There are no previous studies that report the rate of IVF treatment in Indonesian community. Studies of the use of IVF are still limited which urge the need of further studies of IVF use in children. The age of the event onset requiring IVFs (Fig. 2) suggested that intravenous fluid use was decreasing starting from 3 months old, before starting to to raise until the peak at 9 months old. In this study, participants who received IVF in the neonatal period were associated with gastrointestinal disorders and infectious diseases (predominantly neonatal sepsis). The major disease occurring at first 2 months of age was respiratory system disorders, while the older ages were predominantly gastrointestinal disorders and respiratory disorders.
IVFs in this study was almost exclusively administered by peripheral IV catheterization. About 55/294 (18.7%) events with IV cathether in this study spent more than 5 days (but less than 15 days. The Michigan Appropriateness Guide for Intravenous Catheters (MAGIC) mentions 7 methods of IVF administration. The most common method, peripheral IV catheterization, is recommended for anticipated IV administration duration of less than 6 days. Beyond that period, other methods such as ultrasonography guided peripheral intravenous catheterization are preferred. (20) Estimating the duration of IV administration, however, is difficult. Ultrasound-guided IV cannulation is more commonly indicated for difficult IV access, such as in obese patients. (21) Absence of other IV catheterization technique (other than peripheral IV catheterization and IO catheterization) in the participants shows the need to explore this topic more, as it might help to improve IV practices in Indonesia.
More than half of total AE indications, based on our study, were given IVF and other concomitant drugs. Peripheral intravenous catheterization is indicated for intravenous (IV) drug administration, IV hydration, transfusion, surgery, emergency care, and in other situations that requires direct IV access. (22) Indications of IV catheterization includes those of IVF, but not vice versa. An article about IV catheterization mention that only 50% of Peripheral IV cannulation (PIVC) were used after installation in the emergency department, and the PIVCs used were intended for fluids only (18.9%), drugs only (40.6%) or both (40.6%). (23) Their finding shows that sometimes PIVC can be used only for IV drugs, without IVFs as well. However, we could not find any article which can recommend whether IVFs should be used together with IV drugs or not, when only IV drugs are needed.
In this study, gastrointestinal disease was the most common indication for IVF administration. In treating diarrhea, intravenous fluid administration is usually indicated for treatment of dehydration (2, 19, 24). Only 4 (4.3%) diarrhea events actually needed IVF because of severe dehydration. However, the rest of 69.9% diarrhea events were not assessable because of unknown hydration status or unknown ability to intake fluid orally. Some diarrhea events recorded no dehydration (25.8%) but were given IVFs, even though there was no identifiable indication for IVF at all. Based on this study, we can only conclude that only 4.3% IVF administration was justifiable in diarrhea events, with at least 25.8% IVF administrations errors.
Among 4 diarrhea events with severe dehydration,only 1 (25%) participant received Plan C rehydration regimen. Among 62 diarrheas with some dehydration, 22 (35.5%) diarrhea events were treated with modified plan B rehydration regimen. The plan B mentioned in this study is a modified WHO plan B rehydration with an addition of IVF infusion, which lacks evidence and has uncertain effectiveness. According to the Indonesian Pediatric Society handbook, IMCI and WHO pocket guide, treatment of diarrhea are categorized into plan A, intended for diarrhea with no dehydration, which require Oral Rehydration Solution (ORS) for ongoing body fluid loss; plan B, intended for some dehydration, which require ORS for fluid replacement and ongoing loss, except for participants with profuse vomiting, who can be treated with IVFs; and plan C, intended for severe dehydration, which require fluid replacement via intravenous or Nasogastric Tube and ORS to replace ongoing loss.(2, 15, 25) This finding shows that only 1 (1%) IVF was used for the right indication and with the right regimen in diarrhea events.
