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The use of hypothermia to 33C within 6 hours of a severe brain injury which is maintained for 48hrs does not improve outcome compared with 'normothermia' of 37C |
Lead author's name and fax: Guy L Clifton, Vivian L Smith Center for
Neurologic Research, University of Texas-Houston Health Science Center, 6431
Fannin, Suite 7.148, Houston, TX 77030;
guy.i.clifton@uth.tmc.edu
Three-part Clinical Question: Does the induction of hypothermia following acute brain injury improve outcome when compared to normothermia?
Search Terms: Acute brain injury, induced hypothermia, outcome, temperature
regulation
The Study:
Single-blinded concealed randomized controlled trial without
intention-to-treat.
The Study Patients: Patients were enrolled in 11 centers in the USA.
Criteria for inclusion were; age 16-65yrs, a non-penetrating head injury, and a
GCS of 3-8 (coma), after resuscitation. Criteria for exclusion were; GCS 3 with
unreactive pupils, a life-threatening injury to an organ other than the brain,
a systolic BP of <90mmHg after resuscitation, oxygen saturation of less than
94% after resuscitation, bleeding, pregnancy, or known pre-existing medical
conditions (e.g. severe heart disease), or if the examiners were unable to
initiate cooling within six hours of the brain injury. ICP was measured in all
patients. All patients received 5-10mg/hr of morphine for at least 72hrs.
Patients who were hypothermic on admission were not actively warmed. CPP was
maintained >70mmHg with fluid or vasopressors. Raised ICP was treated
sequentially with paralysis, ventricular drainage, hyperventilation (limited by
pCO2>30mmHg), mannitol (limited by serum osmo <315mOsm/kg), barbiturate
coma with thiopentone. All patients were loaded and maintained on phenytoin.
Control group (N = 193; 178 analyzed): Constant temperature measurement
via indwelling bladder catheter. Body temperature maintained at 37C. Vecuronium
administered as needed for respiratory management. Enteral or parenteral
feeding commenced within 48hrs of the injury.
Experimental group (N = 199; 190 analyzed): Constant temperature
measurement via indwelling bladder catheter. Cooling began immediately after
randomization; the goal was to achieve the target bladder temperature of 33C
within eight hours of the injury. Cooling procedures included; ice application,
gastric lavage, ventilation with room temperature air. After the target
temperature was achieved temperature control pads were used to maintain the
bladder temperature between 32.5 and 34C for 48hrs. At the end of this period
the patients were rewarmed slowly (<0,5C per 2 hours). All patients in this
group paralyzed with vecuronium for 48hrs to prevent shivering. Enteral or
parenteral feeding commenced 72 hrs after the injury.
The Evidence:
|
Outcome |
Time to Outcome |
CER |
EER |
RRR |
ARR |
NNT |
|
Death |
6 months |
0.249 |
0.266 |
7% |
0.017 |
59 |
|
95% Confidence Intervals: |
42% to 28% |
0.104 to 0.070 |
NNT = 14 to INF; NNH = 10
to INF |
|||
|
Poor Outcome (severe
disability, vegetative state, or death) |
6 Months |
0.528 |
0.543 |
3% |
0.015 |
67 |
|
95% Confidence Intervals: |
22% to 16% |
0.114 to 0.084 |
NNT = 12 to INF; NNH = 9
to INF |
|||
Comments:
A well-conducted multi-center study. Suggests that the routine use of
hypothermia in brain-injured patients is of no benefit, however there are
several additional points. Outcomes in the control group of this study were
better than in a previous study by the same group. The only difference in
management is that in this study control patients who were hypothermic on
admission were not actively warmed. This suggests that either spontaneous
hypothermia is a marker of more severe brain injury or that very early cooling
is necessary to gain a neuro-protective effect. Brain-injured patients who are
hypothermic on admission should NOT be rewarmed.
The results of this study are somewhat surprising when you consider the
theoretical pathophysiological benefits of cooling in brain injury. A possible
reason for this is that the majority of brain-injured patients will develop
pyrexia within the first 48hr following their insult. Pyrexia is an independent
marker of poor outcome. In view of this perhaps the control group in a study of
this kind should not be maintained at 37C as this in not 'normal' and will
require cooling to achieve it in most.
Appraised by: Chris
Cairns, Intensive Care Unit, Western General Hospital, Crewe Road, Edinburgh;
Thursday, January 03, 2002
Email: Chris.Cairns@btinternet.com
Kill or Update By: Jan 2004