Abstract
Aims : Currently, mannitol and hypertonic saline (HTS) are mostly used in treatment of adult with elevated intracranial pressure (ICP). However, there is no high-level evidence on the superiority of mannitol versus HTS. Therefore, a systematic review and meta-analysis was performed to compare effects of hypertonic saline and mannitol for treatment of adults with elevated ICP.
Methods : We performed a search on lots of databases for eligible studies. Prospective randomized control trials comparing HTS and mannitol in adults with elevated ICP were included, and ICP monitoring should be applied. Primary outcome was change of ICP values, and secondary outcomes were changes of cerebral perfusion pressure (CPP), mean arterial pressure (MAP), heart rate, serum sodium, serum osmolarity and hematocrit (HCT).
Results: A total of ten studies (384 patients, 1578 episodes) were included. A pooled result indicated HTS reduced ICP more effectively than mannitol. At 0.5 h, 1 h, and 2 h after intervention, results also showed a better efficiency of HTS than mannitol. In addition, results indicated elevation of CPP, serum sodium and serum osmolarity were all more in HTS group than in mannitol group. And there were no statistical significance in changes of MAP, HCT and HR between the two interventions.
Conclusion: Our study indicated HTS had a better efficiency in reduction of elevated ICP than mannitol in earlier stage. Based on the current level of evidence of ICP control and effects in other physiological indicators, HTS could be recommended as a first-line agent for managing patients with elevated ICP.
Key words: intracranial pressure, mannitol, hypertonic saline, meta-analysis, systematic review.
Introduction
Acutely elevated intracranial pressure (ICP) is a life-threatening neurosurgical emergency situation, which is a frequent manifestation of several brain injury in case of traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), stroke (hemorrhagic and ischemic), infection, and neoplasm. The secondary brain injury associated with elevated ICP can lead to impaired cerebral perfusion pressure (CPP) and poor neurological outcome and mortality (1). And the normalization of ICP in patients with brain injury is assumed to limit secondary brain injury and improve outcome. In conditions of elevated ICP, hyperosmolar agent is used as the most common treatment. And mannitol and hypertonic saline (HTS) are usually employed for reduction of elevated ICP in clinical treatment. Mannitol is a typical medicine, which plays an important role in treatment of elevated ICP for about 60 years. For recent years, HTS (concentrations ranging from 3% to 30%) has been emerging as a good substitute for mannitol. Several studies suggested that HTS was better than mannitol in controlling elevated ICP (2, 3). However, some other studies reported that there was no difference between HTS and mannitol in reduction of ICP (4-7). Moreover, the “Guidelines for the Management of Severe Traumatic Brain Injury (Fourth Edition)” stated “although hyperosmolar therapy may lower intracranial pressure, there was insufficient evidence about effects on clinical outcomes to support a specific recommendation, or to support use of any specific hyperosmolar agent” (8).
Although there were some similar published systematic reviews and meta-analyses, the methodological quality and the conclusions were not satisfactory and rigorous. Up to now, there is no high-level evidence on the superiority of mannitol versus HTS in reducing ICP or improving outcomes. After searching electric databases, we found several high quality and eligible trials. Consequently, we combined their findings in a new meta-analysis to explore a more precise conclusion. In present article, we analyzed and summarized previous meta-analyses. Then, by searching electric databases and screening numerous articles, the eligible trials and quantitative data were extracted. Finally, a systematic review and meta-analysis was performed to compare the effects of HTS and mannitol in treatment of adults with elevated ICP. Furthermore, we expect present conclusions would give several valuable strategies for clinical treatment.
Methods