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An Experimental Model of Diet-Induced Metabolic Syndrome in Rabbit: Methodological Considerations, Development, and Assessment
Published on: April 20, 2018
Maintaining normal intracranial pressure in a rabbit model during treatment of severe diabetic ketoacidemia
G D Harris1, I Fiordalisi, C Yu
1Department of Pediatrics, East Carolina University School of Medicine, Greenville, North Carolina 27858, USA.
Insights
Controlled fluid management during diabetic ketoacidemia (DKA) treatment can prevent dangerous intracranial pressure (ICP) increases in pediatric patients. This study shows managing effective osmolality (Eosm) is key to minimizing ICP rise in DKA treatment.
Area of Science:
- Pediatric Endocrinology
- Neurology
- Critical Care Medicine
Background:
- Diabetic ketoacidemia (DKA) management in children can lead to increased intracranial pressure (ICP), causing severe neurologic complications or death.
- Previous studies indicate that correcting hyperglycemia and treating DKA can paradoxically elevate ICP.
- The role of effective osmolality (Eosm) changes during DKA treatment in ICP elevation is not fully understood.
Purpose of the Study:
- To investigate the hypothesis that controlled changes in effective osmolality (Eosm) can minimize ICP elevations during DKA treatment.
- To compare ICP changes in DKA rabbits treated with standard fluid resuscitation versus a modified fluid regimen.
Main Methods:
- Three groups of rabbits were studied: normal controls (Cnor), DKA controls (CDKA) receiving standard fluid replacement, and DKA experimental (EDKA) receiving half the calculated fluid deficit.
- All DKA groups received insulin for hyperglycemia correction.
- ICP, Eosm, and other physiological parameters were monitored throughout the six-hour study period.
Main Results:
- The CDKA group showed a progressive and significant increase in ICP during treatment.
- The EDKA group exhibited no significant increase in ICP compared to normal controls.
- Changes in Eosm were significantly greater in CDKA compared to both Cnor and EDKA, while EDKA's Eosm changes were not significant compared to Cnor.
Conclusions:
- Decreasing effective osmolality (Eosm) during DKA treatment is strongly associated with increased ICP.
- DKA can be effectively treated with intravenous fluids and insulin while preventing ICP elevation by carefully controlling fluid administration and Eosm changes.
- This approach offers a safer management strategy for pediatric DKA patients at risk for intracranial hypertension.
Abstract:
Increased intracranial pressure (ICP) resulting in death or neurologic morbidity continues to complicate traditional management of diabetic ketoacidemia (DKA) in pediatric patients. When ICP or cerebrospinal fluid pressures have been measured, correction of hyperglycemia in animals and treatment of DKA in humans have consistently resulted in pathologic increases in ICP. We hypothesized that elevations in ICP can be minimized if changes in effective osmolality (Eosm) are controlled during treatment of DKA. During a six-hour study period, three groups of rabbits were studied: a normal control group of nondiabetic animals (Cnor, n = 10), a control group of animals with DKA (CDKA, n = 8), and an experimental group of animals with DKA (EDKA, n = 8). There was no significant difference between the two groups with DKA regarding pretreatment degree of dehydration, blood pressure, hyperglycemia, acidemia or ICP. During the treatment period, Cnor received maintenance fluids only. CDKA received insulin and an assumed volume of deficit (150 ml/kg) along with maintenance fluids and urinary output replacement with 0.45% NaCl. EDKA received insulin and one-half the volume of deficit calculated by the weight lost with 0.9% NaCl plus maintenance fluids. There was no significant difference between CDKA and EDKA regarding the rate at which DKA was corrected. While CDKA demonstrated a progressive and statistically significant increase in ICP, EDKA exhibited no such increase in ICP compared to normal, nondiabetic controls (Cnor) during treatment. Changes in Eosm during treatment in CDKA compared to Cnor and in CDKA compared to EDKA were significantly greater (p < .01), however, changes in EOSM in EDKA compared to Cnor were not significant. These data support the clinical observation that decreasing EOSM during treatment of DKA is associated with increased ICP and suggest that DKA can be treated effectively with i.v. fluids and insulin without increasing ICP.
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