Hypothermie thérapeutique en traumatologie crânienne grave

Therapeutic hypothermia (TH) is considered a standard of care in the post-resuscitation phase of cardiac arrest. In experimental models of traumatic brain injury (TBI), TH was found to have neuroprotective properties. However, TH failed to demonstrate beneficial effects on neurological outcome in patients with TBI. The absence of benefits of TH uniformly applied in TBI patients should not question the use of TH as a second-tier therapy to treat elevated intracranial pressure. The management of all the practical aspects of TH is a key factor to avoid side effects and to optimize the potential benefit of TH in the treatment of intracranial hypertension. Induction of TH can be achieved with external surface cooling or with intra-vascular devices. The therapeutic target should be set at a 35 °C using brain temperature as reference, and should be maintained at least during 48 hours and ideally over the entire period of elevated intracranial pressure. The control of the rewarming phase is crucial to avoid temperature overshooting and should not exceed 1 °C/day. Besides its use in the management of intracranial hypertension, therapeutic cooling is also essential to treat hyperthermia in brain-injured patients. In this review, we will discuss the benefit-risk balance and practical aspects of therapeutic temperature management in TBI patients.     

Moderate hypothermia in traumatic brain injury: results of clinical trials

The concept of neuroprotection' by hypothermia dates back to ancient times. This paper reviews the results of clinical trials using mild hypothermia (3235 degrees C) in patients with severe traumatic brain injury over the past decade. Induced hypothermia has been used in experimental models mostly to prevent or attenuate secondary neurological injury and has been used to provide neuroprotection in traumatic brain injury, both in animal models and clinical trials. Results from animal experiments largely confirm that hypothermia can provide protection for the injured brain; however, the results from clinical trials and from a number of meta-analyses have been conflicting. This paper reviews the evidence and explores possible reasons for the mixed results from clinical trials. Hypothermia is clearly effective in controlling intracranial hypertension. Early favourable results on neurological outcome and mortality were not confirmed in a subsequent multi-center trial. Subsequently, single-centre studies, with quicker induction of hypothermia and longer duration of cooling, again reported benefits on outcome. These differences may be explained by differences in study protocols (i.e. speed and duration of cooling, speed of re-warming), prevention of side effects and various supportive measures in the ICU. Although induced hypothermia appears to be a highly promising treatment in various forms of neurological injury including traumatic brain injury, the difficulties in realising its therapeutic potential are underscored by the negative results from a large multi-center trial. Routine usage of hypothermia in traumatic brain injury can not currently be recommended.     

Therapeutic hypothermia for brain injury

Therapeutic hypothermia has an evolving role in the management of patients with brain injury. It is recognized as an integral part of post-resuscitation care following cardiac arrest and its place in managing other forms of brain injury is under ongoing investigation. This article reviews the definitions, proposed mechanisms of benefit, current clinical indications and physiological consequences of mild–moderate therapeutic hypothermia as it relates to brain injury.     

Thrombocytopenia after therapeutic hypothermia in severe traumatic brain injury

Objective: To investigate the clinical characteristics and significance of thrombocytopenia after therapeutic hypothermia in severe traumatic brain injury (TBI). Methods:Ninety-six inpatients with severe brain injury were randomized into three groups: SBC (selective brain cooling) group (n=24), MSH (mild systemic hypothermia ) group (n=30), and control (normothermia) group (n=42). The platelet counts and prognosis were retrospectively analyzed. Results: Thrombocytopenia was present in 18 (75%), 23 (77%) and 15 (36%) patients in SBC group, MSH group and control group, respectively (P<0. 01). Thrombocytopenia, in which the minimum platelet count was seen 3 days after hypothermia, showed no significant difference between SBC and MSH group (P>0.05). Most platelet counts (37 cases, 90 %) in hypothermia group were returned to normal level after 1 to 2 days of natural rewarming. The platelet count in SBC group reduced by 16%, 27% and 29% at day 1, 3 and 5 respectively compared with the baseline value. Good recovery ( GOS score 4-5) rate of thrombocytopenia 1 year after injury for hypothermia group (17 cases, 37%) was significantly lower than that of control group (P < 0.01). Conclusions: Therapeutic hypothermia increases the incidence of thrombocytopenia in severe TBI, and patients with thrombocytopenia after therapeutic hypothermia are associated with unfavorable neurological prognosis.     

