Management of fluids in neonatal surgery

Learning objectives.

By reading this article, you should be able to:

• •Explain the factors that are important in determining the type and amount of fluids given to neonates during surgery.
• •Describe the indications and safeguards of blood and blood product administration in the neonate.
• •Recognise the challenges of assessing whether a neonate requires fluids or is fluid replete.

Key points.

• •Neonatal fluid homeostasis depends on the stage of cardiorespiratory adaptation and the onset of postnatal diuresis.
• •Neonates should have regular blood glucose monitoring perioperatively and normoglycaemia should be maintained.
• •Isotonic salt solutions containing glucose 1–2.5% can be given as maintenance fluids to healthy term neonates.
• •The decision to transfuse a neonate depends on the clinical context, gestational age, and premorbid status.
• •Classical monitoring can be combined with transoesophageal Doppler to guide fluid therapy.

Management of fluids in the neonate undergoing major surgery is complex, and is influenced by the gestational age, postnatal age, physiological maturation of organ systems, type of surgery, concomitant illness, and blood loss. In addition, prematurity increases these challenges, as organ systems are immature and body fluid compositions are different to that of a healthy term baby.

Much of the evidence is derived from the critically ill neonate; thus, caution must be exercised in extrapolating these data to the neonate undergoing surgery.

Neonatal physiology and cardiorespiratory adaptation at birth

Changes in body composition and cardiorespiratory adaptation

The transition from fetal life to neonatal life involves significant changes in the body water composition, and depends on the gestational age at birth and the stage of cardiorespiratory adaptation (Fig 1).¹ The proportion of extracellular fluid (ECF) is higher in preterm infants and depends on the level of prematurity.

Fig 1.

Changes in total body water (TBW) and Extracellular fluid volume (ECF) over the first three years of life.

Postnatal diuresis

Soon after birth, pulmonary vascular resistance decreases dramatically with a consequent increase in blood flow to the lungs and left atrium. This stimulates the production of atrial natriuretic peptide, which in turn stimulates sodium (Na) and water diuresis from the kidneys, and results in a decrease in the ECF volume.

This cardiorespiratory adaptation results in a physiological weight loss of 5–10% in term neonates and up to 15% in preterm neonates. Whilst weight loss in health term babies reaches its nadir at around 5 days with a return to the birth weight within 7 days, this return to the birth weight can take much longer in a preterm neonate.¹

It is routine practice to delay the administration of Na until postnatal diuresis has occurred, as neonates have a limited capacity to excrete excess Na and water. This is particularly so in premature neonates.²

Renal physiology

Neonatal kidney function is characterised by:

• (i)decreased glomerular filtration rate (GFR);
• (ii)decreased ability to concentrate urine or dilute urine;
• (iii)immature renal tubules with reduced capacity to absorb Na from the distal tubules.³

Reduced GFR

At birth, kidney function is characterised by a low GFR, because of low MAP and high intrarenal vascular resistance. The GFR then begins to increase, in response to an increased MAP and the decline in renal vascular resistance.

Concentrating ability

At birth, the renal tubules have a limited capacity to concentrate urine because of the shorter loops of Henle and reduced tonicity of the medullary interstinum.⁴ The limited ability to produce concentrated urine means neonates can become dehydrated easily.

Prematurity

The renal system of a very-low-birth-weight (VLBW) infant or premature infant is profoundly different from that of a term infant and must be taken into consideration when assessing needs for fluids. The effective renal blood flow is reported to be as low as 20 ml min⁻¹ (1.73 m)⁻² in a premature infant, compared to 45 ml min⁻¹ (1.73 m)⁻² by 35 weeks of gestation and 83 ml min⁻¹ (1.73 m)⁻² in the term infant. An increase in GFR is generally much lower in the VLBW infant and takes much longer in childhood to reach adult values. Because the GFR and renal blood flow are low, infants, particularly those who are preterm, have limited ability to handle large volumes of fluids and can easily become ‘overloaded’.³

Neuroendocrine control of fluids and electrolyte imbalance

In the first days of life, the antidiuretic hormone (ADH) concentrations are high; thus, renal water losses remain low. In neonates, hypoxaemia, acidaemia, hypercarbia, volume depletion, the need for assisted ventilation, and sepsis are all potent stimulants of persistent ADH release; therefore, fluids are often restricted after surgery.⁴

Aldosterone secretion is slow to respond to a high Na load, and therefore, it is recommended that Na be excluded from the maintenance fluid until postnatal diuresis has occurred. After that, supplementation of Na is important to avoid hyponatraemia, as the renin–angiotensin-aldosterone system has a limited capacity to retain Na, because the renal tubules are partially unresponsive to aldosterone.

