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Rehydration Therapy: SubQ May Be the Thing to Do

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altPediatric dehydration continues to be a significant cause of morbidity and mortality throughout the world and is a frequent issue encountered in the Emergency Department.   Traditionally, IV fluid hydration has been the mainstay of therapy.   However, it is often difficult to obtain intravenous (IV) access in children who have small, collapsed veins, and therefore, alternative therapies are being investigated. 

Educational Objectives: After evaluating this article, participants will be able to:
1. Identify the different forms of pediatric rehydration and incorporate them into clinical practice.
2. Implement strategies to apply the different strategies to the appropriate clinical situations.
3. Implement a subcutaneous rehydration program

 

Pediatric dehydration continues to be a significant cause of morbidity and mortality throughout the world and is a frequent issue encountered in the Emergency Department.   Traditionally, IV fluid hydration has been the mainstay of therapy.   However, it is often difficult to obtain intravenous (IV) access in children who have small, collapsed veins, and therefore, alternative therapies are being investigated.  Oral rehydration works well but many providers feel that this process is too time-consuming.  Subcutaneous rehydration therapy (SCRT), known as “hypodermoclysis,” is emerging as a potential alternative to IV fluid administration in patients with mild-to-moderate dehydration. The use of a recombinant human hyaluronidase enzyme at the infusion site can increase the rate of fluid administration by up to five times. Unlike animal-derived forms of hyaluronidase, the recombinant human form has a lower chance of allergic reactions with repeated dosing. The SQ route may be beneficial in patients who have failed oral rehydration therapy or have difficult IV access. This article will discuss rehydration therapy including oral rehydration, nasogastric hydration and subcutaneous rehydration.

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Q. Does oral rehydration really work and what are the risks/benefits?

A. Oral rehydration is extremely effective and this Cochrane review confirmed that patients who can feed orally are typically discharged faster than those who received IV therapy. However, as expected, there are more treatment failures with ORT and a higher incidence of paralytic ileus than in patients who receive IV therapy. The bottom line:  For every 25 children treated with ORT, one would fail and require IVT.

Citation: Hartling L, Bellemare S, Wiebe N et al. Oral versus intravenous rehydration for treating dehydration due to gastroenteritis in children. Cochrane Database Syst Rev. 2006 Jul 19;3:CD004390.

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Summary: The Cochrane Infectious Diseases Group Specialized Register (March 2006), CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE (1966 to March 2006), EMBASE (1974 to March 2006), LILACS (1982 to March 2006), and reference lists were searched.  Also sources from researchers, pharmaceutical companies, and relevant organizations were reviewed for additional information. Randomized and quasi-randomized controlled trials comparing intravenous rehydration therapy (IVT) with oral rehydration therapy (ORT) in children up to 18 years of age with acute gastroenteritis were reviewed.

Methods: Two authors independently extracted data and assessed quality using the Jadad score.  Dichotomous data was expressed as a risk difference (RD) and number needed to treat (NNT), and continuous data as a weighted mean difference (WMD).

Results: Seventeen trials (1811 participants), of poor to moderate quality, were included. There were more treatment failures with ORT (RD 4%, 95% confidence interval (CI) 1 to 7, random-effects model; 1811 participants, 18 trials; NNT = 25). Six deaths occurred in the IVT group and two in the ORT groups (4 trials). There were no significant differences in weight gain (369 participants, 6 trials), hyponatremia (248 participants, 2 trials), hypernatremia (1062 participants, 10 trials), duration of diarrhea (960 participants, 8 trials), or total fluid intake at six hours (985 participants, 8 trials) and 24 hours (835 participants, 7 trials). Shorter hospital stays were reported for the ORT group (WMD -1.20 days, 95% CI -2.38 to -0.02 days; 526 participants, 6 trials). Phlebitis occurred more often in the IVT group (NNT NNH?) 50, 95% CI 25 to 100) and paralytic ileus more often in the ORT group (NNT (NNH? Need to ask Ghazala about these two) 33, 95% CI 20 to 100, fixed-effect model), but there was no significant difference between ORT using the low osmolarity solutions recommended by the World Health Organization and IVT (729 participants, 6 trials). Although no clinically important differences between ORT and IVT were identified, the ORT group did have a higher risk of paralytic ileus, and the IVT group was exposed to risks of intravenous therapy. For every 25 children (95% CI 14 to 100) treated with ORT one would fail and require IVT.

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Q. Does nasogastric hydration work in children with dehydration?