Pupillary Abnormality on Admission and Brain Bulging During Surgery as Unfavourable Predictors in Patients Treated with Hypothermia: A Retrospective Review of 81 Patients with Severe Head Injury

Summary. Background: To determine factors predicting outcome of patients with severe head injury, the authors retrospectively analyzed 81 patients, 3 to 70 years of age, who were treated by hypothermia. Method: The initial Glasgow Coma Scale scores of the 81 patients ranged from 3 to 8. Outcome in each case was determined at six months after injury and was retrospectively analyzed with respect to patient characteristics, initial clinical status, laboratory data, computed tomographic findings, data from monitoring, intra-operative findings, and treatment methods. The significance of clinical and neuroradiological factors for predicting unfavorable outcome was analyzed by univariate logistic regression. Stepwise multiple logistic regression analysis was then used to identify independent predictors of outcome. Findings: Favorable outcome was observed in 27 of 81 patients treated by hypothermia. Independent factors predicting unfavorable outcome included pupillary abnormality on admission and brain bulging during surgery. Interpretation: Therapeutic effectiveness of hypothermia was thus limited in patients who presented with these grave symptoms.     

Oxygénothérapie hyperbare et gaz inertes dans l’ischémie cérébrale et le traumatisme crânien

Cerebral ischemia is a common thread of acute cerebral lesions, whether vascular or traumatic origin. Hyperbaric oxygen (HBO) improves tissue oxygenation and may prevent impairment of reversible lesions. In experimental models of cerebral ischemia or traumatic brain injury, HBO has neuroprotective effects which are related to various mechanisms such as modulation of oxidative stress, neuro-inflammation or cerebral and mitochondrial metabolism. However, results of clinical trials failed to prove any neuroprotective effects for cerebral ischemia and remained to be confirmed for traumatic brain injury despite preliminary encouraging results. The addition of inert gases to HBO sessions, especially argon or xenon which show neuroprotective experimental effects, may provide an additional improvement of cerebral lesions. Further multicentric studies with a strict methodology and a better targeted definition are required before drawing definitive conclusions about the efficiency of combined therapy with HBO and inert gases in acute cerebral lesions.     

Hypothermie et protection cérébrale après traumatisme crânien. Influence des gaz du sang

The usefulness of therapeutic hypothermia is highly debated after traumatic brain injury. A neuroprotective effect has been demonstrated only in experimental studies: decrease in cerebral metabolism, restoration of ATP level, better control of cerebral edema and cellular effects. Despite negative multicenter clinical studies, therapeutic hypothermia is still used to a better control of intracranial pressure. However, important issues need to be clarified, particularly the level and duration of hypothermia, the depth and modalities of sedation. A clear understanding of blood gases variations induced by hypothermia is needed to understand the cerebral perfusion and oxygenation changes. It is essential to recognize and to use hypothermia-induced physiological hypocapnia and alkalosis under strict control of cerebral oxygen balance (jugular venous saturation or tissue PO₂) and also to take into account the increased affinity of hemoglobin for oxygen. Management of post-traumatic intracranial hypertension using hypothermia, directed by intracranial pressure level, and consequently for long duration, is potentially beneficial but needs further clarification.     

亚低温治疗重型脑损伤的脑氧代谢和神经电生理临床研究

目的 研究亚低温治疗重型颅脑损伤过程中脑氧代谢和神经电生理变化规律,评估亚低温对重型脑伤的近期疗效。方法 选择受伤后10h内入院GCS（格拉斯哥昏迷评分,Glasgow Coma Scale）3～8分之间的急性重型脑伤患者148例,按病情轻重分为GCS7～8分组、GCS5～6分组和GCS3～4分组,并随机分入亚低温亚组和常温亚组。亚低温亚组（32～34℃）在降温前后的不同时段记录脑氧代谢监测指标、神经电生理指标;常温组在同样的时段记录上述指标。结果GCS7～8分组：SLSEP的N20波幅、BAEP的I／V波幅比值和rSa02在降温后亚低温组较常温组有显著性改善,PbrO2在亚低温组的部分时段低于常温组;GCS5～6分组：亚低温治疗组N20、I／V和rSaO2在部分时段较常温组有改善,PkO2在亚低温组的部分时段高于常温组;GCS3～4分组：亚低温组与常温组上述指标均无显著性差异。结论 亚低温对于GCS7～8分的重型脑伤有明显的治疗作用,对GCS3～4分者无明显疗效,对GCS5～6分者疗效不确定;脑氧代谢和神经电生理指标对颅脑损伤的疗效评价具有重要意义。     