Water requirements

Maintenance fluids are required for metabolism, and for replacement of ongoing sensible losses (kidneys and gastrointestinal tract) and insensible losses from the skin, viscera, and the respiratory system.² In premature neonates, these insensible losses can be much higher. Their smaller size, higher body-surface-area-to-body-weight ratio, increased thermal conductance, thinner and more permeable skin, and increased ventilatory frequency all contribute to increased insensible losses.⁵

Radiant heaters and phototherapy have also been implicated in increased transepidermal water losses, particularly in the preterm neonate.

Water loss from the respiratory tract can be minimised by using heat and moisture exchangers and the circle system.

The daily increase in maintenance fluid from birth to day 5 is different in term neonates and preterm infants, and this reflects their different physiological needs (Table 1).⁵

Table 1.

Water requirements in neonates according to postnatal age and birth weight.⁵ LBW, low birth weight (<2.5 kg); VLBW, very low birth weight (<1.5 kg); ELBW, extra low birth weight (<1 kg)

Postnatal day	Water requirements (ml kg−1 day−1)
	Term delivery or LBW	VLBW or ELBW
0–1	50–60	80–90
2	70–80	120
3	100–120	150
4	120–150	150
5	150–180	180

Perioperative fluid management

The Association of Paediatric Anaesthetists (APA) guidelines recommend that perioperative fluid management be divided into three parts:

• (i)replacement of fluid deficits;
• (ii)administration of maintenance fluids;
• (iii)replacement of any losses.⁶

Replacement of fluid deficits

In general, neonates undergoing elective surgery should be reasonably well hydrated because of the current practice of minimising fasting times. Fasting fluid deficits should also be minimised even in infants who are ‘nil by mouth’, and ideally these infants should receive i.v. fluids perioperatively.⁵

Determining the level of deficit involves a thorough assessment of the patient (including history and examination), laboratory results, point-of-care (POC) testing results, medical charts, daily weight measurement records, and fluid charts.

While there is no consensus on the volume and speed of fluid required to correct the deficit, NICE guidelines recommend that term neonates showing signs of dehydration be given isotonic glucose-free fluid 20 ml kg⁻¹ over less than 10 min.⁶

It is recommended that, where possible, preoperative fluid deficits are corrected before induction of anaesthesia.⁷

Administration of maintenance fluid

Need for glucose-containing solutions

Hypoglycaemia is common in neonates. Risk factors include prematurity, perinatal stress or asphyxia, being small for gestational age, maternal diabetes, and Wiedemann–Beckwith syndrome. Neonates receiving total parenteral nutrition or glucose infusions are also at risk of hypoglycaemia if the infusion is stopped before or during anaesthesia.4, 5, 8

Long-term exposure to blood glucose concentrations <2.6 mmol L⁻¹ is associated with adverse neurological outcomes.

Guidelines from Germany recommend that, as neonates and preterm infants are at risk of intraoperative hypoglycaemia, blood glucose should be monitored regularly to ensure normoglycaemia. These guidelines recommend that, for healthy term neonates, an isotonic balanced salt solution with glucose 1–2.5% should be used as a background infusion. In small or preterm neonates, and those on parenteral nutrition or with liver disease, an increased glucose concentration may be required.⁷

As isotonic solutions containing glucose 1–2.5% are not readily available in the UK, some use a continuous i.v. set rate glucose infusion through a separate cannula; an additional i.v. cannula is used to give boluses of an isotonic electrolyte solution to compensate for fluid losses associated with surgery. The use of infusion pumps or syringe drivers is recommended to prevent accidental overinfusion.⁴

Tonicity of intraoperative maintenance fluid

Traditionally, hypotonic fluids have been given to neonates for maintenance requirements.⁵ However, hypotonic solutions can lead to hyponatraemia, with potentially devastating neurological sequelae.⁶

There is no current consensus on using isotonic solutions as perioperative maintenance fluids in neonates, because of the concerns about the handling of large Na loads and the lack of evidence.⁴ However, the results of a recent study in neonates have prompted recommendations that balanced isotonic solutions should be considered as routine maintenance fluids.⁹

