In total, 1554 records were found and screened, 43 were extracted after title screening. Among which, 36 articles were excluded because of intervention or article types. And only 7 studies4, 13, 14, 20-23 were included in the qualitative and quantitative synthesis (Figure 1). A total of 4520 patients were included in the seven studies. However, 962 patients in IJVC group and 180 patients in SCVC group were dropped out, because ultrasound guidance was taken since the first attempt. Finally, 1783 and 1595 patients were analyzed in each group. For studies that included more than just IJVC and SCVC4, 13, 22, 23, we extracted data only related to IJVC and SCVC. The details of the included studies are summarized in Table 3.
Primary Outcomes
Catheterization time
Only two studies13, 14 recorded the catheterization time that was not their original established outcome, though, the meta-analysis showed no difference in catheterization time between IJVC and SCVC (SMD 95% CI: -0.095-0.124, p=0.792. Figure 2). The operators and the patients in the two studies significantly varied (Table 3) that were complicated doctors (experienced and non-experienced) to adults13 and experienced doctors to children (<6 y)14. Low heterogeneity (I2=0.0%) was detected; however, the clinical heterogeneity could’ve played a key role in this comparison. The inconsistent and limited studies we retrieved precluded us from any meaningful conclusion between the two procedures. More high-quality randomized clinical trials focusing on the catheterization time would be essential to clarify this issue.
Overall success rate
Five studies 4, 13, 14, 20, 22compared the overall success rate were included in the quantitative analysis. No significance was detected in meta-analysis (RR=1.017, 95% CI: 0.927-1.117, p=0.721, Figure 2.). This primary outcome was characterized by significant heterogeneity (I2=89.6%). Subgroup analysis based on age (18y) was performed. The subgroup analysis showed that the overall success rate of IJVC was significantly lower than that of SCVC (RR=0.906, 95%CI:0.850-0.965, p=0.002, Figure 3) in adult patient group. It’s noteworthy that all catheterizations were finally achieved in a small sample size (n=45) study21 and it was excluded from the quantitative analysis. However, the pediatric patients group still posed high heterogeneity (I2=91.2%), two studies favored the IJVC for higher success rate20, 22 while the other two favored SCVC4, 14.
Secondary Outcomes
First-attempt success rate
Only two studies14, 21 contributed to this secondary outcome, however, the heterogeneity was significant (I2=78.4%). Operated both by experienced doctors, the main differences lie in the age of patients and the catheter lumen (Table 3), for patients under 6 years old14, SCVC tended to achieve higher first-attempt success rate (Figure 3); while for adults21, IJVC had a significant higher first-attempt success rate that was contrary to the overall success rate (Figure 3).
Arterial injury
All the included studies recorded arterial injury complication, probably because it’s one of the most common instant mechanical complications both in traditional landmark cannulation and the ultrasound assisted cannulation2, 24. The seven studies together created a moderate heterogeneity (I2=70.2%), but no significant statistical difference was detected between the two insertion sites in the quantitative analysis (RR=1.137, 95% CI: 0.541-2.387, p=0.735, Figure 2).
Pneumothorax
Pneumothorax was evaluated in four studies4, 13, 14, 22. The incidence of pneumothorax in IJVC group wasn’t significantly different with that of SCVC group (RR=0.600, 95% CI: 0.32-1.126, p=0.112, I2=0.0%, Figure 2). Notably, three studies4, 13, 22 had a tendency indicating a lower incidence rate of pneumothorax in IJVC group.
Hematoma
The same four studies that evaluated pneumothorax also evaluated hematoma. Hematoma was significantly more in IJVC group than that in SCVC group (RR=2.824, 95% CI: 1.181-6.751, p=0.02, I2=4.8%, Figure 2).
Subgroup analyses
We conducted subgroup analyses to investigate the influence of patients’ age on all outcomes. For the catheterization time, neither adult patients were detected of any statistical difference between the two procedures (SMD=-0.005, 95%CI: -0.123-0.113, p=0.929), nor were any statistical difference in pediatric patients (SMD=0.141, 95%CI: -0.145-0.437, p=0.349). Since this result was only recorded but not pre-designated as their outcome in the original two studies, as one of our primary outcomes, it seemed embarrassing. For overall success rate, the subgroup analysis by age has shown a significant lower overall success rate in IJVC group than that in SCVC group in adult patients (RR=0.906, 95%CI:0.850-0.965, p=0.002, Figure 3), however, high heterogeneity was shown in pediatric patients (I2=91.2%) and no significant difference was detected (RR=1.056, 95%CI:0.931-1.198, p=0.395, Figure 3).
The first-attempt success rate, when analyzed in subgroups, IJVC group achieved a higher first-attempt success rate than SCVC group in the adult patients (RR=1.472, 95%CI:1.004-2.156, p=0.047, Figure 3), whereas in the pediatric patients, no significant difference was detected (RR=0.931, 95%CI:0.788-1.100, p=0.399, Figure 3). The subgroup analyses of arterial injury didn’t detect any statistical differences neither in adult patient group (RR=2.767, 95%CI:0.729-10.511, p=0.135, Figure 3) nor in pediatric patient group (RR=0.940, 95%CI:0.406-2.177, p=0.149, Figure 3) between the two procedures. Likewise, the subgroup analyses of pneumothorax incidents didn’t find any statistical differences in different age groups between the two CVC ways (Figure 3). The hematoma incidence rate, however, when analyzed by age subgroups, IJVC showed significant higher rate than SCVC in adult patient group (RR=7.235, 95%CI:1.534-33.919, p=0.012, Figure 3), whereas in the pediatric patients, IJVC posed a higher risk trend but no significance was found (RR=1.870, 95%CI:0.689-5.077, p=0.219, Figure 3).
Sensitivity analyses
We conducted sensitivity analyses with a fixed effects model alternatively. The outcome of the catheterization time and first-attempt success rate were also performed regardless of small number of studies. The results of sensitivity analyses were largely consistent with the primary analysis. (supplemental data)
Publication bias
The funnel plots for the outcomes of overall success rate, arterial injury, pneumothorax and hematoma were conducted. Publication bias on the catheterization time and first-attempt success were not calculated because of limited studies included. Since the number of included studies for any outcome is small, the funnel plot could have limited power to detect the bias. (supplemental data)