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Pediatric Anesthesia ISSN 1155-5645

REVIEW ARTICLE

Fluid homeostasis in the neonate
Frances O’Brien1 & Isabeau A. Walker2,3
1 Department of Paediatrics, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Headington, Oxford, UK
2 UCL Institute of Child Health, London, UK
3 Department of Anaesthesia, Great Ormond Street Hospital NHS Foundation Trust, London, UK

Keywords Summary
neonate; fluids; salt solutions; colloids;
blood transfusion; NICU The physiology of the neonate is ideally suited to the transition to extrauter-
ine life followed by a period of rapid growth and development. Intravenous
Correspondence fluids and electrolytes should be prescribed with care in the neonate. Sodium
Isabeau A. Walker, Department of and water requirements in the first few days of life are low and should be
Anaesthesia, Great Ormond Street Hospital
increased after the postnatal diuresis. Expansion of the extracellular fluid vol-
NHS Foundation Trust, Great Ormond
Street, London WC1N 3JH, UK
ume prior to the postnatal diuresis is associated with poor outcomes, particu-
Email: isabeau.walker@gosh.nhs.uk larly in preterm infants. Newborn infants are prone to hypoglycemia and
require a source of intravenous glucose if enteral feeds are withheld. Anemia
Section Editor: Andy Wolf is common, and untreated is associated with poor outcomes. Liberal versus
restrictive transfusion practices are controversial, but liberal transfusion
Accepted 12 November 2013 practices (accompanied by measures to minimize donor exposure) may be
associated with improved long-term outcomes. Intravenous crystalloids are
doi:10.1111/pan.12326
as effective as albumin to treat hypotension, and semi-synthetic colloids can-
not be recommended at this time. Inotropes should be used to treat hypoten-
sion unresponsive to intravenous fluid, ideally guided by assessment of
perfusion rather than blood pressure alone. Noninvasive methods of assess-
ing cardiac output have been validated in neonates. More studies are required
to guide fluid management in neonates, particularly in those with sepsis or
undergoing surgery. A balanced salt solution such as Hartmann’s or Plasma-
lyte should be used to replace losses during surgery (and blood or coagulation
factors as indicated). Excessive fluid administration during surgery should be
avoided.

particularly in the first few days of life. Intravenous fluid
Introduction
management can be particularly challenging in neonates
In the neonate, fluid homeostasis is determined by the with sepsis or in those undergoing a major surgical inter-
physiological demands of transition to extrauterine life vention. In adult perioperative practice, it is now estab-
and the period of rapid growth and development in the lished that fluid management strategies have an
first few weeks and months after birth. Prematurity important effect on long-term outcomes, and it is likely
imposes additional challenges due to incomplete organ that this is also the case in children, particularly in
development. For the anesthetist, administration of neonates (1,2).
intravenous fluids to maintain cardiovascular stability is This article revises some of the basic physiological
one of the most basic interventions in pediatric anesthe- principles underlying fluid management in neonates, the
sia, yet practical evidence-based guidelines concerning particular considerations of preterm infants, and the
intravenous fluid management are surprisingly difficult changes that occur around the time of birth. We describe
to find. Much of the literature regarding fluid homeosta- a practical approach to intravenous fluid management in
sis in neonates relates to neonatal intensive care (in par- the neonatal intensive care unit and during the perioper-
ticular management of preterm neonates), where it has ative period, including the principles underlying the use
been shown that excessive intravenous fluid is harmful, of crystalloids, colloids, and blood transfusion.

© 2013 John Wiley & Sons Ltd 49
Pediatric Anesthesia 24 (2014) 49–59

and the ECF fluid volume comprises 40% of body mal circumstances. However. and acute Fluid compartments and the capillary endothelial hyperglycemia. Sodium and chloride ions pass freely into the body weight. The endothelial marked hemodilution. ume causing hemodilution and a fall in hematocrit. and this is born out in the renin-angiotensin-aldosterone system. Transmem.6). approximately 100 mlkg1 in preterm by rapid infusion of intravenous fluids. ing plasma and cellular constituents of blood) and the increases transcapillary filtration. water repre- tial fluid. A crystal- (including proteins) between the intravascular and the loid solution also increases hydrostatic pressure and interstitial fluid compartment is crucially dependent on transcapillary filtration. absorption of The vascular endothelium/glycocalyx barrier is freely amniotic fluid through the gastrointestinal tract. it is retained in the intravascular tain the distribution of ions. glycocalyx consists of glycoproteins and proteoglycans containing glycosaminoglycans attached to the endolu- Fluid compartments in the neonate minal surface of the capillary endothelium. Water and sodium homeostasis is main. rather than the (measured and insensible). When intravenous fluid is given brane ion channels and electrochemical gradients main. which (3. naturesis and diure- interstitial fluid via ion channels in the capillary endo. thirst. inflammatory cytokines. The EGL has an important role in inflammation. infants. and the endothe. results in interstitial edema. and antidiuretic hormone. it is retained in the plasma vol- The ECF is divided into intravascular fluid (contain. and movement of water volume initially until hydrostatic pressure increases and across semipermeable cell membranes maintains osmotic filtration into the interstitial space is resumed. sis result in contraction of the interstitial fluid volume thelium. ple intracellular cations and anions respectively.4). major effect on body water composition. O’Brien and I. confer therapeutic benefit. surgery. naturetic clinical studies (see below). but in fetal life. the net result is an increase in vascular glycocalyx model permeability and increased loss of plasma protein. crystalloids should theoretically be as effective as col- tained by the balance between intake and losses loids in hypovolemic fluid resuscitation. As the fetus develops. in the euvolemic state. and regulation of vasomotor tone. Water comprises 60% of lean body mass. thus. and antithrombin III) and may principle anion. the tran- there is a high intracellular protein content. hypoxia. outward hydrostatic pressure from weight (5. 