‘Third space’ losses

Traditionally, ‘hird space' losses were replaced with crystalloid solutions at anything between 1 ml kg⁻¹ h⁻¹ for a minor surgical procedure to 50 ml kg⁻¹ h⁻¹ during surgery for necrotising enterocolitis in premature infants. Recently, the concept of the third space has been questioned, and more restrictive fluid protocols used in adults have been associated with better outcomes.4, 5

Replacement of intraoperative volume losses

Blood volume is estimated as 90–100 ml kg⁻¹ in premature infants, 80–90 ml kg⁻¹ in term neonates, and 70–75 ml kg⁻¹ in infants >3 months of age.⁵ In cases of circulatory instability or blood loss, the goal of treatment is to restore and normalise the circulating blood volume rapidly.⁷ However, the choice of which fluid remains contentious.

A survey of French and British anaesthetists in 2001 showed that the vast majority of responders would use albumin as the colloid of choice in the premature and neonates.¹⁰ Since then, there has been a growing concern about the safety of albumin. The use of albumin as a resuscitation fluid and volume expander may be associated with increased mortality and is no longer advocated. Saline has been shown to be as effective as albumin 5% in treating hypotension in preterm neonates, with less fluid retention in the first 48 h.¹

It is our practice to administer a balanced salt solution to replace intraoperative losses until the transfusion trigger is reached.

Transfusion triggers and practicalities of neonatal transfusion

Neonatal transfusion guidelines for neonatal intensive care (NICU) are based on guidelines for VLBW infants, as there is limited evidence specifically for term infants requiring blood transfusions (Table 2). The British Committee for Standards in Haematology (BCSH) does not make specific recommendations for late preterm infants (>32 weeks gestational age at birth) and term neonates, but suggests that clinicians consider similar thresholds to preterm infants not requiring oxygen.¹¹ In addition, recent Canadian guidelines recommend that neonates should be transfused in situations where there is:

• (i)acute blood loss >10% of the circulating blood volume;
• (ii)haemoglobin <80 g L⁻¹ in a stable newborn with symptoms of anaemia (apnoea, bradycardia, tachycardia, decreased vigour, and poor weight gain);
• (iii)haemoglobin less than 120 g L⁻¹ in an infant with respiratory distress syndrome or congenital heart disease.¹²

Table 2.

Transfusion threshold for preterm neonates (<32 weeks gestational age) according to the requirements for artificial ventilation, oxygen, or CPAP therapy¹¹

Postnatal age	Transfusion threshold (g L−1)
	Artificial ventilation	Receiving O2/CPAP	Not receiving O2
First 24 h	<120	<120	<100
1–7 days	<120	<100	<100
8–14 days	<100	<95	<75–85
>15 days	<85	<85	<85

Goobie and colleagues retrospectively reviewed databases for neonates undergoing non-cardiac surgery and found that postoperative in-hospital mortality significantly was greater in neonates with preoperative haematocrit levels <40%.¹³

Until prospective evidence for specific perioperative transfusion triggers is available, the BCSH transfusion triggers can be used in a surgical setting. Large-volume transfusion, defined as equivalent to a single circulating volume of a neonate over 24 h or 50% of the circulating volume within 3 h, may occur in certain types of high-risk surgery, such as craniofacial surgery and liver surgery. In situations where >40 ml kg⁻¹ of blood loss is anticipated, it is prudent to consider anti-fibrinolytics (such as tranexamic acid) and cell salvage.

There are many formulae to calculate the increase in haematocrit after a given volume of blood transfused. A recent paper provides a much easier and validated method of estimating this. It shows that 1 ml kg⁻¹ of Packed red cells (PRC) will increase the haematocrit by 1%, and that the increase occurs after 15 min and is sustained for 24 h if no further bleeding occurs.¹⁴

There is a risk of hyperkalaemia after large-volume blood transfusion, particularly if infused rapidly through a central venous catheter or small-bore i.v. access. Serum electrolytes should be monitored diligently, including calcium (risk of hypocalcaemia) and potassium. All large-volume transfusions should be administered through a blood warmer to prevent hypothermia.

Platelets

Severe thrombocytopaenia is a common finding in sick neonates in NICU, and the suggested threshold for prophylactic platelet transfusion for neonates having major bleeding or scheduled to undergo major surgery is a platelet count 100 x 10⁹ per litre.¹⁵

Platelets for neonatal transfusion should ideally be:

• (i)ABO identical or compatible, and RhD identical or compatible;
• (ii)cytomegalovirus negative;
• (iii)produced by single-donor apheresis;
• (iv)usually infused in a volume of 10–20 ml kg⁻¹.

