Acute Liver Failure, Intracranial Hypertension
Conditions
Brief summary
Treatment options in patients with high intracranial pressure due to acute liver failure are limited. This study intends to evaluate the effect of prophylactic hypothermia on preventing high intracranial pressure and compromised cerebral oxidative metabolism.
Detailed description
Acute liver failure (ALF) is associated with a high mortality. With severe hepatic encephalopathy and elevated arterial ammonia concentration (\< 200 micromol/L) more than 50% of the patients will develop high intracranial pressure (ICP) and risk cerebral incarceration and death. The therapeutic options are limited in treating and preventing this condition and new interventions are much sought after. As in hypothermia used for patients after cardiac resuscitation it could be speculated that hypothermia and the reduced cerebral metabolic rate would contribute to neuroprotection and reduce the risk of cerebral hypertension in patients with ALF. We have designed this open, randomized and unblinded study in order to evaluate the effect of prophylactic hypothermia on ICP, cerebral hemodynamics and oxidative metabolism. Patients are randomized to standard medical treatment (SMT) or SMT and hypothermia 33° C for 72 hours using a cooling mattress (Blanketrol II, Cincinnati Sub-Zero). All patients will receive mechanical ventilation, antibiotics, inotropic support and monitored with invasive and non-invasive equipment in accordance to local guidelines. In Copenhagen monitoring cerebral hemodynamics includes: Placement of a intracranial pressure measuring catheter (Camino (R), Integra) for monitoring ICP. Furthermore, a microdialysis catheter (CMA-70) placed in brain cortex is used for monitoring brain metabolism. Finally, cerebral perfusion can be monitored by measuring mean flow velocity using transcranial doppler and/or oxygen saturation in blood from the jugular vein. Ethical considerations: The Helsinki II declaration will be followed and informed consent is mandatory for enrollment. In any patient where hypothermia is believed or suspected to be harmful the study should be stopped and the primary investigator should be notified immediately. All adverse effects will be recorded and published together with the full paper.
Interventions
DEVICEHypothermia by the use of Blanketrol II, Cincinnati Sub-Zero
The patients are placed on a cooling mattress and body-core temperature is regulated to 33° C.
Sponsors
University Hospital Birmingham
Northwestern University Feinberg School of Medicine
Rigshospitalet, Denmark
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* acute liver failure * and hepatic encephalopathy stage 3 or 4 * and informed and written consent by closest relative(s) * and arterial ammonia concentration above 150 micromol/L or clinical suspicion of cerebral edema * and an ICP-measuring device
Exclusion criteria
* no or withdrawn informed consent * pregnant or breast feeding women * uncontrollable infection * hemodynamically instable patients * active bleeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The effect of hypothermia on preventing development of ICP higher than 25 mmHg | 72 hours |
Secondary
| Measure | Time frame |
|---|---|
| The effect of hypothermia on preserving normal cerebral oxidative metabolism evaluated by cerebral microdialysis | 72 hours |
| The effect of hypothermia on severity of infections | 1 week |
Countries
Denmark, United Kingdom, United States
Outcome results
None listed