One-liner…
Understanding how to manage maintenance fluids in critically unwell children best is a basic but important way to improve outcomes.
Background
Prescribing maintenance fluids can seem like a straightforward tick-off from the to-do list for many of us. However, considering human mass is composed of 60% water (70% for term neonates), we must get this right. This water is held in either the intracellular compartment (i.e. bound within the phospholipid membrane of cells) or in the extracellular compartment (i.e. everywhere outside the cells). The extracellular fluid can be intravascular (in the blood vessels), interstitial (around the cells) or as a component of physiological fluid such as CSF.
Some terminology
Osmolarity = the concentration of osmotically active particles dissolved in a given volume of solution, e.g. 1 mole of NaCl provides two osmoles, one each from the Na and Cl ions.
Osmolality = the concentration of osmotically active particles dissolved in a given mass of solution. This essentially equals osmolarity in humans as the solvent is water, whereby 1L ≈ 1kg.
Tonicity = the net effect of the difference in osmolality between two solutions separated by a semi-permeable membrane, i.e. how do the non-permeable components change how water will move via osmosis?
But how is this relevant to my prescribing? We need to think about the tonicity of the fluid we are giving as we don’t want to cause large shifts of fluid into and out of cells. Na+ and Cl– ions do not freely cross the cell membrane and therefore affect tonicity. Glucose, on the other hand, is very rapidly taken up by cells, and so its tonicity is only relevant at the moment of infusion. Understanding where the water in the body is and how it moves is crucial to knowing how we can artificially replicate the most balanced state during illness.
What do we need to give?
Currently, the administration of water for the paediatric population is based on the Holliday-Segar formula (100ml/kg/day for the first 10kg of weight, 50ml/kg/day for the second 10kg of weight and 20ml/kg/day for weight over 20kg). Generally, this is up to a maximum of 2.5L/day for males and 2L/day for females. It is important to know that the Holliday-Segar formula is based on limited evidence, with critics arguing that it tends to overestimate water requirements.
We need to ensure that we are giving the daily required water intake to replenish losses from both the intracellular and extracellular compartments, provide sufficient calories to prevent hypoglycaemia and maintain electrolytes within the normal range.
Humans typically require 1-2mmol/kg/day of sodium and 1mmol/kg/day of potassium (often more in neonates). In a PICU setting, sodium can come from various sources (resuscitation fluids, IV drugs and infusions, enteral feed), not just the maintenance fluids we prescribe. Most drugs are chosen to be dissolved in 0.9% sodium chloride. However, only a few need to be (e.g. co-amoxiclav, aciclovir, somatostatin and phenytoin).
The table below gives the content of some commonly used maintenance fluids. Have a look to see how their osmolarity and tonicity across the cell membrane compare to plasma.
What loss mechanisms do we need to consider?
- Renal (= urine output): anti-diuretic hormone (ADH) release from the posterior pituitary is stimulated by microchanges in plasma osmolarity. The more the ADH, the more aquaporin channels are expressed, and the more water is absorbed (it makes sense, ANTI-DIURETIC). Sodium reabsorption by aldosterone also helps water to be retained. Also, remember that our critically ill patients are vulnerable to low urine output secondary to AKI.
- Other sensible losses: e.g. vomit/gastric aspirations, diarrhoea/stoma output, drain output
- Insensible losses: evaporation from mucosal surfaces (e.g. respiratory tract), stool water content, and evaporation from skin and sweat. These losses are variable, with commonly cited figures of 300-500ml/m2/day, or from 50ml/kg/day in a neonate to 10ml/kg/day for a teenager2,3. The numbers will also vary in different disease states, i.e. higher in fevers but lower in invasive ventilation with humidification.
What happens if we give too much fluid?
It is reasonable to assume that many of the unwell patients in the PICU are in a salt- and water-conserving mode. Iatrogenic hypernatraemia is one of the main risk factors for fluid overload. Returning to our ancestral environment, fresh water and salt were scarce, so our kidneys take a long time to clear sodium loads, and trigger increased thirst and water retention through the accumulation of urea. The human body also aims to conserve supplies in illness by enhancing thirst and water retention by increasing ADH in response to stress. When our bodies are overloaded with fluid, they accumulate in interstitial spaces.
It is easiest to think of the consequences of this in a systems-based format…
- Respiratory: pulmonary oedema, pleural effusion, altered pulmonary and chest wall compliance, decreased lung volumes.
- Cardiovascular: myocardial oedema, impaired contractility, diastolic dysfunction
- Hepatic: hepatic congestion, impaired synthetic function, cholestasis
- Gastrointestinal: ascites, malabsorption, ileus, bacterial translocation
- Renal: decreased renal blood flow, renal interstitial oedema, salt and water retention
Therefore, we must consider that PICU patients may require less than typical maintenance fluids. Without thorough consideration of both volume AND sodium requirements, overload can occur quickly and be hard to correct. Fluid overload has been shown to correlate with a longer duration of mechanical ventilation, increased rate of AKI, longer PICU stay and mortality.