Can we improve neurological outcomes in severe traumatic brain injury?: Something old (early prophylactic hypothermia) and something new (erythropoietin)

Traumatic brain injury is a leading cause of mortality and long-term morbidity, particularly affecting young people. With our best therapies, one half of the patients with severe traumatic brain injury are never capable of living independently. Two interventions, which have real potential to improve neurological outcomes in patients with traumatic brain injury, are (i) very early induction of prophylactic hypothermia and (ii) exogenous erythropoietin therapy. There is substantial experimental evidence, a plausible biological rationale, and supportive clinical evidence from clinical trials to suggest a possible beneficial effect of prophylactic hypothermia and also for exogenous erythropoietin therapy in severe traumatic brain injury. Despite the recent guidelines and publications recommending these interventions, critical care clinicians should be conservative towards implementing these therapies outside clinical trials due to substantial efficacy and safety concerns. Nevertheless the high morbidity and mortality associated with severe traumatic brain injury (TBI) demands that we investigate the safety and efficacy of these promising potential therapies as a matter of urgency.     

Update on Intensive Neuromonitoring for Patients with Traumatic Brain Injury: A Review of the Literature and the Current Situation

Intracranial pressure (ICP) measurements are fundamental in the present protocols for intensive care of patients during the acute stage of severe traumatic brain injury. However, the latest report of a large scale randomized clinical trial indicated no association of ICP monitoring with any significant improvement in neurological outcome in severely head injured patients. Aggressive treatment of patients with therapeutic hypothermia during the acute stage of traumatic brain injury also failed to show any significant beneficial effects on clinical outcome. This lack of significant results in clinical trials has limited the therapeutic strategies available for treatment of severe traumatic brain injury. However, combined application of different types of neuromonitoring, including ICP measurement, may have potential benefits for understanding the pathophysiology of damaged brains. The combination of monitoring techniques is expected to increase the precision of the data and aid in prevention of secondary brain damage, as well as assist in determining appropriate time periods for therapeutic interventions. In this study, we have characterized the techniques used to monitor patients during the acute severe traumatic brain injury stage, in order to establish the beneficial effects on outcome observed in clinical studies conducted in the past and to follow up any valuable clues that point to additional strategies for aggressive management of these patients.     

Hypophosphatemia and hypomagnesemia induced by cooling in patients with severe head injury

OBJECT: Induced hypothermia in patients with severe head injury may prevent additional brain injury and improve outcome. However, this treatment is associated with severe side effects, including life-threatening cardiac tachyarrhythmias. The authors hypothesized that these arrhythmias might be caused by electrolyte disorders and therefore studied the effects of induced hypothermia on urine production and electrolyte levels in patients with severe head injury. METHODS: Urine production, urine electrolyte excretion, and plasma levels of Mg, phosphate, K, Ca, and Na were measured in 41 patients with severe head injury. Twenty-one patients (Group I, study group) were treated using induced hypothermia and pentobarbital administration, and 20 patients (Group 2, controls) were treated with pentobarbital administration alone. In Group 1, Mg levels decreased from 0.98+/-0.15 to 0.58+/-0.13 mmol/L (mean +/- standard deviation; p < 0.01), phosphate levels from 1.09+/-0.19 to 0.51+/-0.18 mmol/L (p < 0.01), Ca levels from 2.13+/-0.25 to 1.94+/-0.14 mmol/L (p < 0.01), and K levels from 4.2+/-0.59 to 3.6+/-0.7 mmol/L (p < 0.01) during the first 6 hours of cooling. Electrolyte levels in the control Group 2 remained unchanged. Electrolyte depletion in Group I occurred despite the fact that moderate and, in some cases, substantial doses of electrolyte supplementation were given to many patients, and supplementation doses were often increased during the cooling period. Average urine production increased during the cooling period, from 219+/-70 to 485+/-209 ml/hour. When the targeted core temperature of 32 micro C was reached, urine production returned to levels that approximated precooling levels (241+/-102 ml/hour). Electrolyte levels rose in response to high-dose supplementation. In the control group, urine production and electrolyte excretion remained unchanged throughout the study period. CONCLUSIONS: Induced hypothermia is associated with severe electrolyte depletion, which is at least partly due to increased urinary excretion through hypothermia-induced polyuria. This may be the mechanism through which induced hypothermia can lead to arrhythmias. When using this promising new treatment in patients with severe head injury, stroke, or postanoxic coma following cardiopulmonary resuscitation, prophylactic electrolyte supplementation should be considered and electrolyte levels should be monitored frequently.     