50 © 2013 John Wiley & Sons Ltd Pediatric Anesthesia 24 (2014) 49–59 . potassium and phosphate are the princi. two. Fluid homeostasis in adults has been reviewed recently including albumin into the interstitial space.Fluid homeostasis in the neonate F. equilibrium. scapillary leak ceases. and When capillary hydrostatic pressure is low. representing 60% of plasma. blood flow and later in development. In utero. Early permeable to water. and there is less endothelial glycocalyx layer (EGL). Preterm birth has a throughout the length of the capillary into the intersti. Sodium stances have been shown to protect the EGC (sevoflura- is the principle extracellular cation and chloride the ne. and 80–85% of the body edema. Albumin is contained within the glycocalyx layer. (crystalloid or colloid). semipermeable to albumin. weight of a baby born at 25–30 weeks (7) (see Table 1). if colloid is given peptides. which together form the extent than with a colloid infusion. Movement of fluid displacement of albumin into the interstitium. Various sub- is in the extracellular fluid (ECF) compartment. 90% of the body weight is water. Walker ischemia. the fetus exists in a fluid filled environment— lial glycocalyx layer requires a normal level of plasma the major determinant of fluid balance is placental albumin to function. Contraction of the interstitial fluid volume the lumen of the capillary and the (smaller) inward pull continues through infancy and early childhood such of the colloid osmotic pressure from the capillary results that the adult distribution of total body water is in a continuous net outward leak of protein and fluid obtained by 10 years of age (6). and potentially causes interstitial fluid compartments. and the activity of traditional 3 : 1 volume ratio.A. this is cleared from the interstitial space as sents 90% of the body weight of a baby born at lymph so as to avoid the accumulation of interstitial 23 weeks gestational age (GA). The mately 80 mlkg1 (depending on the time the cord is endothelial glycocalyx (EGC) is fragile and is damaged clamped). hydrocortisone. and under nor. The normal blood volume in the neonate is approxi- hemostasis. This transcapillary leak of thirds of body water is intracellular and about one-third albumin may be greatly increased in shock. but reduces colloid osmotic the capillary endothelium and the overlying capillary pressure so that fluid filtration is increased to a greater endothelial glycocalyx. water comprises 75% of body weight pressure in the interstitial fluid are low. The colloid osmotic pressure and hydrostatic so that by term. and the impermeable to large protein molecules (>70 kDa) in ECF fluid volume is expanded.

the neonate grows rapidly. After the postnatal diuresis. ductus venosus. requirement at 1 month (12. A Cochrane review of randomized controlled studies comparing liberal to restricted water (and Cardiorespiratory adaptation sodium) intake in preterm neonates demonstrated a sig- Birth represents a time of profound physiological nificant increase in postnatal weight gain. Weight is usually at a nadir around day 5. and increased change as placental blood flow ceases and the baby tran. Sodium PDA results in left to right shunt. In the first few drated easily (11). and they may take longer to 36–40 >2500 71–76 ~40 regain their birth weight. particularly in extremely low birth weight infants adaptation after birth (10–14). the renal tubules are short and there is limited as will be described below. Although the kidney has a outcomes (8). High volumes of dilute urine are therefore produced (urinary osmolality 300 mOsmolkg1) at a rate of around 2–3 mlkg1h1 The postnatal diuresis (45–50 mlkg1day1). The postnatal diuresis is centration of urine between 50 and 1400 mOsmolkg1. but most of the fetal lung water is restricted water intake in the first 3 days of life (constant absorbed into the pulmonary capillaries and lymphatics calorie intake) was protective for the development of as the first breaths are taken. Gestational age Body Total body ECF volume but most babies regain their birth weight between 7 and (weeks) weight (BW) (g) water (%BW) (%BW) 10 days. The fetal lungs are filled with bronchopulmonary dysplasia. Patent ductus arteriosus (PDA) is com. Expansion of the ECF by excessive administration of sodium and water. particularly before the postnatal diuresis has occurred. associated with contraction of the ECF due to the loss as in adults (6). and increasing ability to concentrate the urine. intracranial hemorrhage. Oxygen tension rises and PDA. risk of PDA and NEC. tomical closure by 2–3 weeks. with ana. gestational age and severity of illness (14). this tubules. A retrospective chart review of 204 neo- labor. tation. and poorer long-term aldosterone system (RAAS). acidosis. but they have and urine output is low due to the high levels of circulat. increased pulmonary is required for growth and is retained avidly in the distal blood flow and increased risk of chronic lung disease. mon in preterm infants for these