Clinical Outcomes of Hypertonic Saline vs Mannitol Treatment Among Children with Traumatic Brain Injury

Shu-Ling Chong, M.D. Yanan Zhu, PhD. et al.

2025년 3월 11일

JAMA Netw Open 2025; 8(3):e250438

DOI: 10.1001/jamanetworkopen.2025.0438

Abstract

Importance

The use of hypertonic saline (HTS) vs mannitol in the control of elevated intracranial pressure (ICP) secondary to neurotrauma is debated.

Objective

To compare mortality and functional outcomes of treatment with 3% HTS vs 20% mannitol among children with moderate to severe traumatic brain injury (TBI) at risk of elevated ICP.

Design, Setting, and Participants

This prospective, multicenter cohort study was conducted between June 1, 2018, and December 31, 2022, at 28 participating pediatric intensive care units in the Pediatric Acute and Critical Care Medicine in Asia Network (PACCMAN) and the Red Colaborativa Pediátrica de Latinoamérica (LARed) in Asia, Latin America, and Europe. The study included children (aged < 18 years) with moderate to severe TBI (Glasgow Coma Scale [GCS] score ≤ 13).

Exposure

Treatment with 3% HTS compared with 20% mannitol.

Main Outcomes and Measures

Multiple log-binomial regression analysis was performed for mortality, and multiple linear regression analysis was performed for discharge Pediatric Cerebral Performance Category (PCPC) scores and 3-month Glasgow Outcome Scale–Extended Pediatric Version (GOS-E-Peds) scores. Inverse probability of treatment weighting was also performed using the propensity score method to control for baseline imbalance between groups.

Results

This study included 445 children with a median age of 5.0 (IQR, 2.0-11.0) years. More than half of the patients (279 [62.7%]) were boys, and 344 (77.3%) had severe TBI. Overall, 184 children (41.3%) received 3% HTS, 82 (18.4%) received 20% mannitol, 69 (15.5%) received both agents, and 110 (24.7%) received neither agent. The mortality rate was 7.1% (13 of 184 patients) in the HTS group and 11.0% (9 of 82 patients) in the mannitol group (P = .34). After adjusting for age, sex, presence of child abuse, time between injury and hospital arrival, lowest GCS score in the first 24 hours, and presence of extradural hemorrhage, no between-group differences in mortality, hospital discharge PCPC scores, or 3-month GOS-E-Peds scores were observed.

Conclusions and Relevance

In this cohort study of children with moderate to severe TBI, the use of HTS was not associated with increased survival or improved functional outcomes compared with mannitol. Future large multicenter randomized clinical trials are required to validate these findings.

Key Points

Question  Among children with moderate to severe traumatic brain injury, is the use of 3% hypertonic saline (HTS) associated with better survival and functional outcomes compared with 20% mannitol?

Findings  This cohort study included 445 children treated with 3% HTS, 20% mannitol, both agents, or neither agent. No between-group differences in mortality, discharge Pediatric Cerebral Performance Category Scale scores, or 3-month Glasgow Outcome Scale–Extended Pediatric Version outcomes were observed.

Meaning  These findings suggest that compared with mannitol, HTS was not associated with increased survival or improved functional outcomes.

요약

·         소개 : 이 연구는 중등도에서 중증의 외상성 뇌손상을 입은 소아 환자에서 3% 고장성 식염수(HTS)와 20% 만니톨 치료의 사망률 및 기능적 결과를 비교하기 위한 전향적 다기관 코호트 연구이다

·         방법 : 본 연구는 2018년 6월 1일부터 2022년 12월 31일까지 아시아, 라틴 아메리카, 유럽의 28개 소아 중환자실에서 진행되었으며, 연구 대상은 글래스고 혼수 척도(GCS) 점수 13 이하의 중등도에서 중증 외상성 뇌손상을 입은 18세 미만의 소아 445명이었다. 이 중 184명(41.3%)은 3% 고장성 식염수 치료를, 82명(18.4%)은 20% 만니톨 치료를 받았다.

·         결과 : 사망률은 HTS 그룹7.1%, 만니톨 그룹 11.0%로 나타났으나, 통계적으로 유의한 차이는 없었다(P = .34). 또한 퇴원 시 PCPC 점수와 3개월 후 GOS-E-Peds 점수에서도 두 그룹 간 유의한 차이가 없었다.

결론 및 의의: 중등도에서 중증의 외상성 뇌손상을 입은 소아 환자에서 3% 고장성 식염수 사용은 20% 만니톨과 비교하여 생존율이나 기능적 회복에 유의한 이점을 보이지 않았다.