Fresh frozen plasma

There is significant uncertainty about transfusion triggers for fresh frozen plasma (FFP) in neonates. Although classical measures of coagulation are prolonged in neonates, this is not necessarily associated with an increased risk of bleeding. Guidelines recommend that FFP be used for vitamin K deficiency with bleeding, disseminated intravascular coagulation (DIC) with bleeding, and congenital coagulation deficiencies when no factor concentrate is available.

The recommended dose for FFP in neonates is 12–15 ml kg⁻¹. FFP for neonatal transfusion should be group AB, or comparable to the recipient's ABO cell antigen.

It is important to note that the national transfusion guidelines state that FFP should never be used as a simple volume replacement, and is not superior to crystalloid or colloid infusions in treating neonatal hypotension.

Cryoprecipitate

The major indications for cryoprecipitate transfusion in infants and children are DIC with bleeding, bleeding after cardiac surgery, and major haemorrhage. The recommended dose is 5–10 ml kg⁻¹, with higher volumes being required if the patient is actively bleeding. In cases of bleeding, monitoring of clinical variables and fibrinogen concentrations is recommended.

The optimum fibrinogen concentration in neonates is not fully understood. In a recent review, Arnold recommends aiming for >1 g dl⁻¹ initially, but setting the threshold at >2 g dl⁻¹ if bleeding subsequently continues.¹⁶

POC testing of coagulation

Thromboelastography is a useful POC test, although specific data in neonates are very limited and are virtually absent in the extremely premature, so results should be interpreted with caution.¹⁷

Sewell and colleagues recommend that the following TEG^® (Haemoscope Corporation, Niles, IL, USA) parameters be used: clotting time, R>6.3; clot kinetics, K>2.5; α angle, α<59; and maximum amplitude, MA<57 as optimal cut-off points for the prediction of clinical bleeding in the neonates.¹⁸

Measuring fluid responsiveness in neonates

In neonatal surgery, the need for fluids has been traditionally inferred by monitoring the heart rate, MAP, oxygen saturation, difference between the core and peripheral temperature, urine output, capillary refill time, lactate, and base deficit. All these variables are notoriously inaccurate in predicting whether a neonate needs fluid.¹⁹

Measures are classified as static and dynamic. Dynamic measures quantify the cardiovascular response to ventilation. The best static measure in the neonate is the stroke volume index measured by transoesophageal Doppler. The most useful dynamic measure that predicts fluid responsiveness in neonates is the ventilation-induced variation in aortic flow velocity, as measured by the transthoracic or transoesophageal echocardiogram. Five studies on the ability of aortic flow velocity to predict fluid requirements in children all have been positive.⁴

Dynamic measures, based on arterial pressure waveform analysis and arterial waveform contour analyses, are not predictive in small infants and neonates because of the difference in the compliance of the neonatal vascular system. The reliability of the variation of the pulse oximetry waveform with ventilation has limited use in the neonate because of the difficulty in establishing a consistent oximetry trace during surgery.

Monitors of end-organ perfusion have been used to titrate fluid therapy in neonates. Arterial near-infrared spectroscopy has shown that a systolic BP decrease of 37% from baseline is associated with significant cerebral desaturation.

Summary

The management of perioperative fluid therapy in neonates requires an appreciation of the physiological, biochemical, and pathological processes involved. A close review of the neonate fluid status in the preoperative period, and an estimation of insensible losses from the skin, viscera, respiratory tract, and urine must be undertaken when replacing fluids. The use of POC tests and monitoring modalities provide a more objective measure to guide the administration of fluids. It must be remembered that neonates are a heterogeneous group in order to administer the right fluid at the right time in the right volume and at the right rate.

Declaration of interest

No conflict of interest.

MCQs

The associated MCQs (to support CME/CPD activity) will be accessible at www.bjaed.org/cme/home by subscribers to BJA Education.

Biographies

Anil Visram BSc FRCA is a consultant in paediatric anaesthesia at the Royal London Hospital. He has interests in neonatal fluids and point-of-care testing.

Renuka Arumainathan FRCA is a research fellow in paediatrics at the Royal London Hospital.

Catalina Stendall FRCA is a locum consultant in anaesthesia at Great Ormond Street Hospital, London.

Matrix codes: 1A01, 2A05, 3D00