reasons and is seen in Renal function is ideally adapted to cope with a liquid 50% of preterm neonates with birth weight <800 g. in most term babies and ‘well’ preterm delayed reduction in ECF. Weight loss of 10–15% may occur in the first week of life during postnatal adaptation in preterm 23–27 500–1000 85–90 60–70 28–32 1000–2000 82–85 50–60 infants (<27 weeks GA). tension rises and. has an adverse effect on out- Neonatal physiology and cardiorespiratory comes.A. fluid.13). O’Brien and I. © 2013 John Wiley & Sons Ltd 51 Pediatric Anesthesia 24 (2014) 49–59 . with a trend to increased risk of sitions to independent life. infants are able to vary the con- results in a brisk diuresis (9). nates <32 weeks GA from a single institution suggested ond stage of delivery. so become dehy- ing vasopressin around the time of birth. The incidence of PDA is affected by intra. Walker Fluid homeostasis in the neonate Table 1 Variation in total body water composition and extracellular of isotonic fluid from the interstitial fluid compartment fluid (ECF) volume at birth in relation to gestational age and body and a reduction in body weight of 5–10% in healthy weight term babies. This period of car. full complement of nephrons from around 35 weeks ges- venous fluid management during this vulnerable period. A random- diorespiratory adaptation also involves closure of the ized controlled trial in neonates <30 weeks GA showed fetal shunts (foramen ovale. liquid is squeezed out of the lungs during the sec. tubules under the influence of the renin-angiotensin- necrotizing enterocolitis (NEC). Neonates are also able to pro- Fluid requirements are low in the first few days of life in duce more dilute urine in the face of a high water load the term neonate.F. Breast-feeding is becoming established (provided ADH levels are not elevated). The ductus arteriosus constricts as oxygen day1) was associated with delayed postnatal diuresis. ability to concentrate the urine (6). is closed functionally by 2 days of life. and production of fetal lung water ceases during and death (11). or in the Renal function in the neonate presence of sepsis. limited ability to concentrate the urine. (milk) diet with relatively low sodium content. which in turn so that by a year of age. Growth of the kidney is associated days after birth pulmonary vascular resistance continues with increasing complexity and length of the renal to fall and pulmonary venous return increases. and ductus that early sodium supplementation (4 mmolkg1 arteriosus). and increased oxygen babies. with the difference remaining after controlling for pulmonary vascular resistance falls. causes release of atrial naturetic peptide. or high circulating prosta- glandin levels. The ductus arteriosus may remain patent if oxygen tensions are low.

Suggestions include alterations in gut perfu- but if the baby is taken out of the incubator (for sion associated with feeding in neonates with hemody- instance for surgery) or if the incubator is left open for namically significant PDA. In adults. particularly the require- for instance from isotonic fluid boluses. Walker Neonates are susceptible to disorders of sodium bal- Nutritional requirements ance. IWL losses may exceed cal interventions (17. and they have a limited ability to retain ated with abnormal neurological outcomes. and how to minimize donor therapy. although a detailed consideration is flushes. Blood glucose falls sodium retention with edema formation. In neonates. Hemostasis in neonates is discussed else- if a neonate receives unhumidified oxygen via nasal where in this journal and will not be considered here cannulae. protected from damage due to hypoglycemia. and drugs. and blood glucose should be Insensible water loss in neonates monitored (15). Aldosterone secre. and the skin in the most preterm neonates siveness to erythropoietin in the neonate. IWL from the skin varies with gestational age. poor skin is associated with cooling due to the effect of the weight gain. Inadequate sodium neonates are at risk of hypoglycemia if enteral feeding is intake is associated with severe hyponatremia and poor delayed (for example.6 mmoll1 is associ- less active. renal water losses (15). However. Interestingly. and surgi- In extreme preterm infants. respiratory IWL may be high exposure. particularly in extreme may be reduced by nursing preterm infants <2 weeks of preterm neonates. O’Brien and I. ents of blood transfusions. This is particu. and both sodium and water content in intravenous fluids need to be considered carefully. Difficulty in keeping a baby It has also been suggested that prior blood transfusion warm may be an indication of excessive IWL. so are relatively thereafter will result in hyponatremia. repeated blood samples in the NICU.18). but rises in the first few hours in mended that neonates are given sodium-free fluids until response to endogenous glucose production or feeding. partly due more preterm the infant.A. Evaporation of water from the Untreated anemia is associated with apnea. intravenous ments for glucose. insensible water loss (IWL) consists mostly of water lost via evaporation through the skin (two- Blood transfusion thirds) or respiratory tract (one-third). Postextubation. and rapid is thin and fragile and poorly keratinized.13). what should be babies receiving nasal CPAP or nasal ‘high flow’ the target hemoglobin. limited respon- weight ratio. iatrogenic anemia from IWL and can have a significant affect on fluid balance. after the postnatal diuresis to allow for contraction of Neonates metabolize ketones as well as glucose as an the ECF volume (12. and long-term neurological outcomes in preterm neonates they have limited glycogen stores. the greater the transepidermal to the transition from synthesis of fetal hemoglobin to water loss as there is a higher body surface area to adult hemoglobin A that starts at