. Anesthesia & Analgesia (2005), Vol. 100, No. 5, pp. 1518–1524. doi: 10.1213/01.ANE.0000150939.28904.81

[24] Burdett, E., Dushianthan, A. and Guerrero E. Perioperative buff ered versus non-buff ered fl uid administration for surgery in adults. Cochrane Database of Systematic Reviews (2012), p. 12. CD004089.

[25] Young, P., Bailey, M. and Beasley, R. Eff ect of buff ered crystalloid solution vs saline on acute kidney injury among patients in the intensive care unit: the SPLIT randomized clinical trial.The Journal of the American Medical Association (JAMA), (2015), Vol. 314, No. 16, pp. 1701–10. doi: 10.1001/jama.2015.12334.

[26] Lobo, D.N. and Awad, S. Should chloride-rich crystalloids remain the mainstay of fl uid resuscitation to prevent ‘Pre-Renal’ acute kidney injury? Kidney International (2014), Vol. 86,No. 6, pp. 1096–1105. doi: 10.1038/ki.2014.105.


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