Hypertonic Saline vs. Mannitol in Pediatric Diabetic Ketoacidosis with Cerebral Edema
Date First Published:
May 25, 2007
Last Updated:
June 18, 2007
Report by:
Josh Vander Lugt, MD, Emergency Medicine Resident (Michigan State University/GRMERC)
Search checked by:
Jeff Jones, MD, Michigan State University/GRMERC
Three-Part Question:
In [pediatric patients with diabetic ketoacidosis and evidence of cerebral edema] is [intravenous mannitol or hypertonic saline] better [in reducing neurologic disability or mortality]?
Clinical Scenario:
In treating pediatric patients with diabetic ketoacidosis (DKA), minimizing the risk of cerebral edema is a mainstay of therapy. However, the pathophysiologic mechanism of cerebral edema in pediatric DKA is controversial. A literature search is performed to assess the evidence favoring the use of mannitol vs. hypertonic saline in the treatment of pediatric DKA.
Search Strategy:
Medline 1950-05/07 using the OVID interface, Cochrane Library (2007), PubMed clinical queries.
[(exp diabetic ketoacidosis/) AND (exp brain edema or cerbral edema.mp or cerebral oedema.mp/). LIMIT to human AND English AND all child
[(exp diabetic ketoacidosis/) AND (exp brain edema or cerbral edema.mp or cerebral oedema.mp/). LIMIT to human AND English AND all child
Search Details:
PubMed: cerebral edema or oedema and hypertonic saline and mannitol and pediatric diabetic ketoacidosis
OVID: cerebral edema or oedema and hypertonic saline and mannitol and pediatric diabetic ketoacidosis
OVID: cerebral edema or oedema and hypertonic saline and mannitol and pediatric diabetic ketoacidosis
Outcome:
129 papers were found; 10 papers addressed therapy in cerebral edema.The majority of these were small case reports or case series. None of the studies compared mannitol to hypertonic saline in pediatric DKA. One retrospective study was identified that examined outcomes in children treated with mannitol (1) and one study addressed the issue of hypertonic saline in pediatric cerebral edema, though it was not strictly limited to children with DKA (2).
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| Hypertonic saline treatment in children with cerebral edema. Yildizdas D, Altunbasak S, Celik U, et al September, 2006 Turkey | 67 pediatric intensive care unit patients with cerebral edema of varying etiologies, including meningoencephalitis, hypoxic ischemic encephalopathy, intracranial hemorrhage, meningitis, or metabolic encephalopathy. | Group I: Received only mannitol Group II: Recieved only hypertonic saline Group III: Received both mannitol and hypertonic saline. This group is subdivided into IIIA and IIIB. In Group IIIB, patients with serum osmolality greater than 325 mosmol/L had mannitol discontinued, and were treated with hypertonic saline alone. |
Mortality and duration of comatose state | Hypertonic saline more effective than mannitol in the treatment of cerebral edema | Small, retrospective study. Only 7/67 patients fit into the "metabolic encephalopathy" group, which would correlate best with patients in DKA. Outcomes were "duration of comatose state" and "mortality". No mention of long-term disability. |
| Factors associated with adverse outcomes in children with diabetic ketoacidosis-related cerebral edema. Marcin, James P. MD, MPH; Glaser, Nicole MD; Barnett, Peter MB, BS; McCaslin, Ian MD; Nelson, David MD; Trainor, Jennifer MD; Louie, Jeffrey MD; Kaufman, Francine MD; Quayle, Kimberly MD; Roback, Mark December, 2002 USA | Children <= 18 years old with DKA and cerebral edema were retrospectively identified from 10 pediatric centers between 1982 and 1997. | Studied relation between outcomes of children with diabetic ketoacidosis(DKA)-related cerebral edema and clinical outcome in association with therapeutic interventions for treatment of cerebral edema. Worse outcomes associated with dehydration, more profound neurologic depression at diagnosis of cerebral edema, and hyperventilation. | Effect of mannitol use on adverse neurologic sequelae | Not able to prove or disprove the harm or efficacy of mannitol. | Retrospective, small. Non-standardized dosing of mannitol. Non-standardized timing of therapeutic implementation for patients treated. Assessment of patient neurologic status subject to interobserver variability. Study limited in its ability to evaluate use of mannitol specifically. |
Author Commentary:
Performing a large and high-quality study to compare mannitol vs. hypertonic saline in the setting of pediatric DKA poses numerous ethical and logistical difficulties. At this time, most of the literature regarding hypertonic saline and mannitol in cerebral edema is related to patients with traumatic brain injury. More investigation is needed before definitive recommendations can be made. Marcin, et al. showed a compelling relationship between poor neurologic outcome and hyperventilation, dehydration, and worse neurologic status at time of cerebral edema diagnosis. Although Yildizdas, et al. report the advantage of hypertonic saline over mannitol in cerebral edema in general, translating these results specifically to cerebral edema in pediatric DKA would be premature.
Bottom Line:
Mannitol does not appear to worsen outcomes in pediatric patients with DKA and evidence of cerebral edema. Currently, no good evidence supports the use of hypertonic saline over mannitol in this specific group of patients.
References:
- Yildizdas D, Altunbasak S, Celik U, et al. Hypertonic saline treatment in children with cerebral edema.
- Marcin, James P. MD, MPH; Glaser, Nicole MD; Barnett, Peter MB, BS; McCaslin, Ian MD; Nelson, David MD; Trainor, Jennifer MD; Louie, Jeffrey MD; Kaufman, Francine MD; Quayle, Kimberly MD; Roback, Mark. Factors associated with adverse outcomes in children with diabetic ketoacidosis-related cerebral edema.