birth. larly important in preterm neonates as the RAAS is prolonged hypoglycemia below 2. or immunological mechanisms associated with loss decreases as preterm neonates mature. not clear. this protection will be lost.20). sepsis. the severity of preexisting procedures. and may result in hypernatremia or beyond the remit of this article. immediately after birth. The tion (19.Fluid homeostasis in the neonate F. to reduce the risk of NEC). primarily related of the quality of nursing care in a neonatal intensive to misidentification (lack of wrist bands). from nutritional requirements. tionately represented in the UK Serious Hazards of ture instability in preterm infants are good indicators Blood Transfusion reporting system. but inadequate sodium intake important energy substrate in the brain. Insensible water anemia. and over care unit. Use of a growth. As neonates are such frequent recipi- Humidification reduces IWL from the lungs in venti. Fluid requirements cannot be considered in isolation tion is slow to be reduced in the face of a sodium load. 52 © 2013 John Wiley & Sons Ltd Pediatric Anesthesia 24 (2014) 49–59 . the Anemia is common in neonates in the NICU. neonates are also dispropor- incidence of hypernatremic dehydration and tempera. IWL may be a risk factor for NEC. and poor neurodevelopmental outcomes. latent heat of evaporation. Intravenous glucose (16). although the precise mechanism is age in a heated humidified incubator (>80% humidity). should be provided to babies at risk of hypoglycemia at a starting rate of 5–7 mgkg1min1 (10% dextrose 70–100 mlkg1day1). transfusion (18). It is recom. and ambient the transfusion of red cells without leukocyte deple- humidity may be gradually decreased with time. and humidification is also required for trigger for transfusion should be used. (21). Anemia is also related to timing of clamping of radiant warmer or phototherapy significantly increases the umbilical cord at birth. Preterm sodium in the distal renal tubule. questions arise as to what lated babies.

with semi-synthetic colloids Age >1 week <110 commonly used. and albumin mainly used for neonates Oxygen therapy/CPAP (34). ill children and neonates (30): limiting blood sampling to a minimum. and challenges associated with mea- is required for those with immune deficiency (e. Tra- practical guidelines have been suggested (see Table 2) ditionally. Reduction in apnea and brain injury was not delivery. the management of hypotension. Walker Fluid homeostasis in the neonate Measures suggested to reduce exposure of neonates to suspected 22q11 deficiency) to avoid graft versus host blood transfusion include delayed clamping of the disease. as described above. Inter- in the UK are leucodepleted. © 2013 John Wiley & Sons Ltd 53 Pediatric Anesthesia 24 (2014) 49–59 . O’Brien and I. and is associated with worse long-term out- confirmed in a large multicentre study (Preterm Infants comes (32). In the meantime. reduced hemoglobin a given level has been evaluated in critically incidence of NEC and intraventricular hemorrhage). reduce tissue oxygen (24. Excessively high hematocrit (>65%) should be avoided and improved long-term neurodevelopmental outcomes as this will increase blood viscosity. A In the randomized controlled study by Bell and single-center randomized controlled study of restrictive colleagues. Curley A et al. and increased mortality. adult packs should be split into smaller ‘pedi. some developmental outcomes.A. but further trials were A major concern in the neonatal intensive care unit is required to look at long-term impact (27). 136 gl1) (31).23). Table 2 A practical guide for transfusion in the neonate (modified from Venkatesh V. PINT study) (26). NEC. particularly in preterm domized controlled study is currently under way to look infants in the first few days of life. apnea.F. the following formula to umbilical cord at birth (also associated with greater calculate the volume of blood required to raise the cardiovascular stability in preterm infants. For the anesthetist. from CMV negative. due to improved oxygen delivery). with isotonic fluid replacement. and other abnormal Indication for transfusion hemoglobin (gl1) losses (such as nasogastric tube losses). How do we decide when a Volume expansion – crystalloid versus colloid neonate needs a transfusion. Recent publications have challenged the use of Age <1 week <100 semi-synthetic colloids and suggested caution regarding Age >1 week >90 the use of albumin and excessive volumes of intrave- No respiratory support. depending ¼ required rise in Hb ðg  dl1 Þ  weightðkgÞ  4:8 ð1Þ on the level of respiratory support required (22. blood transfusion reduced cardiac output in versus liberal transfusion in preterm neonates did not neonates who were anemic (Hb 91 gl1) (presumably affect donor exposure (there was a single-donor pro. stable nous crystalloid in perioperative or critically ill patient Age >1 week ≤75 (35). useful target for transfusion in the intraoperative period. mal hemorrhage. and selection of lower threshold hemoglobin values for transfusion. Approaches to the treatment packs’ (36–66 ml) to minimize donor exposure.. surement of cardiac output rather than simple measure- ment of blood pressure (33). ventions to improve long-term outcomes are hampered low antibody titer repeat donors. hemoglobin of 120–140 gl1 serves as a icy was associated with a lower incidence of parenchy.25). gestational age in mmHg). A survey of specialist pediatric anes- Blood loss or anemia immediately 120 thetists in 2001 suggested that the choice of fluids for after birth Ventilated plasma volume expansion in infants and children varied Age <1 week <120 by geographical location. but this effect is not gram to split adult donor units into smaller pediatric seen in infants with a higher starting hemoglobin (Hb packs) and suggested that a more liberal