Table 2.
Summary table of studies included to produce recommendations and their SIGN level of evidence
| Study: author and year of publication | Study examined | Study design settings and location | Patient population | Summary of results | Risk of bias | Applicability to our question/patients | SIGN level of evidence |
|---|---|---|---|---|---|---|---|
| Mackenzie et al. (1991) |
PICO 1 IV vs enteral hydration with electrolyte solutions |
RCT Single centre Australia |
104 dehydrated acutely ill children with gastroenteritis | No difference | Serious risk | High | 1− |
| Nager et al. (2002) |
PICO 1 IV vs enteral hydration with electrolyte solutions |
RCT Single Centre United states of America (USA) |
90 dehydrated acutely ill children with gastroenteritis | Higher costs in IV group | Serious risk | High | 1− |
| Sharifi et al. (1985) |
PICO 1 IV rehydration vs enteral rehydration |
RCT Single Centre Iran |
470 dehydrated acutely ill children with gastroenteritis | Less hyponatremia, acidosis hypokalaemia, diarrhoea, and higher weight gain in enteral group | Serious risk | High | 1− |
| Spandorfer et al. (2005) |
PICO 1 IV rehydration vs enteral rehydration |
RCT Single Centre USA |
73 dehydrated acutely ill children with gastroenteritis | No difference | Serious risk | Moderate | 1− |
| Rao et al. (2020) |
PICO 1 IV hydration vs enteral feeding |
RCT Single Centre India |
186 Critically ill term neonates on inotropes | No difference | Low risk | High | 1 + + |
| Oakley et al. (2013) |
PICO 1 IV vs enteral hydration or enteral feeds |
RCT Multicentre Australia and New Zealand |
759 acutely ill bronchiolitis children | No difference | Serious risk | High | 1− |
| Oakley et al. (2017) |
PICO 1 IV vs enteral hydration or enteral feeds |
RCT Multicentre Australia and New Zealand |
759 acutely ill bronchiolitis children | Higher costs in IV group | Serious risk | High | 1− |
| Duke et al. (2002) |
PICO 1 100% 0,45%NaCl-G5 IV, vs 60% breast milk |
RCT Multicentre Papua New Guinea |
357 acutely ill children with meningitis | Improved outcomes in IV hydration group | Serious risk | Moderate | 1− |
| Saeidi et al. (2009) |
PICO 1 Breast milk + IV hydration, vs breast milk |
RCT Single Centre Iran |
100 term neonates requiring phototherapy for hyper-bilirubinemia | Bilirubin levels decreased faster in the IV group | Serious risk | Moderate | 1− |
| Wilson et al. (1990) |
PICO 1 IV vs no IV hydration |
RCT Single Centre United Kingdom |
50 children undergoing tonsillectomy | No difference | Serious risk | High | 1− |
| Easa et al. (2013) |
PICO 1 EN feeds with supplemental IV hydration, vs EN feeds or EN hydration |
RCT Single Centre Iraq |
64 term neonates requiring phototherapy for hyper-bilirubinemia | No difference | Serious risk | Moderate | 1− |
| Szabo et al. (2015) |
PICO 1 NPO + low IV hydration, Vs NPO + high IV hydration, Vs PO + low IV hydration, Vs PO + high IV hydration |
Retrospective cohort study Single Centre USA |
201 acutely and critically ill children with pancreatitis | Improved outcomes in the PO + high IV hydration group | Good quality | Moderate | 2 + |
| McNab et al. (2015) |
PICO 2 Isotonic (Plasmalyte-G5%®) vs Hypotonic ((G5%- NaCl 0,45%) |
RCT Single Centre Australia |
641 acutely ill children | Lower risk of hyponatremia in isotonic group | Serious risk | Moderate | 1− |
| Lehtiranta et al. (2021) |
PICO 2 Isotonic (Plasmalyte-G5%®) vs Hypotonic (G5%- NaCl 80 mmol/L) |
RCT Single Centre Finland |
614 acutely ill children | No significant difference in natremia | Serious risk | Moderate | 1− |