In this study, isotonic fluid was the most used fluid, but a high percentage of hypotonic fluid was still being used. Hypotonic fluids tend to be given to younger participants; this shows that some IVF practices were still based on old theory made by Holliday-Segar. (26) The most frequent IVFs used for maintenance is isotonic fluid, but a large proportion of hypotonic fluids are also used for maintenance fluid. The Indonesian Pediatrics Society's handbook mentioned how much fluid should be administered based on the patient’s weight and they also mentioned to use Dextrose 5% in 0.45% NaCl solution as the fluid of choice for maintenance of Diabetic Ketoacidosis case; however, there is no recommendation of IVF of choice in general. (25) Long standing WHO recommendations stated to use either isotonic or hypotonic IVFs for maintenance IVFs (2) but present studies recommends only isotonic fluids for maintenance (except for neonates) because it is less likely to cause adverse events in children. (1, 19, 24) A study in England (2015), showed that 118 (59%), 63 (32%) and 19 (10%) pediatric patients receive hypotonic, isotonic and hypertonic maintenance respectively. (27) Compared to their finding, maintenance IVF practices in the study showed better adherence to isotonic fluids as maintenance fluid. Even then, we cannot disregard the fact that a large proportion of maintenance fluid in this study were hypotonic fluids.
In our study, 1 case of hyponatremia was detected after a hypotonic fluid administration indicated for pneumonia, on the contrary there is no hyponatremia detected in those who were treated with isotonic fluid. This shows that fluid administration practices can still be optimized to reduce the risk of complications by simply selecting the right choice of fluids.
The most used resuscitation fluid is isotonic fluids, with only a small fraction of hypotonic fluids being used. This finding shows that clinical practice of fluid resuscitation during the duration of the study is good and almost all of clinicians comply to Indonesian Pediatric Society handbook guideline to use isotonic fluid for resuscitation. (25) Recommendations for resuscitative fluids is adamant on using isotonic fluids (1, 2, 19, 24), except perhaps in case of malnutrition. (2) Comparisons of different recommendations for maintenance and resuscitative fluids from different sources are described at Table 8.
Table 8
Comparisons between recommendations of maintenance IVF regimens
Reference | Age | IVF choice | Regimens | Notes |
---|
(2) | < 5 years old | Neonates: First 2 days give D10, afterwards use ½ NS + D5 | Neonates: -day-1: 60 ml/kg/day -day-3: 120 ml/kg/day -day-2: 90 ml/kg/day -then increase to 150 ml/kg/day | -Give more fluid if the neonate is under radiant warmer (1.2–1.5 times).(2) -Every 1°C increase of body temperature should be accompanied by an increase of 10% maintenance fluid needs.(2) -Limit: 2500 ml for boys and 2000 ml for girls.(19) -For term neonates in critical postnatal adaptation phase give minimal to no sodium until postnatal diuresis with weight loss occurs.(19) -If there is a risk of ADH secretion: restrict fluid to 50–80% needs or estimate insensible loss of 300–400 ml/m2 BSA/24 hours plus urine output.(19,24) -Regimen for preterm/low birth weight not shown |
Children: RL + D5, NS + D5 or ½ NS + D5/D10 | For children under 5 years old, a daily rate of: 100 ml/kg for the 1st 10 kg, 50 ml/kg for the 2nd 10 kg, 25 ml/kg after 20 kg |
(1) | 28 days − 18 years old | -For the specified age, use NS + D5 with (if there are no contraindications for potassium) 20 mEq/L KCl | 1500 ml/m2/day or Hourly rate of 4 mL/kg for the first 10 kg, 2 mL/kg for the second 10 kg, then 1 mL/kg after 20 kg. |
(19) | < 16 years old | -Term neonates: isotonic fluid with D5/D10 | Neonates (≤ 28 days old): day-1: 50–60 ml/kg/day day-4: 100–120 ml/kg/day day-2: 70–80 ml/kg/day day-5 till 28: 120–150 ml/kg/day day-3: 80–100 ml/kg/day |
