2.1. Search strategy and study selection
We registered our review in PROSPERO, and registration ID is
CRD42021225236. We performed a search on PubMed, EMBASE, Cochrane
Library, Web of Science, and ClinicalTrials.gov databases for eligible
studies. We used OpenGrey and National Technical Information Service
databases to search relevant grey literature. The text words or MeSH
were “randomized controlled trail” “intracranial pressure”,
“elevated intracranial pressure”, “hyperosmolar agent”, “hypertonic
saline”, “mannitol” and other synonymous free text words and phrases
were substituted for searching comprehensively. We did not restrict
studies based on language and status of publication. And the published
date was restricted from 2000 to now. We also searched previous
published similar meta-analysis, and screened the included studies. The
search was completed by two investigators independently. And all
disagreements were determined by a third investigator. Then there were
three independent investigators reviewed all references and screened out
eligible studies which conformed to the inclusion and exclusion
criteria. And all disagreements were determined by a fourth
investigator.
2.2. Inclusion criteria :
The included literatures should meet the following items: Patients: (1)
Adult (≥ 16 years old, and of both sexes), (2) episodes of elevated ICP
occurred when used osmotic agents, (3) ICP monitoring (undergoing
quantitative ICP measurement). Interventions: treatments included both
HTS and mannitol. Outcomes: the available quantitative data of ICP.
Study: randomized controlled trails, full text available.
Exclusion criteria :
Studies met the following criteria were excluded: (1) No threshold value
of ICP when osmotic agents were used. (2) Patients with liver or renal
failure, cardiac dysfunction, hypovolemic shock, or multiple organ
failure. (3) Qualitative trials, which had no exact ICP values. (4)
Prehospital studies. (5) Animal studies, retrospective studies, cohort
studies, case report, meta-analysis, and reviews.
Data extraction
To reduce bias, two independent authors extracted data from included
studies. And another author checked the consistencies of the two sets of
data. If there were disagreements, the final decisions were made by
discussion. The basic information included the followings: first
author’s name, publication date, study design, country, sample size,
interventions. Furthermore, the screened clinical outcomes of interest
as followings: (1) ICP, (2) CPP, (3) heart rate (HR), (4) mean arterial
pressure (MAP), (5) serum sodium, (6) serum osmolarity, (7) hematocrit
(HCT). Several interested data were missing, and we had contacted the
corresponding authors to get the information.
Risk of bias
Three authors assessed risk of bias of included studies independently.
Another author solved inconsistencies, if necessary. The Cochrane tool
framework was used to assess risk of bias (9). Mainly included the
following items: (1) random sequence generation (selection); (2)
allocation concealment (selection bias); (3) blinding of participants
and personal (performance bias); (4) blinding of outcomes assessment
(detection bias); (5) incomplete outcome data (attrition bias); (6)
selective reporting (reporting bias); (7) Other bias. For each item, we
assessed the risk of bias as “low risk”, “high risk” or “unclear”.
And we generated a risk of bias summary figure upon completion of these
assessment.
Statistical analysis
Although data in different articles were defined variably, we changed
them in a unified form by the Cochrane Handbook (10). Not every
extracted outcomes could be analyzed meaningfully, we only performed
meta-analyses if outcomes were investigated by at least 3 RCTs. The
continuous variables were pooled using the mean differences (MD) and
95% confidence interval (Cl). The heterogeneity of the studies was
assessed by Q test (P < 0.10 as regards for significant
heterogeneity) and I2 statistic (I2= 0%-25%, no heterogeneity; I2 = 25%-50%, moderate
heterogeneity; I2 = 50%-75%, large heterogeneity;
I2 = 75%-100% extreme heterogeneity) (11). A
random-effect model was applied when I2 >
50%, otherwise fix-effect model was applied. We performed a sensitivity
analysis by excluding each study in turn for outcomes to investigate the
potential source of heterogeneity and effect of each study on pooled
results. And publication bias was estimated by a contour-enhanced funnel
plot and Egger’s test. All data were analyzing by Review Manager 5.3 and
STATA 16.
Characteristics and conclusions of similar systematic reviews
and meta-analyses
We searched and selected similar systematic reviews and meta-analyses on
PubMed, EMBASE, Cochrane Library, Web of Science, and ClinicalTrials.gov
databases. And key information and conclusions were extracted for
further analysis. For methodological quality evaluation, the AMSTAR 2 (A
MeaSurement Tool to Assess systematic Reviews 2) assessment tool was
used. AMSTAR 2 consists of 16 items (7 critical domains: item 2, 4, 7,
9, 11, 13, 15), graded as “Yes,” “Partial Yes,” and “No” (12).
Rating overall confidence in the results of reviews is as follows:
“Critically low”, “Low”, “Moderate” and “High” (12). Three
independent authors evaluated the 16 items and rated all reviews. And
the inconsistencies were discussed by all three authors.
Results