transfusion pol. the definition of hypotension in a preterm (29). Low cardiac output at the effect of transfusion thresholds on long-term neu. according to Volume of packed red cells (ml) protocol. infant is taken as MAP <30 mmHg (or equivalent to the Ideally. all neonatal transfusions of crystalloid or colloid. and in of hypotension include volume expansion with boluses addition to routine screening. in Need of Transfusion. A large ran. worse long-term neuro- infants (the ETTNO study) (28).g. periventricular leukomalacia. and hypotension are associated with increased risk of rocognitive outcome in extremely low birth weight intracranial hemorrhage. Irradiated blood by lack of evidence. Brit J Haematol 2013 160: 421–433) Hypovolemia due to acute blood loss is logically treated Suggested with blood. optimizing nutrition. A Cochrane review concluded that a restrictive transfusion policy Management of hypotension was associated with moderate reduction in transfusion with no increased short-term risk. or the use of inotropes. Khan R.

these solutions cannot be recommended. The Fluid Expansion as Supportive Therapy disturbance. and the authors recommended that saline should be used in preference to colloid for treat- Which crystalloid solution? ment of hypotension in this situation. notable in the FEAST study that both albumin and saline groups were associated with worse outcome at Use of inotropes 48 h than the no-fluid bolus control group. or gelatin) (36). The SAFE and FEAST studies volumes of balanced salt solutions may be associated also demonstrated the same clinical effectiveness for with hyponatremia or high lactate concentration (Hart- similar volumes of saline or albumin. O’Brien and I. Walker A Cochrane review of eight randomized controlled updated Cochrane review of albumin for resuscitation studies did not show any benefit of routine volume and volume expansion in critically ill patients again con- expansion to improve outcomes in preterm infants. and tions in neonates is also limited. plasma.41). There were no differences in seem prudent to avoid large volumes of gelatins in long-term outcome (inotropic support. sure <25 mmHg for infants with birth weight 1 kg. gelatin.49 kg. higher than physiological concentration of sodium and tor of worse long-term outcomes and suggested that chloride ions. lung disease) (39). but adult patients in ICU suggested increased mortality found no difference in outcome at discharge or after and/or need for renal replacement therapy at 90 days in 2-year follow-up (37. acid-base sepsis (42). incidence of acute kidney injury where HES or gelatin tension. low BP. A prospective sequen- <35 mmHg for infants with birth weight 1. restricted chloride containing solutions (Plasma-lyte. chronic neonates. One small study compared the patients receiving HES (46. although subsequent analysis suggested there adults undergoing open abdominal surgery showed may have been a potential benefit in patients with severe fewer major complications (blood transfusion. The recently refill. anced salt solution (Plasma-lyte) compared with 0. and on the basis of infants.9% saline. and it would also retention in the first 48 h. and metabolic acidosis. Ringers). postoperative infection.35).A. many clinicians have preferred ‘bal- fluid regimens in the perinatal period showed that anced salt solutions’ such as Hartmann’s or Ringers colloid infusion (as albumin or fresh frozen plasma if Lactate in anesthetic practice. but albumin was associated with more fluid was used compared crystalloids (49). chloride-poor 20% albumin) suggested the topic (35). review of a large database of 28 days. and theoretically. fresh frozen such as saline (45). Normal saline contains a coagulation was abnormal) was an independent predic. renal impairment) (FEAST) study suggested no difference in outcome and improved mortality in those who received a bal- between saline versus albumin boluses for children pre.4. The information on outcomes after use of gelatin solu- <30 mmHg for infants birth weight 1–1.5–1.Fluid homeostasis in the neonate F.9% senting with febrile illness suggestive of severe sepsis. Studies in very low birth weight preterm neonates randomized to two For many years. However. The largest study considered Two recent large randomized controlled studies com- volume expansion within 2 h of birth with fresh frozen paring 6% hydroxyethyl starch (HES) (130/0. Hypotension was defined as mean arterial pres. An observational study of patients in an adult ICU Randomized controlled studies in adult practice and where there was a change from high chloride containing older children have helped throw further light on fluid solutions (0.38).99 kg. or cardiotoxicity due to high acetate theoretical considerations (3. firmed no overall benefit of albumin versus crystalloids using normal saline or colloid (albumin. period (40. The saline versus albumin fluid evaluation low chloride containing solutions were associated with study (SAFE) for fluid resuscitation in adult intensive less acute kidney injury and need for renal replacement care suggested no difference in overall mortality at therapy (50). which has challenged the concept of acute volume resuscitation in Clinical signs of low perfusion include delayed capillary children with compensated shock (44). Safety information on effect of saline 10 mlkg1 compared with 5% albumin long-term outcomes after use of starch solutions in 10 mlkg1 for treatment of hypotension in preterm neonates is extremely limited (48).47). albumin in saline) to choices for intravenous volume resuscitation. but there is a 54 © 2013 John Wiley & Sons Ltd Pediatric Anesthesia 24 (2014) 49–59 .42) to plasma or gelatin compared with maintenance infusion Ringers lactate or saline for volume resuscitation in of 10% dextrose to prevent cerebral hemorrhage. and read. death. ers are referred to a recent comprehensive review on this Hartmann’s. The balanced salt solutions do not contain although this study excluded neonates and patients the same ion content as plasma. as predicted from mann’s. high undergoing surgery (43). the adult data. saline (51). which may result in hyperchloremic acido- colloids should be used with caution in the perinatal sis and adverse effects on renal or immune function (35). Similarly. tial comparison study in adults suggested increased Saline was as effective as albumin in treating hypo. it was concentration (Plasma-lyte) (35).