-Children: isotonic crystalloid containing 131–154 mmol/liter of sodium | Children ≥ 29 days until 16 years old, with daily rate of: 100 ml/kg for the first 10 kg, + 50 ml/kg for the second 10 kg, + 20 ml/kg after that |
Hypovolemic shock |
(2) | < 5 years no malnutrition | RL or NS | 20 ml/kg as rapid as possible up to 3 times, then consider epinephrine or dopamine | -If there is hypokalemia, then add 40 mmol/L of Potassium until it reaches normal value, then reduce to 20 mmol/L(24) |
< 5 years old with severe malnutrition | RL + D5/ half strength Darrow's solution + D5/ ½ NS + D5 | 15 ml/kg in 1 hour up to 2 times if there are improvements & no pulmonary edema switch to enteral ReSoMal if there are no improvement give maintenance IVF, transfuse Whole Blood (or PRC if child has cardiac failure) |
(19) | under 16 years old | glucose free isotonic crystalloids containing 131–154 mmol/liter of sodium | children: 20 ml/kg in less than 10 minutes term neonates: 10–20 ml/kg in less than 10 minutes up to 40–60 ml/kg then consult to a specialist |
(24) | - | potassium free 0.9% NS + D5 | 20 ml/kg in less than 10 minutes, up to 3 times, then consider epinephrine or dopamine |
Abbreviations: NS = Normal Saline or 0.9% sodium chloride solution; D5/10 = 5%/10% Dextrose solution; RL = Ringer’s Lactate solution; KCl = potassium chloride. |
Table 8
Comparisons between recommendations of maintenance IVF regiments
Reference | Age | IVF choice | Regiment | Notes |
---|
(2) | < 5 years old | Neonates: First 2 days give D10, afterwards use ½ NS + D5 | Neonates: -day-1: 60 ml/kg/day -day-3: 120 ml/kg/day -day-2: 90 ml/kg/day -then increase to 150 ml/kg/day | -Give more fluid if the neonate is under radiant warmer (1.2–1.5 times).(2) -Every 1°C increase of body temperature should be accompanied by an increase of 10% maintenance fluid needs.(2) -Limit: 2500 ml for boys and 2000 ml for girls.(19) -For term neonates in critical postnatal adaptation phase give minimal to no sodium until postnatal diuresis with weight loss occurs.(19) -If there is a risk of ADH secretion: restrict fluid to 50–80% needs or estimate insensible loss of 300–400 ml/m2 BSA/24 hours plus urine output.(19,24) -Regiment for preterm/low birth weight not shown |
Children: RL + D5, NS + D5 or ½ NS + D5/D10 | For children under 5 years old, a daily rate of: 100 ml/kg for the 1st 10 kg, 50 ml/kg for the 2nd 10 kg, 25 ml/kg after 20 kg |
(1) | 28 days − 18 years old | -For the specified age, use NS + D5 with (if there are no contraindications for potassium) 20 mEq/L KCl | 1500 ml/m2/day or Hourly rate of 4 mL/kg for the first 10 kg, 2 mL/kg for the second 10 kg, then 1 mL/kg after 20 kg. |
(19) | < 16 years old | -Term neonates: isotonic fluid with D5/D10 | Neonates (≤ 28 days old): day-1: 50–60 ml/kg/day day-4: 100–120 ml/kg/day day-2: 70–80 ml/kg/day day-5 till 28: 120–150 ml/kg/day day-3: 80–100 ml/kg/day |
-Children: isotonic crystalloid containing 131–154 mmol/liter of sodium | Children ≥ 29 days until 16 years old, with daily rate of: 100 ml/kg for the first 10 kg, + 50 ml/kg for the second 10 kg, + 20 ml/kg after that |
Hypovolemic shock |
(2) | < 5 years no malnutrition | RL or NS | 20 ml/kg as rapid as possible up to 3 times, then consider epinephrine or dopamine | -If there is hypokalemia, then add 40 mmol/L of Potassium until it reaches normal value, then reduce to 20 mmol/L(24) |
< 5 years old with severe malnutrition | RL + D5/ half strength Darrow's solution + D5/ ½ NS + D5 | 15 ml/kg in 1 hour up to 2 times if there are improvements & no pulmonary edema switch to enteral ReSoMal if there are no improvement give maintenance IVF, transfuse Whole Blood (or PRC if child has cardiac failure) |
(19) | under 16 years old | glucose free isotonic crystalloids containing 131–154 mmol/liter of sodium | children: 20 ml/kg in less than 10 minutes term neonates: 10–20 ml/kg in less than 10 minutes up to 40–60 ml/kg then consult to a specialist |
(24) | - | potassium free 0.9% NS + D5 | 20 ml/kg in less than 10 minutes, up to 3 times, then consider epinephrine or dopamine |