| Coulthard et al. (2012) |
PICO 2 and PICO 3 and PICO 5 Hartmann-G5% full maintenance vs 0.45NaCl-G5%, 2/3 of Holliday and Segar formula |
RCT Single Centre Australia |
82 critically ill children after neurosurgery |
smaller postoperative fall in plasma sodium in Hartmann-G5% group No difference in Cl and HCO3 plasma levels No data support the effect of rate/amount due to mixed intervention |
Serious risk | Low | 1− |
| Almeida et al. (2015) |
PICO 2 Isotonic (0.9%NaCl) vs hypotonic (0.45%NaCl) IV-MFT |
RCT Single Centre Portugal |
233 critically ill children | Lower risk of hypernatremia with 0.9% saline than hyponatremia with 0.45% | Serious risk | Moderate | 1− |
| Bagri et al. (2019) |
PICO 2 Isotonic (0.9%NaCl) vs hypotonic (0.45%NaCl) IV-MFT |
RCT Single Centre India |
150 acutely ill children | lower serum osmolarity at 48 h in the hypotonic group | Serious risk | High | 1− |
| Castilla et al. (2019) |
PICO 2 Isotonic (0.9%NaCl) vs hypotonic (0.30%NaCl) IV-MFT |
RCT Single Centre Spain |
130 critically ill children after surgery | Lower risk of hyponatremia in isotonic group | Serious risk | High | 1− |
| Choong et al. (2011) |
PICO 2 Isotonic (0.9%NaCl) vs hypotonic (0.45%NaCl) IV-MFT |
RCT Single Centre Canada |
258 acutely and critically ill children after surgery | Lower risk of hyponatremia in isotonic group | Low risk | High | 1 + + |
| Flores et al. (2016) |
PICO 2 Isotonic (G5%-NaCl 0,9%) vs Hypotonic (G5%- NaCl 0,45%) vs Hypotonic (G5%- NaCl 0,3%) |
RCT Single Centre Mexico |
163 acutely ill children | Lower risk of hyponatremia in isotonic group | Low risk | Moderate | 1 + |
| Friedman et al. (2015) |
PICO 2 Isotonic (G5%-NaCl 0,9%) vs Hypotonic (G5%- NaCl 0,45%) |
RCT Single Centre Canada |
110 acutely ill children with acute respiratory diagnosis | No significant differences | Low risk | High | 1 + |
| Kannan et al. (2010) |
PICO 2 & PICO 5 Isotonic (G5%-NaCl 0.9%) vs Hypotonic (G5%- NaCl 0.18%) vs Hypotonic (G5%- NaCl 0.18%%) lower infusion rate |
RCT Single Centre India |
167 acutely ill children |
Less hyponatremia in isotonic group Less hyponatremia in the restrictive group |
Moderate risk (serious) | High (moderate) |
1 + (1−) |
| Kumar et al. (2020) |
PICO 2 Isotonic (G5%-NaCl 0,9%) vs Hypotonic (G5%- NaCl 0,45%) |
RCT Single Centre India |
168 acutely ill children | No difference | Moderate risk | Moderate | 1− |
| Montanana et al. (2008) |
PICO 2 Isotonic (NaCl 140 mmol/L) vs Hypotonic (20–100 mmol/L Na) |
RCT Single Centre Spain |
122 critically ill children | Increased risk of hyponatremia in hypotonic group | Serious risk | High | 1− |
| Pemde et al. (2015) |
PICO 2 Isotonic (NaCl 0,9%) vs Hypotonic (G5%- NaCl 0,45%) |
RCT Single Centre India |
92 acutely ill children with central nervous system infection | Less Hyponatremia in the isotonic group | Serious risk | Low | 1− |
| Ramanathan et al. (2016) |
PICO 2 Isotonic (NaCl 0,9%) vs Hypotonic (NaCl 0,18%) |
RCT Single Centre India |
119 acutely ill children with pneumonia | Increased risk of hyponatremia in hypotonic group | Serious risk | Moderate | 1− |
| Rey et al. (2011) |
PICO 2 Isotonic (NaCl 156 mmol/L) vs Hypotonic (50–70 mmol/L Na) |
RCT Multicentre Spain |
125 critically ill children | Increased risk of hyponatremia in hypotonic group | Serious risk | Low | 1− |
| Saba et al. (2011) |
PICO 2 Isotonic (G5%-NaCl 0,9%) vs Hypotonic (G5%- NaCl 0,45%) |
RCT Single Centre Canada |
37 acutely ill children requiring IV-MFT | No difference | Serious risk | Moderate | 1− |
| Torres et al. (2019) |
PICO 2 Isotonic (G5%-NaCl 0,9%) vs Hypotonic (G5%- NaCl 0,45%) |