Study on changes of partial pressure of brain tissue oxygen and brain temperature in acute phase of severe head injury during mild hypothermia therapy

Ahighdeathrateofseverebraininjurieshasattractedmuchattention .Mildhypothermiatherapyandmonitoringbrainoxygenmetabolismandcerebralbloodflowhavebeendoneinmanyhospitals.Wimaretal1elucidatedthevalueofmonitoringbrainoxygeninseverebraininjuries.Butthemechanismofmildhypothermiaremainsunclear .Zhang2 reportedthatmildhypothermiatherapycouldrecoverthebrainoxygentonormal.Gupta3 usedanesthesiacoolingandobservedduringmildhypothermiathebrainoxygenwasdecreased .Wehavetreated 116patientswithseverebraininjuri…     

Hypothermia for brain protection in the non-cardiac arrest patient

This review focuses on the potential application of hypothermia in adults suffering traumatic brain injury (TBI). Hypothermia is neuroprotective, reducing the damaging effects of trauma to the brain in a variety of experimental situations, such as brain ischemia and brain injury, but it has failed to demonstrate outcome improvement in a major controlled, randomized trial. The evidence for the use of hypothermia as a protective procedure is scarce and contradictory. However, evidence does suggest that hypothermia is effective in reducing intracranial hypertension after head injury. Since hypothermia has important side effects, further work is necessary before introducing this procedure into clinical practice for TBI.     

Désordres hydroélectrolytiques des agressions cérébrales : mécanismes et traitements

Electrolyte disturbances are frequent after brain injuries, especially dysnatremia and dyskalemia. In neurological patients, usual clinical signs of hyponatremia are frequently confounded with clinical signs of the underlying disease. Natremia absolute value is less important than speed of onset of the trouble. Most often, hyponatremia is associated with hypotonicity and intracellular hyperhydration, which may exacerbate a cerebral edema. Distinction between inappropriate secretion of antidiuretic hormone (SIADH) and cerebral salt wasting syndrome (CSWS) may be difficult and is mainly based on assessment of patient's volemia, SIADH being associated with normal or hypervolemia and CSWS with hypovolemia. After subarachnoid haemorrhage, the most common disorder is CSWS. In this case, fluid restriction is strictly prohibited. Treatment of CSWS needs to compensate for the natriuresis and may justify the use of mineralocorticoid. It is important to avoid excessively rapid correction of hypernatremia, with a maximal speed of correction of 0.5 mmol/l/h. Serum sodium monitoring should be mandatory for the first ten postoperative days after pituitary adenoma surgery. Therapeutic barbiturate may be responsible for life threatening dyskalemia.     

Le syndrome post-arrêt cardiaque chez l’enfant

The occurrence of post-cardiac arrest syndrome may lead to death in some children who have recovered from a cardiac arrest. The post-cardiac arrest syndrome includes systemic ischaemia/reperfusion response, brain injury, myocardial dysfunction, and persistence of the precipitating pathology. The main cause of death is brain injury. Management includes strictly control of ventilation, oxygen therapy and haemodynamics associated with protection of the brain against any secondary injury: management of seizures, control of glycaemia and central temperature. Mild hypothermia should be considered in comatose children after cardiac arrest.     

Therapeutic hypothermia and acute brain injury

Secondary brain injury has devastating effects on morbidity, mortality and good functional outcomes. Neuroprotection is multimodal, with decades of preclinical and small clinical studies showing the benefits of therapeutic hypothermia. The basic scientific principles have merit, yet large randomized controlled trials fail to show a clear benefit. This article will review the basic science – the practical aspects of delivering targeted temperature management and evaluate the evidence behind its use for acute brain injuries. With a lack of high-quality evidence for hypothermia, recent consensus statements are shifting the paradigm away from hypothermia to the maintenance of normothermia and prevention of pyrexia.     