How to get it just right
Step 1
Consider sodium load from the beginning. How much sodium are you giving in that 500ml bag of 0.9% sodium chloride? For a <10kg infant receiving fluid at 100ml/kg/day, this is 15.4mmol/kg/day (compared to daily requirements of 1-2mmol/kg/day). Although ADH helps to control short-term changes to our fluid balance, total body salt is responsible for the long-term balance. An overall reduction in total body salt will reduce total body water and fluid overload.
Step 2
Where else are volume and electrolytes coming from? Most parenteral drugs are mixed with glucose or sodium chloride – have we considered this in our calculations?
Step 3
Less is more. PICU patients are at risk of SIADH and will generally be in a water-conserving state, so we can prevent iatrogenic dilutional hyponatraemia (and possibly worsening salt and water retention) by starting at a proportion of total maintenance volume (e.g. 50-80%) then adjusting as needed. There is growing interest in giving no maintenance fluid and using the input from drug infusions and resuscitative boluses only. Remember, we can add more if needed, but taking it away is much harder.
Jasmine, a hypothetical case
Jasmine is a 5-year-old girl weighing 18kg admitted to PICU with suspected sepsis.
She had septic shock on presentation and was resuscitated with 60ml/kg of balanced crystalloid solution and escalating vasoactive medications.
During the resuscitation, she was intubated to reduce oxygen consumption (from work of breathing), to provide left ventricular afterload reduction and facilitate line insertion. A urinary catheter was also inserted.
She has been commenced on broad-spectrum IV antibiotics. You have been asked by your consultant to prescribe IV maintenance fluids.
You retrieve the below relevant information…
- Vital signs: T 40, HR 140, BP 75/40 (52)
- Examination: mucous membranes slightly dry, skin turgor normal, mild dependent pitting oedema
- Bloods: Na 146, K 5.2, Ur 10.3, Cr 112
- Inputs (all IV and reconstituted in NaCl 0.9%): adrenaline 0.2mcg/kg/min (2ml/h), noradrenaline 0.2mcg/kg/min (2ml/h), morphine 30mcg/kg/h (1.5ml/h), midazolam 80mcg/kg/h (0.8ml/h), vecuronium 100mcg/kg/hr (1.8ml/h); hydrocortisone 1mg/kg 6hrly (1.4ml/day), cefotaxime 50mg/kg 6hrly (18ml/day), clindamycin 5mg/kg 6hrly (60ml/day), omeprazole 500mcg/kg 24hrly (22.5ml/day); total ≈ 300ml/day
- Outputs: urine output = 0.3ml/kg/hr = 130ml/day
You start with the standard approach in your unit and prescribe maintenance fluids of PlasmaLyte 148 + glucose 5% with a target total fluid input of 2/3rds maintenance (≈ 940ml/day). However, you estimate Jasmine’s insensible losses at 400ml/m2/day (~300ml/day) and realise this would give a fluid balance of +510ml/day (+28ml/kg/day), assuming her urine output does not change significantly. You also realise you would be giving ~7.5mmol/kg/day of sodium and that this excess sodium will promote further fluid retention. Is it any wonder all of our PICU patients suffer from fluid overload?!
In a discussion with your consultant, you note that Jasmine’s AKI complicates the situation. This is likely a combination of pre-renal and renal. As well as requesting relevant investigations and reviewing her drugs, you send paired urine and serum electrolytes to calculate a fractional excretion of sodium to categorise the cause as pre-renal vs other (see https://www.mdcalc.com/calc/60/fractional-excretion-sodium-fena for more information).
You agree with your consultant that, given the developing AKI, the optimal fluid strategy will be to replace urine output + insensible losses (~300ml/day). Her fluid input from drug infusions was also 300ml/day. To keep her fluid balance neutral, the nursing staff will run her maintenance fluid (PlasmaLyte 148 + glucose 5%) at a rate equal to her urine output. If the fractional excretion of sodium is <1%, you agree with your consultant that you will also ask the nurses to account for the replacement of 5% dehydration (900ml) over 48h (≈ 19ml/h). Given the present urine output of 0.3ml/kg/hr and no dehydration replacement, you estimate she will receive ~1mmol/kg/day of sodium. You, therefore, ask the nursing staff to reconstitute her IV drugs in glucose 5% wherever possible. You agree with your consultant that her electrolytes will require 6-hourly monitoring initially (particularly given the risk of SIADH and hyponatraemia) and that her fluid replacement strategy should be reviewed at least daily.