RCT Single Centre Argentina |
294 acutely and critically ill children requiring IV-MFT | Increased risk of hyponatremia in hypotonic group | Serious risk | Low | 1− |
| Jorro Baron et al. (2013) |
PICO 2 Isotonic (NaCl 154 mmol/L) vs Hypotonic (77 mmol/L Na) |
RCT Single Centre Argentina |
63 critically ill children | Higher Na Plasma levels in isotonic group | Serious risk | High | 1− |
| Tuzun et al. (2020) |
PICO 2 Isotonic (G5%-NaCl 0,9%) vs Hypotonic (G5%- NaCl 0,45%) |
RCT Single Centre Turkey |
108 critically ill term neonates | Lower plasma Na Change in isotonic group | Serious risk | Low | 1− |
| Velasco et al. (2018) |
PICO 2 Isotonic (NaCl 154 mmol/L) vs Hypotonic (51–77 mmol/L Na) |
Retrospective cohort Single Centre Spain |
111 critically ill children | Less hyponatremia risk in isotonic group | Good quality | High | 2− |
| Da Silva Vadalao et al. (2015) |
PICO 2 Isotonic (NaCl 0,9%) vs Hypotonic (NaCl 0,18%) |
RCT Single Centre Brazil |
50 acutely ill children after appendicectomy | No difference | Critical risk | Low | 1− |
| Carandang et al. (2013) |
PICO 2 Isotonic (any type) vs Hypotonic (any type) |
Retrospective cohort Single Centre USA |
1048 acutely ill children | Increased risk of hyponatremia in the hypotonic group | Poor quality | Low | 2− |
| Golshekan et al. (2016) |
PICO 2 Isotonic (G5%-NaCl 0,9%) vs Hypotonic (G5%- NaCl 0,45%) |
RCT Single Centre Iran |
75 acutely ill children | Increased risk of hyponatremia in the hypotonic group | Critical risk | Low | 1− |
| Karageorgos et al. (2018) |
PICO 2 Isotonic (NaCl 0,9%) vs Hypotonic (Na 0.45%, 0.675% or 0.225%) |
Retrospective cohort Multicentre USA |
472 acutely ill children | Increased risk of hyponatremia in the hypotonic group | Poor quality | Moderate | 2 + |
| Lima et al. (2019) |
PICO 3 Plasma-Lyte A® vs NaCl0.9% |
RCT Single Centre Brazil |
53 acute and critically ill children after brain tumour surgery | Higher chloremia in the NaCl group, and lower natremia in the balanced group | Serious risk | High | 1− |
| Naseem et al. (2020) |
PICO 3 Ringer Lactate vs NaCl 0.9% |
RCT Single Centre India |
70 acutely ill children with dehydration and gastroenteritis | Faster resolution of metabolic acidosis occurs with Ringer lactate | Moderate risk | Moderate | 1− |
| Mahajan et al. (2012) |
PICO 3 Ringer Lactate vs NaCl 0.9% |
RCT Single Centre India |
22 acutely ill children with dehydration and gastroenteritis | No difference | Serious risk | Low | 1− |
| Kartha et al. (2017) |
PICO 3 Ringer Lactate vs NaCl 0.9% |
RCT Single Centre India |
68 acutely ill children with dehydration and gastroenteritis | Clinical and pH improvement increased in the Ringer lactate group | Low risk | Moderate | 1 + |
| Gutman et al. (1969) |
PICO 3 Ringer Lactate vs Cholera designed replacement solution (45 mmol/L acetate) |
RCT Single Centre Taiwan |
27 acutely ill children with dehydration and gastroenteritis (cholera) | Faster normalisation of HCO3 in the cholera buffer enriched solution | Serious risk | Moderate | 1− |
| Farrell et al. (2020) |
PICO 3 Ringer Lactate vs NaCl 0.9% |
Retrospective cohort Multicentre USA |
1581 acutely ill children with pancreatitis | Shorter length of stay and lower costs in the Ringer lactate group | Fair quality | Moderate | 2− |
| Yung et al. (2017) |
PICO 3 Ringer Lactate vs NaCl 0.9% |
RCT Single Centre Australia |
77 acute and critically ill children with moderate and severe diabetic ketoacidosis | No difference | Low risk | Moderate | 1 + + |
| Williams et al. (2020) |
PICO 3 Plama-Lyte A® vs NaCl 0.9% |
RCT Single Centre India |