A. Nasogastric hydration works extremely well and is particularly useful in children with difficult intravenous access. This study revealed that patients actually had an increased rise in their bicarbonate and had fewer urinary ketones than patients who underwent IV hydration.

Citation: Nager AL, Wang VJ. Comparison of nasogastric and intravenous methods of rehydration in pediatric patients with acute dehydration. Pediatrics. 2002 Apr;109(4):566-72.

Objective: To assess the safety, efficacy, and cost-effectiveness of rapid nasogastric hydration (RNG) and rapid intravenous hydration (RIV) administered in the emergency department (ED) to young children suffering with uncomplicated, acute moderate dehydration.

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Methods: Ninety-six children aged 3 to 36 months, who presented with signs and symptoms of uncomplicated, acute moderate dehydration caused by vomiting and/or diarrhea, presumed to be caused by viral gastroenteritis, were randomly assigned to receive either RNG with a standard oral rehydration solution or RIV with normal saline. Each solution was administered at a rate of 50 mL/kg of body weight, delivered over a 3-hour period in our urban pediatric ED. All participants were weighed pretreatment and post-treatment and underwent initial and final measurements of their serum electrolytes, blood urea nitrogen, creatinine, and glucose levels, along with urine chemistry and urine specific gravity. Telephone follow-up by completion of a standardized questionnaire was obtained approximately 24 hours after discharge from the ED.

Results: Ninety-two of 96 enrolled patients completed the study. Three patients failed treatment (2 RIV and 1 RNG) and were excluded and hospitalized because of severe, intractable vomiting, and 1 patient was withdrawn secondary to an intussusception. Among 92 evaluable patients, 2 were found to be severely dehydrated (>10% change in body weight) and were excluded from analysis, leaving 90 patients (RNG: N = 46 and RIV: N = 44), who completed the study. Both RNG and RIV were found to be a safe and efficacious means of treating uncomplicated, acute moderate dehydration in the ED. Determinations of electrolytes, blood urea nitrogen, creatinine, or glucose were not found to be of value on an intent-to-treat basis in the care of these patients. The urine specific gravity and incidence of ketonuria declined from levels commensurate with moderate dehydration in the RNG group, but not as consistently in the RIV group.
Both RNG and RIV were substantially less expensive to administer than standard care with intravenous fluid deficit therapy via hospital admission, and RNG was more cost-effective to administer over RIV in the outpatient setting.

Conclusion: RNG and RIV administered in the ED are safe, efficacious, and cost-effective treatment options for uncomplicated, acute moderate dehydration in young children. RNG is as efficacious as RIV, is no more labor intensive than RIV, and is associated with fewer complications. In addition, we found that most routine laboratory testing is of little value in these patients and should be avoided, except when clearly clinically indicated

Q. Does recombinant human hyaluronidase-enabled subcutaneous hydration work in children?

A. While recombinant human hyaluronidase (rHuPH20)-facilitated subcutaneous rehydration is a promising new method, larger studies are necessary before routine use can be advocated.

Citation_1: Allen CH, Etzwiler LS, Miller MK,etal. Recombinant human hyaluronidase-enabled subcutaneous pediatric rehydration. Pediatrics. 2009 Nov;124(5):e858-67. Epub 2009 Oct 5.

Objective: The Increased Flow Utilizing Subcutaneously-Enabled (INFUSE)-Pediatric Rehydration Study was designed to assess efficacy, safety, and clinical utility of recombinant human hyaluronidase (rHuPH20)-facilitated subcutaneous rehydration in children 2 months to 10 years of age.

Methods: Patients with mild/moderate dehydration requiring parenteral treatment in US Emergency Departments were eligible for this phase IV, multicenter, single-arm study. They received subcutaneous injection of 1 mL rHuPH20 (150 U), followed by subcutaneous infusion of 20 mL/kg isotonic fluid over the first hour. Subcutaneous rehydration was continued as needed for up to 72 hours. Rehydration was deemed successful if the patient’s improvement, was attributed by the investigator,  to be primarily due to subcutaneous fluid infusion, and the child was discharged without requiring an alternative method of rehydration.