The Evidence
Studies have shown that in critical illness, the capillary leak of substances such as albumin is 3x higher than in health. This results in water- and salt leak out of the intravascular space leading to hypovolaemia. Often, clinicians aim to combat this with more fluids, of which only 20-25% is held in the intravascular compartment. This leads to progressive overload as the kidneys cannot filter the interstitial fluid that is building up. This fluid overload has been associated with longer durations of mechanical ventilation, increased rate of AKI, longer PICU stay and mortality, as mentioned earlier. The evidence also eludes to a problem known as ‘fluid creep’ – the total administration of fluid and electrolytes often vastly exceeds the amount intended due to a combination of resuscitation fluid, maintenance fluid, IV infusions, other electrolyte corrections and drug administration. The REVERSE-AKI feasibility trial suggests that fluid restriction can improve outcomes without significant renal consequences.
As well as considering volume, hyponatraemia is a harmful consequence of incorrect administration of fluids. Many years ago, there was a large body of evidence in reports from Northern Irish hospitals showing children who received large volumes of hypotonic IV fluids subsequently developed hyponatraemic encephalopathy and cerebral oedema. A 2015 study published in the Lancet demonstrated a reduction in hyponatraemia by adopting an isotonic strategy compared with a hypotonic strategy. A fluid shift, if you will.
Putting all this together, we risk hypernatremia if we adopt a fluid-restrictive strategy with isotonic fluids. In addition, unbalanced isotonic fluids such as 0.9% sodium chloride can provide an excess of chloride, leading to metabolic acidosis, renal vasoconstriction and renal hypoperfusion. An alternative option is to give much lower volumes of balanced hypotonic fluids. However, it is widely considered that this would only be safe in a closely monitored environment like PICU with regular electrolyte measurements. Current practice is still isotonic fluids with a slight volume restriction, but there may/may not be another fluid shift coming…
References
Alobaidi R, Basu RK, Decaen A, et al. Fluid Accumulation in Critically Ill Children. Crit Care Med. 2020;48:1034-1041. doi:10.1097/CCM.0000000000004376
Fluids and Electrolytes, British National Formulary for Children. NICE . Available at: https://bnfc.nice.org.uk/treatment-summaries/fluids-and-electrolytes/ (Accessed: April 3, 2023).
Holliday MA, SegarWE. The maintenance need for water in parenteral fluid therapy. Pediatrics. 1957 May;19(5):823-32. PMID: 13431307
J. P. Nicholson, M. R. Wolmarans, G. R. Park, The role of albumin in critical illness, BJA: British Journal of Anaesthesia, Volume 85, Issue 4, 1 October 2000, Pages 599–610, https://doi.org/10.1093/bja/85.4.599
Malbrain MLNG, Regenmortel N Van, Saugel B, et al. Principles of fluid management and stewardship in septic shock: it is time to consider the four D’s and the four phases of fluid therapy. Ann Intensive Care. 2018;8:66. doi:10.1186/s13613-018-0402-x
McNab S, Duke T, South M, et al. 140 mmol/L of sodium versus 77 mmol/L of sodium in maintenance intravenous fluid therapy for children in hospital (PIMS): a randomised controlled double-blind trial. Lancet (London, England). 2015;385(9974):1190-1197. doi:10.1016/S0140-6736(14)61459-8
Overview: Intravenous fluid therapy in children and Young People In Hospital: Guidance (2015) NICE. Available at: https://www.nice.org.uk/guidance/ng29 (Accessed: April 3, 2023).
Regenmortel N Van, Verbrugghe W, Roelant E, et al. Maintenance fluid therapy and fluid creep impose more significant fluid, sodium, and chloride burdens than resuscitation fluids in critically ill patients: a retrospective study in a tertiary mixed ICU population. Intensive Care Med. 2018;44(4):409-417. doi:10.1007/s00134-018-5147-3
Rein JL, Coca SG. “I don’t get no respect”: The role of chloride in acute kidney injury. Am J Physiol – Ren Physiol. 2019;316(3):F587-F605. doi:10.1152/ajprenal.00130.2018
Vaara ST, Ostermann M, Bitker L, et al. Restrictive fluid management versus usual care in acute kidney injury (REVERSE-AKI): a pilot randomized controlled feasibility trial. Intensive Care Med. 2021;47(6):665-673. doi:10.1007/s00134-021-06401-6
Van Regenmortel N, Verbrugghe W, Roelant E, Van den Wyngaert T, Jorens PG. Maintenance fluid therapy and fluid creep impose more significant fluid, sodium, and chloride burdens than resuscitation fluids in critically ill patients: a retrospective study in a tertiary mixed ICU population. Intensive Care Med. 2018 Apr;44(4):409-417. doi: 10.1007/s00134-018-5147-3. Epub 2018 Mar 27. PMID: 29589054; PMCID: PMC5924672.
About PICSTAR
PICSTAR is a trainee-led research network open to all doctors, nurses and allied health trainees within Paediatric Intensive Care. We are the trainee arm of the Paediatric Critical Care Society – Study Group (PCCS-SG) and work with them on research, audit and service evaluation.
If you would like to join PICSTAR and get involved in projects, have ideas you would like to propose or get advice/mentorship via PCCS-SG, don’t hesitate to contact us at picstar.network@gmail.com. See their website for more: https://pccsociety.uk/research/picstar/