66 acutely and critically ill children with moderate and severe diabetic ketoacidosis | No difference | Low risk | Moderate | 1 + + |
| Balamuth et al. (2019) |
PICO 3 Ringer Lactate vs NaCl 0.9% |
RCT Single Centre USA |
50 acutely ill children with septic shock | No difference (pilot study) | Serious risk | Low | 1− |
| Bulfon et al. (2019) |
PICO 3 0.9% NaCl, 0,45% NaCl Vs Ringer lactate |
Retrospective cohort Multicentre Canada |
543 critically ill children | Lower risk of Hyperchloremic metabolic acidosis in the ringer lactate group | Good quality | High | 2 + + |
| Martinez Carapeto et al. (2018) |
PICO 4 G3.3% vs G5% MV-MFT |
RCT Single Centre Spain |
130 critically ill children after surgery | No difference | Serious risk | Moderate | 1− |
| De Betue et al. (2012) |
PICO 4 Glucose infusion: 2.5 mg/kg/min vs 5 mg/kg/min |
RCT Single Centre The Netherlands |
11 critically ill children after cardiac surgery | Lower glycemia in the 2.5 mg group, without hypoglycemia | Low risk | High | 1 + |
| Verbruggen et al. (2011) |
PICO 4 Glucose infusion: 2.5 mg/kg/min vs 5 mg/kg/min |
RCT Single Centre The Netherlands |
8 critically ill children after craniosynostosis surgery | Higher hyperglycemia risk in the 5 mg group | Low risk | High | 1 + |
| Lex et al. (2014) |
PICO 4 G10% vs G5% MV-MFT |
Case control study Single Centre Hungary |
596 critically ill children after cardiac surgery | Hospital length of stay was longer in the 10% group | Fair quality | Moderate | 2− |
| Diaz et al. (2018) |
PICO 5 100% (standard) vs 50% (pre-emptive) of Holliday Segar formula |
Case control study Single Centre Chile |
76 critically ill children with sepsis or ARDS | Fluid overload, ventilation duration, length of stay were significantly lower in pre-emptive group | Poor quality | Moderate | 2− |
| Ingelse et al. (2019) |
PICO 5 85% (standard) vs < 70% (conservative) of Holliday Segar formula |
RCT Single Centre The Netherlands |
23 critically ill children respiratory infection on mechanical ventilation | No difference | Critical Risk | High | 1− |
| Yung et al. (2009) |
PICO 5 100% (standard) vs < 2/3 (conservative) of Holliday Segar formula sub studies based on fluid type: A. Normal saline 0.9% B. 4% Dextrose – 0.18% saline |
RCT Single Centre Australia |
50 critically ill children | No difference | Serious risk | Moderate | 1− |
| Raksha et al. (2017) |
PICO 5 0.18% saline in 5%G at 2/3 standard rate vs 0.9% saline in 5%G at standard IV maintenance rate |
RCT Single Centre India |
240 critically ill children |
Less hyponatremia and shorter length of ICU stay in isotonic group No data support the effect of rate/amount due to mixed intervention |
Serious risk | Low | 1− |
| Neville et al. (2010) |
PICO 5 100% (standard) vs < 50% (conservative) of Holliday Segar formula sub studies based on fluid type: A. 5% dextrose + normal saline 0.9% B. 5% dextrose + half normal saline 0.45% |
RCT Single Centre Australia |
62 acutely ill children after surgery | No difference | Serious risk | Moderate | 1− |
| Singhi et al. (1995) |
PICO 5 Standard rate (100% Holliday Segar formula) vs Restrictive rate (65% of standard, liberalization after 24 h with an increase of 10 ml/kg/8 h) Sub studies based on patient status at inclusion: A. Patients without hyponatremia B. Patients with hyponatremia |
RCT Single Centre India |
50 acutely ill children with meningitis | No difference | Serious risk | High | 1− |
EN enteral nutrition; IV intravenous; IV-MFT intravenous maintenance fluid therapy; NPO nil per oral; PO per os; RCT randomised controlled trial