Elevated Intracranial Pressure
Conditions
Keywords
clinical trial, mannitol, intracranial pressure (ICP), hypertonic saline, cerebral edema, traumatic brain injury (TBI)
Brief summary
The study goal is to compare the management of increased intra-cranial pressure (ICP) using 3% hypertonic saline vs. mannitol (given in same osmolar loads). Primary hypothesis: 1\. Hypertonic saline will be non-inferior to mannitol in decreasing elevated ICP. Secondary hypotheses: 1. Hypertonic saline therapy will result with fewer complications than mannitol 2. ICP reduction duration will be longer using hypertonic saline when compared with mannitol
Detailed description
There is growing evidence in the literature indicating that ICP and Cerebral Perfusion Pressure measurements may not be sufficient in the management of elevated ICP. Based on this evidence, monitoring of partial brain tissue oxygenation has gain acceptance among neurosurgeons and neurointensivists, and has become a standard of care monitor in some centers across the country. There is, however, insufficient information in the literature describing the effects of hyperosmolar medications on regional brain tissue oxygenation. We intend to undertake this non-inferiority, prospective, randomized double-blind study to answer very important clinical questions not yet answered in the literature: Will hypertonic saline therapy, given at equiosmolar load, be non-inferior to mannitol in reducing elevated ICP?
Interventions
DRUGhypertonic saline
3% hypertonic saline, dosed by ideal patient weight
DRUGMannitol
Mannitol 20% intravenous solution, dosed by patient's ideal body weight
Sponsors
Beth Israel Deaconess Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * elevated ICP requiring ICP monitoring * ICP ≥ 25 mmHg 5 min after ICP bolt or EVD placement
Exclusion criteria
* Requiring decompressive craniotomy or post decompressive craniotomy * Hyponatremia (sodium level \< 125 mEq/L) * Hypernatremia (sodium \> 155 mmol/L) * Serum osmolality ≤ 250 mOsm/kg * Serum osmolality ≥ 320 mOsm/kg * Physical exam compatible with brain death * Patients on hemodialysis with end-stage renal disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent reduction of ICP from baseline | 30 minutes from completion of medication administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative duration of ICP below 25 mmHg | First 24 hours | — |
| Cumulative duration of cerebral perfusion pressure (CPP) above 60 mmHg | First 24 hours | — |
| Cumulative duration of regional oxygen partial pressure (pbtO2) > 20% | two hours following each dose administration during the first 24 hours | — |
| Total dose of medications given | First 24 hours; also over 3 days | — |
| Time from study drug administration completion to ICP < 25 mmHg | First 72 hours | — |
| Frequency of rebound intracranial hypertension | First 72 hours | Rebound intracranial hypertension defined as ICP \> 25 mmHg for more than 10 minutes following ICP stabilization |
| Frequency of composite Major Adverse Events | 3 days | 1. acute kidney injury as defined by an increase in creatinine x 2 or GFR decrease \> 50% or urine output \< 0.5 ml/kg/h for 12 hours, compared to baseline, as per RIFLE criteria 2. hypotensive episodes (SBP \< 90 mmHg for more than 10 minutes) 3. hemodynamic instability as measured by decrease of cardiac output by more than 15% within two hours following medication administration 4. pulmonary edema as defined by ELWI I\> 10 |
| Difference in inflammatory response | Regular intervals over first 3 days | Determined by analysis of cytokine and inflammatory biomarkers. |
| Difference in average pre-discharge stroke scale score | hospital discharge (or 30 days if not discharged) | — |
| Frequency of treatment failure | First 72 hours | Treatment failure defined as ICP \> 30 mmHg for \> 30 minutes |
Countries
United States
Outcome results
None listed