Results: Efficacy was evaluated in 51 patients (mean age: 1.9 years; mean weight: 11.2 kg). Initial subcutaneous catheter placement was achieved with 1 attempt for 46/51 (90.2%) of patients and the remainder were successful on the second attempt.   Rehydration was successful for 43/51 (84.3%) of patients. Five patients (9.8%) were hospitalized but still rehydrated primarily through subcutaneous therapy, for a total of 48/51 (94.1%) of patients. Investigators found the procedure easy to perform for 96% of patients (49/51 patients), and 90% of parents (43/48 parents) were satisfied or very satisfied. The median time to begin infusion from initiation of catheter placement was 2 minutes. Eighty-eight percent of the parents reported that they would choose this method in the future should their child require rehydration. Three children required a second dose of hyaluronidase in order to maintain the infusion. The median flow rate was 19 mL/hour, and the average total volume delivered was 418 mL. Six patients (12%) required slowing of the infusion rate due to infusion site issues, and 1 patient (2%) was withdrawn from the study due to infusion site pain. One serious adverse event occurred and involved cellulitis in a child who was hydrated for 45 hours via the subcutaneous route.

Conclusions: rHuPH20-facilitated subcutaneous hydration seems to be safe and effective for young children with mild/moderate dehydration. Subcutaneous access is achieved easily, and the procedure is well accepted by clinicians and parents.

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Citation_2: Rouhani S, Meloney L, Ahn R, Nelson BD, Burke TF. Alternative rehydration methods: a systematic review and lessons for resource-limited care. Pediatrics. 2011 Mar;127(3):e748-57. Epub 2011 Feb 14.

Objective: Dehydration is a significant threat to the health of children worldwide and a major cause of death in resource-scarce settings. Although multiple studies have revealed that oral and intravenous (IV) methods for rehydration in non-severe dehydration are nearly equally effective, little is known about effectiveness beyond these 2 techniques. With this systematic review, the effectiveness of non-oral and non-intravenous methods of rehydration were evaluated.

Methods: The Medline, Cochrane, Global Health, Embase, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases were searched for articles on intraosseous (IO), nasogastric (NG), intraperitoneal (IP), subcutaneous (hypodermoclysis), and rectal (proctoclysis) rehydration through December 2009 were reviewed. Only human pediatric studies that included data on the effectiveness or complications of these methods were included.

Results: The search identified 38 articles that met the inclusion criteria: 12 articles on NG, 16 on IO, 7 on IP, 3 on subcutaneous, and none on rectal rehydration. NG rehydration was as effective as IV rehydration for moderate-to-severe dehydration. IO rehydration was effective and easy to obtain, although only 1 randomized trial was identified. IP rehydration had some benefit for moderate dehydration, although none of the trials had control groups. Limited data were available on subcutaneous rehydration, and only 1 case series showed benefit.

Conclusions: NG rehydration should be considered second-line therapy, after oral rehydration, particularly in resource-limited environments. IO rehydration seems to be an effective alternative when IV access is not readily obtainable. Additional evidence is needed before IP and subcutaneous rehydration can be endorsed.

Final Analysis:
While subcutaneous hydration is emerging as a new therapy for dehydration and NG hydration has been shown to be effective, the use of oral rehydration is markedly underutilized by emergency providers.  It is strongly recommended by the AAP and with the use of ondansetron, ORT can be extremely beneficial  in dehydrated children. It can save a child from undergoing multiple needlesticks for IV placement and is preferred by the parents. The key to success is involving the parents and letting them know that while it is a slow process at first, patients improve more rapidly when the GI tract is involved as shown by Nager’s study on NG hydration.  If the patient requires IV hydration, here are some easy tricks:

Easy Pediatric Fluids

Here’s a quick and simple way to manage dehydration in a child.

Step 1.  Estimate the degree of dehydration using all of the tools in you armamentarium – tears, tongue, turgor, level of activity, history, etc.  It is by no means an exact science – and doesn’t have to be – just choose mild, moderate or severe.
 
Step 2. If mild or moderate, give oral rehydration therapy with some Pedialyte or Rehydralyte or similar fluids.  The amount for mild dehydration is about 50ml/kg and 100ml/kg for moderate.  Give small amounts frequently with the goal to rehydrate in about 4 hours.  Consider some ondansetron if there is vomiting.
 
Step 3.  If severe dehydration, give 150ml/kg of normal saline. Boluses of 20ml/kg should  be given if aggressive treatment is needed. Check a blood sugar and replace with either D10 in newborns or D25 in children
 
Step 4.  Add to the rehydration fluids the child’s maintenance fluids that would be required for 4-6 hours.  For the first 10kg of a child’s weight it is 4cc/kg/hour; for the second 10kg of weight it is about 2ml/kg/hour and for every kg thereafter it is an additional 1ml/kg.   So a 22 Kg child would receive: 40ml + 20ml+ 2ml= 62ml/hour of maintenance fluid

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