Abbreviations: NS = Normal Saline or 0.9% sodium chloride solution; D5/10 = 5%/10% Dextrose solution; RL = Ringer’s Lactate solution; KCl = potassium chloride |
Isotonic fluids were the mostly used IVF to treat diarrheas, but hypotonic IVFs have been used occasionally for isonatremic diarrheas and might not be the optimal choice. Diarrhea influences body electrolytes and as such, different types of dehydrations might occur, which include hyponatremic, isonatremic and hypernatremic dehydration, which can all be treated with 5% dextrose in 0.9% normal saline. (24) In the only event of hyponatremic diarrhea (1[1.1%] of all diarrhea events), hypertonic saline was administered with Ringer’s Lactate to correct the serum sodium level. Hypertonic saline is recommended in case of symptomatic hyponatremic dehydration but as the participant was assessed with mild hyponatremia, normal saline might prove to be the better option. (24) Some intravenous fluid choice for children with diarrhea used hypotonic fluid as maintenance in this study, which is not optimal and shows that IVF practices have not been in compliance with the latest recommendation.
In this study, blood transfusion was performed in 2 participants with 9.3–9.6 g/dL for pretransfusion hemoglobin (Hb) level and 13.3–14.1 g/dL for posttransfusion Hb level. Latest recommendations state that the more restrictive Hb threshold (7 g/dL) for transfusion reduces blood use and does not result in worse outcome in pediatric intensive care unit. (28) The target Hb concentration recommended is around 8.5–9.5 g/dL. (29) The higher threshold might be justifiable when indicated for the participant with intracranial hemorrhage, because the participant is hemodynamically unstable, but questionable for the participant with cholestasis. Implementation of more restrictive Hb threshold might give more benefit than harm.
Colloid use in this study was Hydroxyethyl starch (HES) and albumin indicated for dengue hemorrhagic fever and cholestasis, respectively. The participant treated with HES was suffering from a fatal dengue shock syndrome. After resuscitation with Ringer’s Lactate, she was given HES, following WHO’s treatment algorithm (30). Albumin is not only intended for volume expansion. In this study it was intended to correct hypoalbuminemia at a concentration of 2 g/dL in a case of cholestasis. Although Indonesian guideline recommended to correct albumin in case of hypoalbuminemia in nephrotic syndrome, there is no recommendation in cholestasis. (25) furthermore, this effort to correct albumin without other primary indication such as hypovolemia or major surgery might be unnecessary. (31, 32)
The study reflects the patterns of IVF administration use in infants and young children in Yogyakarta and Central Java province, and as far as we know, IVFs were administered improperly in the community, and some choice of intravenous fluid used for the participants in this study is not optimal. Practitioners’ knowledge and skills towards intravenous fluid management in children plays a major role in determining the rationality of the treatment, and Mahapatra et al. found that practitioners who live in poor and resource-scarce area have a tendency to be less competent than those who lived in more developed area, which might results in more irrational IVF administration. (33)
Rationality of IVF administration in this study can only be assessed in the way IVF resuscitation were given to participants with diarrhea based on their dehydration level and the result shows more questions rather than answers. Maintenance fluid administration was needed in surgical patients (congenital megacolon, hernia, phimosis, etc.). However, for the rest of those who receive maintenance fluid without accompanying IV drugs and specific indications (e.g. dengue fever and febrile convulsion) which necessitate IVF treatment, its rationale requires further assessment on the patient’s ability to intake fluids orally as stated by the NICE guideline. (6)