Recent Advances and Future Directions of Hypothermia Therapy for Traumatic Brain Injury

For severe traumatic brain injury (TBI) patients, no effective treatment method replacing hypothermia therapy has emerged, and hypothermia therapy still plays the major role. To increase its efficacy, first, early introduction is important. Since there are diverse pathologies of severe TBI, it is necessary to appropriately control the temperature in the hypothermia maintenance and rewarming phases by monitoring relative to the pathology. Currently, hypothermia is considered appropriate for severe TBI patients requiring craniotomy for removal of hematoma, while induced normothermia is appropriate for severe TBI patients with diffuse brain injury. Induced normothermia is expected to exhibit a cerebroprotective effect equivalent to hypothermia, as well as reduce the complexity of whole-body management and systemic complications. According to the Japan Neurotrauma Data Bank of the Japan Society of Neurotraumatology, the brain temperature was controlled in 43.9% of severe TBI patients (induced normothermia: 32.2%, hypothermia: 11.7%) in Japan. Brain temperature management was performed mainly in young patients, and the outcome on discharge was favorable in patients who received brain temperature management. Particularly, patients who need craniotomy for removal of hematoma were a good indication of therapeutic hypothermia. Improvement of therapeutic outcomes with widespread temperature management in TBI patients is expected.     

What works in severe head injury?

Traumatic brain injury has an important socioeconomic impact in industrialized countries. However, well-conducted clinical trials are rare. Case-control studies have shown that prevention works. Pathophysiological understanding is becoming more complete as data on chemokines, local brain tissue oxygen tension and hypothermia accumulate. Multimodality monitoring will certainly assume greater importance in the future. Research with targeted therapeutic strategies indicates that secondary ischaemic insults can be prevented. Specific subgroups of patients with traumatic brain injury who will benefit from the use of hypothermia and barbiturates have been identified. Enteral feeding is the preferred nutritional strategy, and the follow-up period should be extended beyond the traditional 1 year.     

Clinical analysis of hypothermia in children with severe head injury

Therapeutic hypothermia may improve outcome after severe head injury, but its efficacy has not been established in children with a severe head injury. The authors evaluated the effects of hypothemia (33-34 degrees C) in 9 severely closed head-injured children (under 16 years old). The cooling period was 3 to 21 days (mean 9.3). Hypothermia significantly reduced ICP when it reached 33-34 degrees C. From 3 to 6 months after injury, 6 (67%) of the 9 patients had good outcome (good recovery in 2 and moderate disability in 4), but 3 (33%) had poor outcome (severe disability in 2 and vegetative state in one). Complications, including infectious disorders (pneumonia, meningitis, sepsis), cardio-vascular system dysfunction (cardiac arrhythmia, hypotension), decreased platelet counts, hypokalemia, diabetes insipidus, acute pancreatitis occurred during hypothermia in 7 patients (78%). The results of this study suggest that treatment with hypothermia in children with severe head injury is often accompanied complications, but it is an effective method to control intracranial hypertension and may have improved the outcome.     

Hypothermia in adult neurocritical patients: a very 'hot' strategy not to be hibernated yet!

Therapeutic moderate hypothermia (32-34 degrees C) is currently recommended for patients with out-of-hospital cardiac arrest (OHCA) and for newborns exhibiting neonatal hypoxic/ischemic encephalopathy. Hypothermia as neuroprotective strategy has been extensively studied in other scenarios, mainly for traumatic brain injury. Despite a negative result reported by a multicenter trial conducted in 2001 by Clifton et al. regarding the use of hypothermia on head injury patients, several studies in both clinical and laboratory settings have continued to report positive outcomes with hypothermia use in neurocritical care. To date, no adequate consensus has been reached. Though the topic is still under debate, emerging data suggest that there may not be a clear-cut answer as to whether hypothermia is beneficial. However, new research may indicate what target populations can benefit most from this therapy. Furthermore, issues of timing (when and for how long hypothermia is applied) seem to be the primary drivers of the most unambiguous findings in this matter. For the time being, we conclude that further studies are needed to assess how to better administer this possibly beneficial therapy, and who might benefit most from the technique.