Hypertone Kochsalzlösungen in der Therapie des Schädel-Hirn-Traumas und des traumatisch hämorrhagischen Schocks - Systematische Übersichtsarbeit und Metaanalyse mit Trial Sequential Analysis

Question Hypertonic saline and mannitol are used in intensive care therapy of traumatic brain injury. The superiority of one of the substances has not been demonstrated. The prehospital infusion of hypertonic saline solutions can improve cerebral perfusion in patients with traumatic brain injury and restore circulation and organ perfusion in patients in traumatic hemorrhagic shock. These theoretical benefits have not yet been confirmed in clinical studies. It is unclear whether the infusion of hypertonic saline is superior to current standard therapies. To answer this question, meta-analyses were carried out on the clinical questions "hypertonic saline versus mannitol in traumatic brain injury", "hypertonic saline versus conventional volume therapy in traumatic brain injury" and "hypertonic saline versus conventional volume therapy in traumatic hemorrhagic shock". Methods This study presents meta-analyses of randomized controlled trials on the effectiveness and safety of hypertonic saline solutions versus mannitol or versus conventional volume therapy in the treatment of traumatic brain injury or traumatic hemorrhagic shock. The protocol for the literature searches in the databases Medline, Embase and Central, the quality assessment, the endpoints (mortality, favorable outcome, brain perfusion parameters, hemodynamic, clinical, physiological and laboratory chemical parameters), and the statistical evaluation plan including a trial sequential analysis were prospectively specified and registered on the PROSPERO database. In addition, the results of all meta-analyses including non-randomized controlled trials were presented. Non-controlled studies were also included for the analysis of adverse effects. Results A total of 126 studies with 15,327 patients were eligible for inclusion. In the comparison of hypertonic saline versus mannitol, there was no significant difference in mortality (relative risk [RR], 95 % confidence interval 0.69 [0.45, 1.04]; p = 0.08), despite a nonsignificant trend in favor of hypertonic saline. There were also no significant differences in favorable neurological outcome (RR 1.28 [0.86, 1.90]; p = 0.23). There was no significant difference in intracranial pressure 30–60 min after treatment (mean difference [MD], 95 % confidence interval -0.19 [-0.54, 0.17]; p = 0.30), whereas intracranial pressure was significantly lower after hypertonic saline compared to mannitol at 90–120 min (-2.31 mmHg [-3.17, -1.50]; p < 0.00001). Cerebral perfusion pressure was significantly higher after treatment with hypertonic saline compared with after treatment with mannitol at 30–60 min (MD 5.48 [4.84, 6.12]; p < 0.00001) and 90–120 min (9.08 [7.54, 10.62]; p < 0.00001). There was a nonsignificant tendency in the incidence of treatment failure toward superiority of hypertonic saline (RR 0.71 [0.51, 1.00]; p = 0.05). There was no difference in the duration of daily increased intracranial pressure between the therapy and control group (MD 0.41 [-4.52, 5.34]; p = 0.87). In the comparison of hypertonic saline versus conventional volume therapy in the treatment of traumatic brain injury there was no significant difference in mortality (RR 0.90 [0.78, 1.04]; p = 0.16) or favorable neurological outcome (RR 0.97 [0.86, 1.10]; p = 0.65). There was also no significant difference in the duration of mechanical ventilation (MD 0.02 [-1.25, -1.29]; p = 0.98). Cardiovascular support was significantly shorter in the group treated with hypertonic saline (MD -1.00 [-1.88, -0.12]; p = 0.03). There was no significant difference in systolic blood pressure after 30–60 min or at hospital admission after prehospital therapy (MD -2.04 [-6.43, 2.36]; p = 0.36). In the comparison of hypertonic saline versus conventional volume therapy in the treatment of traumatic hemorrhagic shock, there were no significant differences in long-term mortality (RR 0.94 [0.80, 1.11]; p = 0.47) or 24 h mortality (RR 0.94 [0.75, 1.18]; p = 0.60). The duration of ventilation was not significantly different (MD 0.73 [-0.87, -2.33]; p = 0.37). Cardiovascular support was significantly shorter in the group treated with hypertonic saline (MD -1.00 [-1.88, -0.12]; p = 0.03). Therapy with hypertonic saline led to significantly higher systolic blood pressure after 30–60 min or at hospital admission after prehospital therapy (MD 6.22 [0.73, 11.71]; p = 0.03). There was no significant difference in lactate levels at hospital admission after prehospital therapy (MD -0.25 [-1.14, 0.64]; p = 0.58) or in the incidence of multiple organ failure (RR 0.52 [0.11, 2.51]; p = 0.41). A trial sequential analysis revealed for 4 of the 6 primary outcomes that the data was insufficient to confirm the results with a desired statistical power of 80 %. In the comparisons versus conventional volume therapy, a relative risk reduction of -20 % for a favorable neurological outcome in the therapy of traumatic brain injury and a relative risk reduction of 20 % for long-term mortality in the therapy of traumatic hemorrhagic shock could be excluded with a statistical power of 80 %. Controlled trials on hypertonic saline in trauma patients that were not eligible for inclusion in the meta-analyses were reviewed in a descriptive analysis. Adverse events were uncommon and equally frequent among the treatment groups. Conclusion There are indications that hypertonic saline might be superior to mannitol in intensive care therapy of increased intracranial pressure following traumatic brain injury. Also, hypertonic saline, which was mainly administered prehospitally, showed advantages in clinical and hemodynamic parameters compared to conventional volume therapy. However, there is insufficient data to reach definitive conclusions and further studies are warranted. In particular, advantageous effects could be expected for patients suffering from a combination of traumatic brain injury and hemorrhagic shock.