sunken anterior fontanel. inotropes should only siveness more reliably than clinician assessment.g. account of the maintenance requirement for water and infrared spectroscopy (NIRS) for measuring regional electrolytes. and the length of stay compared but associated with a low blood pressure. to prevent chronic lung disease. urine output. Extremely preterm dehydration older babies and children (e. circumstances. should be TED has also been used in neonates and infants 2. decreased stroke volume. these results may reflect maternal values. dry mucous mem. Intravenous fluid prescriptions in the NICU need to be Noninvasive methods of assessing cardiac output individualized according to the gestational age. or low cardiac undertaken to assess ventilation and adequacy of perfu- output associated with myocardial dysfunction or sep. Urinary electrolytes and specific gravity can be sis. milrinone). Clinical signs such as indicate the need for a more generous fluid intake. sion. but normal perfusion. TED has be individualized and inotropes associated with systemic been shown to provide an accurate assessment of car- vasodilatation (dobutamine. Similarly. Hemodynamic monitoring in neonates Laboratory assessment Cardiac output and perfusion are traditionally inferred Term neonates who are sick and preterm babies will from clinical signs such as blood pressure. urea. the need for lar resistance usually falls. and comorbidities. heart rate. the presence of hypernatremia may ularly preterm infants. critically low perfusion in a preterm infant geal Doppler monitor in adults undergoing major or may be associated with relatively high afterload.. central require daily measurement of serum electrolytes. high-risk surgery. systemic vascu. hyponatremia is commonly seen in babies surements of base excess. after 24 h. Use of the TED was associated with positive pressure ventilation. and transesopha- pressure and systemic perfusion as some babies may geal Doppler (TED) (52).. partic. Examples include near. In capillary refill time. reduction in postoperative complications. and © 2013 John Wiley & Sons Ltd 55 Pediatric Anesthesia 24 (2014) 49–59 . The National Institute for have normal blood pressure but low perfusion. and lactate. delayed cap- illary refill occurs in low cardiac output states. or a side effect of caffeine therapy used interpretation of results difficult. increased heart rate may also be a reflec. or low Health and Care Excellence medical technologies guid- blood pressure. 8 hourly) as they can rapidly become dehy- branes) are not generally useful in the newborn. Swings in blood in response to fluid loading or changes in inotropes (54). Clinical signs are notoriously mally declines postnatally. and some. pulse maintain cardiac output and tissue oxygen delivery. oxygen saturation. transfusion and volume requirements to perfusion in the brain and splanchnic circulation. measured either routinely or depending on clinical tion of pain. so perfusion may be normal central venous access. O’Brien and I. to a fluid challenge (55). In the first 24 h ance supported the use of the CardioQ-ODM esopha- after birth. Rou- tachycardia may imply dehydration. the first 24 h. but it Intravenous fluid and electrolyte prescription in can also be seen in infants with peripheral vasoconstric- the NICU tion from cold stress. Prescriptions should take increasingly in clinical practice. epinephrine) should be chosen thermodilution and can track changes in cardiac output according to the clinical situation (33). acidosis.A. Care needs to with conventional clinical assessment (53). rather than authors suggested that the use of the TED may guide based on an arbitrary value of blood pressure. postna- have been validated in children and are being used tal age. serum creatinine nor- saturation. and creatinine in the early days following delivery. drated due to IWL. or pressor diac output in children of all ages when compared with agents (dopamine. exacer. lytes (e. core-peripheral tem. venous pressure (CVP). discomfort. or where invasive monitoring would bated by left to right flow through a patent duct and be considered. pyrexia. diuretics such as furosemide may make light). for instance. pressure.5– avoided as this is thought to be associated with intra. such as signs. altered skin babies will need more frequent measurement of electro- turgor. particularly in preterm infants. Ideally. supplemented by laboratory mea. 5 kg undergoing surgery and to identify fluid respon- ventricular hemorrhage. the be used if there are signs of poor perfusion. echocardiography. tine blood gas analysis and lactate measurement are cular volume. Walker Fluid homeostasis in the neonate poor correlation between low systemic arterial blood contour analysis. environmental stress (noise. reduced intravas. mixed venous oxygen whose mothers received oxytocin.F.g. and deci. appropriate fluid management during surgery and sions about fluid loading versus use of inotropes should would help avoid excessive fluid boluses in neonates ideally be made using some form of assessment of where there is no increase in cardiac output in response cardiac output. but these changes may be inaccurate. and drugs that cause vasoconstriction. used to identify delayed in extremely preterm babies. However. perature difference.

