Fever episodes occur in more than 50%of patients with subarachnoidal hemorrhage despite antibiotic and antipyretic therapy.The exact mechanism of hyperthermia-induced brain injury is not known. Hyperthermia might increase the release of excitatory neurotransmitters or trigger an amount of oxygen free radicals. Hyperthermia may also aggravate blood-brain barrier disruption.The deleterious effect of fever has been demonstrated in patients with subarachnoidal hemorrhage. MedDRA version: 9.1 Level:
Conditions
Interventions
Trade Name: Dantrolen
Product Name: Dantrolen
Product Code: 17.709
Pharmaceutical Form: Injection*
Pharmaceutical form of the placebo: Intravenous infusion
Route of administration of the placebo: Intr
Sponsors
Medizin Universität Wien
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The study will be restricted to neurosurgical patients after subarachnoidal hemorrhage aged from 18 to 80 years. There will be no limitation of enrollment as to patients breathing spontaneously or being ventilator dependant. AND sustained fever (=38ºC for more than an hour) without an identifiable infectious cause. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Patients who, in the judgment of the attending anesthesiologist, have active infection likely to cause fever. The judgment will be based on the following evidence collected within 24 hours of study enrollment: white blood cell count above 12,000 c/dL, opacities in chest x-rays, sputum containing pus from visual exam, or positive cultures of sputum, blood, or urine. • Pregnancy determined by giving a urine pregnancy test immediately before consent is obtained. Female patients less than 50 years of age will undergo a pregnancy test unless there is a history of previous hysterectomy. • Patients who have been diagnosed with arrhythmia within 24 hours of study enrollment • Patients with a history of muscular dystrophy • Patients in whom the dose of mannitol for treatment or placebo groups is contraindicated by having increased serum osmolarity (> 320 mOsmol/L) as measured immediately following signature of informed consent. Hypotension will not be an issue because all neuro intensive care patients are kept at least normotensive using fluid or vasopressors if indicated. • Patients who are known to have acute liver disease at the time of study enrollment as shown by the most recent lab tests available within 72 hours of screening. If appropriate tests are not available , they will be performed after informed consent is obtained. The tests are as follows: ALT> 94 u/L, AST > 120 u/L. • Patients who have stage 2 cirrhosis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: We test the hypothesis that dantolen will reduce centrally mediated fever in patients after subarachnoidal hemorrhage. Specifically we will test the hypothesis that dantrolene decreases the magnitude and duration of hyperthermia.;Secondary Objective: ;Primary end point(s): As soon as fever = 38°C is detected, a series of cultures and laboratory samples will be taken per Neuro Intensive Care Unit routine for febrile patients. Immediately after drawing the culture samples, fever will be treated according to the ICU protocol: administration of 1000 mg paracetamol per nasogastric tube or orally with a 20-ml flush of free water. If fever does not decline by 0.5°C after 30 minutes patients will be randomly assigned to the dantrolene group or to the placebo group (see below). If in the judgment of the anesthesiologist attending the febrile episode is due to an infection, specific antibiotic treatment will be initialized by the anesthesiologist and the study will be stopped, the subject will be considered withdrawn, and the data will not be used. After antibiotic treatment, if another fever episode occurs without any clinical association to infection, the patient will be reevaluated for inclusion/exclusion criteria and if criteria are met the patient will be re-enrolled using a different randomization number. Patients who satisfy the inclusion/exclusion criteria of the study and who are enrolled in this study will be randomized with computer-generated grouping to either one of two groups. One group of subjects will be given dantrolene for the first episode of fever The other group will be given placebo. Dantrolene is supplied in 70-ml vials containing 20 mg dantrolene and 3000 mg mannitol, reconstituted with 60 ml of sterile water. Dantrolene will be given in the following dose: 5 mg/kg given intravenously over 30 minutes containing 750 mg/kg mannitol. As placebo mannitol will be used, as 20mg dantrolene contains 3000mg mannitol. The placebo will be given | — |
Countries
Austria
Outcome results
None listed