Day 4 120–150 180 ally 5–10 mlkg1day1. especially if under radiant warmers. especially in the preterm neonate. stool) and insensible water loss (IWL). during active growth. Fluid intake calculations should take all sources Conversely. blood pressure. They are unable to severe respiratory distress receiving muscle relaxants to effectively retain bicarbonate and are unable to ade- facilitate ventilation may become very edematous due to quately acidify their urine. <1. restricted until the postnatal diuresis has taken place. low Fluid balance urine output. very low birth weight which 70–80% is water. As the baby grows. as for any other drug. 56 © 2013 John Wiley & Sons Ltd Pediatric Anesthesia 24 (2014) 49–59 .Fluid homeostasis in the neonate F. rising urine specific gravity. This may lead to the develop- accumulation of interstitial fluid. Urine output is measured by weighing nappies or by measuring urine collected in urinary bags or Electrolyte requirements by catheter. Walker nutritional requirements.5 kg. first few days of life After the first week of life. so intravenous fluid should be increased. loremic acidosis. Extremely preterm infants (who are well) require NEC.) may result in hyperch- particular challenge. Total fluid requirement includes the maintenance the requirement for sodium and potassium increases. extremely low birth weight <1 kg. may occasionally require more than 200 mlkg1day1 during the first 2–3 days of life. Urine output may be low or absent in the first 24 h after birth.5 kg. Stool water is usu. requirement to replace measured losses (urine. individual basis. depending on gestational age and trolytes and urine output (and consideration of disease associated medical problems. a urine output of Day 2 70–80 120 approximately 60–80 mlkg1day1 is required to Day 3 100–120 150 excrete the urinary renal solute load. intravenous fluid should be reduced if of fluid into account. status). For these reasons. above. for instance in sepsis. Errors in fluid management may result in serious morbidity. radiant warm. or pul. fluid boluses. Day 5 150–180 180 weight gain for normal growth is 10–15 gkg1day1. need to be fine-tuned according to measurement of elec- monary fluid. birth Insensible water loss is high in the first few days of life weight. IWL can be estimated using the following formula: but it is also important to maintain intravascular vol- IWL ¼ fluid intake – urine output ume and to keep physiological variables such as heart þ weight loss (or – weight gain) ð2Þ rate. Babies with additional sodium supplements. serum sodium concentration suggests inadequate fluid mented by regular clinical assessments as described administration. Greater weight loss than expected. and the fluid require- ment for growth. ment of a metabolic acidosis. Quantifying and man. increased body temperature. O’Brien and I. sodium is often given in the form of sodium acetate in total parenteral nutrition (TPN) and additional sodium bicarbonate Maintenance fluid and electrolyte requirement in the may be given to replace renal losses of bicarbonate. or respiratory distress syndrome. After the first 24 h. but thereafter should be at least Day 0–1 50–60 80–90 1 mlkg1h1. Extremely preterm infants. Sudden or large increases in weight requires 2–3 mmolkg1day1 of sodium and 1–2 generally reflect fluid retention with abnormal distribu. Table 3 Volume of fluid required according to gestational age. as fluid boluses etc. and postnatal age and is further increased by prematurity. Excessive administration aging reduced cardiac output due to intravascular fluid of sodium chloride (given as flushes for IV cannulae. and appropriately or actually increased following delivery. supple. and The fluid requirements for well term and preterm intravenous fluids need to be prescribed carefully. VLBW. milk. particularly to maintain blood Insensible water loss cannot be measured but should glucose. Depending on gestation. bowel. or weight did not decrease parenteral nutrition. Fluid requirement (mlkg1 day1) ers. Sodium (or potassium) is rarely required in the first Regular measurement of weight is important to assess 24 h of life.A. of LBW. and some types of Postnatal day Term/LBW VLBW/ELBW phototherapy. mmolkg1day1 of potassium. to volume depletion in the presence of tissue edema is a carry drugs. and/or rising An accurate record of fluid balance is essential. drug infusions. Drain losses should also be taken into consideration. Sodium and water intake should usually be be estimated to allow for appropriate fluid prescription. serum sodium is falling. and urine output stable. on an babies are shown in Table 3. low birth weight <2. including intravenous crystalloid. Supplementation will tion of fluid due to increase in interstitial. a newborn baby overall fluid balance. ELBW.

and compli. This is and should be well-hydrated. an arbitrary allowance has also been made for for many weeks. replacement fluids. ‘Resuscitation’ fluids were defined ate care (warmed humidified gases. great volume. Many neonates. Intravenous fluid is given to pro. There was a 59% reduction in complica. with frequent analysis of hematocrit. in the term neonates with NEC. and this should be an area for future research. and reduction in length of stay of 3 days in glucose should be monitored carefully. and blood glucose. and infusions through these lines should not be stopped Inadequate or excessive fluid administration during in theater.A. but ment. to maintain blood lactate. and line-related sepsis is a major con- unquantifiable ‘third space losses’. The glucose requirement during surgery is less than tive’ if fluid was given at less than maintenance require. The Canadian Pediatric Water requirement during surgery Surgery Network (CAPSNet) published an analysis of the CAPSNet database describing preclosure fluid Maintenance requirement for water during surgery is resuscitation in 407 live-born neonates with gastroschi. and an increase risk of bacteremia. a condition typically associated fluid loss from low. glucose containing fluids. indicated). gests that the goal should be ‘enough but not too much’ (1). and all central lines should be accessed with an aseptic vide maintenance requirements and replace fluid losses. every 17 mlkg1 resuscitation fluid. base excess. On a practical note. maintenance due to the stress response to surgery. intraoperative fluid management is usually based on the maintenance requirement for intravenous fluid with replacement of measured losses.4). The authors concluded that. as fluid boluses (in mlkg1) in excess of the standard In preterm infants. Meta. may be dependent on TPN past. particularly pre- and to support the blood pressure if required. similarly. In practical terms. and there are those who need even first few days of life will be managed in the neonatal unit more (sometimes up to 12 mmolkg1day1). and fluid homeostasis.F. than fluid ‘imbalance’. ‘restric. and partly due to inability to retain sodium. there was one additional day of ventilation. so it is difficult to give precise Many preterm infants may require 6–8 mmolkg1 guidance. Blood tions. The authors defined fluid regimens as ‘bal- Glucose requirements during surgery anced’ if the volume of perioperative fluid was based on the daily maintenance requirement for fluid. blood glucose can be maintained in the normal range by tionship between fluid given. or ‘liberal’ if the regimen was associated with interruption of glucose infusion during surgery is associ- fluid loading. There was a dose–response rela. warming blankets). nontouch technique. tain oxygen delivery to the tissues. and continu- Fluid and electrolyte requirements during surgery ous clinical assessment to determine adequacy of perfu- The aim of perioperative fluid management is to main. Most neonates presenting for surgery in the day1 of sodium. but this concept is no cern. avoid hypoglycemia. Our practice is to continue the maintenance © 2013 John Wiley & Sons Ltd 57 Pediatric Anesthesia 24 (2014) 49–59 . There are very few studies describing periopera. fully resuscitated. and to care should be taken with intravenous lines in neonates. weight gain. or a low-dose patients managed in a state of fluid ‘balance’ rather glucose infusion continued (57). In practice. Peripherally inserted long lines are easily blocked. and separate intravenous lines analysis of randomized controlled trials of fluid therapy are required for maintenance glucose and isotonic in major elective open abdominal surgery in adults sug. ated with an increased risk of hypoglycemia. low as vasopressin levels are raised and urine output is sis. Walker Fluid homeostasis in the neonate 3–5 mmolkg1day1 of sodium and 2–3 mmolkg1 There are very few studies regarding intraoperative day1 of potassium being the usual amounts required. which has the advantage of Multivariate outcomes analysis demonstrated that for minimizing insensible fluid losses. Insensible losses should be minimized by appropri- exposed bowel (2). neonatal intensive care unit. as for standard neonatal care. longer valid (3. surgery is often undertaken in the maintenance dextrose infusion of 60–80 mlkg1day1. O’Brien and I. but may also be receiving intravenous maintenance fluids with glucose. Replacement fluid should be provided in the form of an ‘routine’ fluid boluses in euvolemic infants should be isotonic balanced salt solution such as Hartmann’s or avoided and should only be given in response to Plasmalyte (or blood or fresh frozen plasma/platelets as hypovolemia. fluid losses in neonates. continuing maintenance 10% infusion at a reduced rate cations in patients receiving liberal fluids in one study or by the use of 1–2% glucose in isotonic solution as (56). organ perfusion. sion. tive fluid management in neonates. care should be taken not to bolus surgery may be associated with poor outcomes. TPN and length of hospi- Replacement fluids during surgery tal stay. secondary to the use of diuretics. maintenance fluid (58).

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