The national guideline from 2002 says adults should not have a femoral central line because of the risk of CRBSI. But there is no scientific evidence to back that up. As a result of CDC/HICPAC and international guidelines [45, 46], the Institute for Healthcare Improvement recommended following "a central line bundle" for preventing catheter related blood stream infections [19, 46,47,48,49]. Subsequently, several studies examined whether or not site selection affected infectious risk while strictly following central line bundles. The recommendation encourages early removal as well as careful drapement and daily examination of all lines to ensure their necessity. In the years since central line bundles have been introduced, numerous studies have been conducted, but no correlation has been found between insertion site preference and infection risk [26, 28, 29]. In this study, we examined the research question: do catheter-related bloodstream infections differ much between non-tunneled jugular and femoral access? In what ways could inverse probability treatment weighting be used to draw conclusions from observational [50, 51] data? There have only been a few studies in the pediatric population that look at the same thing, as far as we know. We present a novel approach to investigating this question by comparing femoral and internal jugular lines to standard care, as well as compliance with the central line bundle, using inverse probability treatment weighting to balance covariates [18, 22, 52,53,54,55].
In fact, when estimating treatment effects from longitudinal observational studies, balancing weights are becoming more popular because people are not randomized [56,57,58,59]. A combination of probability score matching and inverse probability treatment weighting was used to balance the weights between groups (femoral versus internal jugular). Through balancing weights, we can create pseudo-randomized studies [60, 61] because we create comparable treatment groups based on key pretreatment characteristics that could have confounded treatment effect estimates. A causal diagram [43] was developed before we built a propensity score-based weighting model, so we could account for backdoor paths from covariates. Based on the causal diagram, site selection and bloodstream infection must be accounted for attributing causal impact to weight and age. On the other hand, TPN variables, PICU length of stay, central line days, how frequently a line was opened, and whether or not the patient was immunocompromised, have no effect on the causal pathway.
According to our study, the sample's median age was 12 months (IQR 4 to 72). It is lower than many other published data points [62,63,64], and men dominate, as they do in most research papers [64]. Furthermore, the CRBSI rate is noteworthy because it's higher than a few [62, 65] but lower than the majority of the research articles [63, 64, 66,67,68] In addition, we observed a CRBSI rate of 4.10 for 1463 central line days, but we predicted 1.902 for the same days. Therefore, our risk-adjusted standardized infection ratio was 3.155 [69, 70], compared with 1.3 for the National Healthcare Safety Network (NHSN) and the Centers for Disease Control and Prevention (CDC) [71]. The CDC defined 1 as the National Benchmark as of December 2010. In other words, a hospital with a CRBSI score of 1 does well since it means the score is the same as similar-sized or shaped hospitals [70,71,72]. Honestly, six CRBSI events in 13 months seems good to me. The CRBSI rate was not good enough when compared to a benchmark for the study period.
We included 96 internal jugular lines (control) and 49 femoral lines (treatment) with six covariates in the final matching model (Fig. 1). On the basis of the unmatched data, the mean age of the treated group was 64.93 months, and 33.61 months for the control group, resulting in a SMD of about 0.593. In fact, there was an imbalance in all covariates (SMD > 0.1), except for the length of stay in the PICU (SMD = 0.037) (Table 1). Interestingly, all covariates in both groups after post-matching ranged from 0.01 to 0.04 for standardized mean differences. (Table 1) Therefore, for casual inference estimation, this is a perfect balance for a 1:1 match between 49 femoral and 49 internal jugular lines. (Figs. 2, 3, 4).
The causal relative risk of CRBSI was estimated from the weighted data as 4.67, CI (0.872–25.05), P = 0.09 (Table 2). In other words, femoral lines are 4.67 times more likely to have CRBSI than internal jugular, but the difference is not statistically significant. Contrary to Goetz's (2016) published article with conflicting results, where she observed a CRBSI hazard ratio of 4.2; CI (2.0–8.8); P-value of 0.0001 [73]. There has been a similar finding in another author's work [74]. But Kumar (2009) reported catheter-related bloodstream infections were similar in femoral and internal jugular lines (2.3 vs 1.5 per 1000 catheter-days, respectively; P = 0.42). The jugular and femoral access sites are equally likely to cause catheter colonization, catheter-related bloodstream infection, and thrombosis in critically ill adult intensive care unit patients. This is contrary to the widely held belief that infections are more common at femoral access sites in adults. It does not make sense to extrapolate this to pediatric ICU patients because the recruited sample only includes adult patients on renal replacement therapy [31]. In addition, a systematic review showed that catheter-related bloodstream infections did not differ significantly between femoral and internal jugular sites. In this publication, the risk ratio was 1.35, with a 95% confidence interval of 0.84–2.19 and a P value of 0.2 [75]. Similarly, from December 2011 to June 2014, 3SITES, a randomized, controlled study involving four hospitals to the jugular group, the femoral group had an identical risk of CRBSI (hazard ratio, 1.3; 95% CI, 0.8 to 2.1; P = 0.31) [26]. While early studies suggested that femoral site access was associated with a higher risk of infection in adults, this has not been confirmed. As of this writing, research has shown no significant difference in the rate of CRBSI between these centers, assuming compliance with the central line bundles is maintained [76].
It is worth noting that the research discussed above focuses primarily on adult populations. There have been few articles in pediatrics that deal with this topic. The first study in King Abdulaziz Medical City, Riyadh, has been published. The researchers looked at catheter-related blood stream infection for catheters inserted in the PICU compared to operating rooms, and for catheters inserted in the femoral versus jugular or subclavian site (P*0.001) using a multiple logistic regression analysis [51]. Another interesting point is that 4512 CVC patients were enrolled in the second study. There was no evidence that any one of the sites had an increased risk of infection compared with the other sites, with hazard ratios of 0.951 (95% confidence interval [CI] 0.612–1.478) for the subclavian site, 0.956 (95% CI 0.593–1.541) for the internal jugular site, and 1.120 (95% CI 0.753–1.665) for the femoral site. Cox regression was used to adjust for age, severity of illness, and number of catheter days [50]. Recently, a prospective cohort study entitled "Central Venous Catheter Types and the Risk of Bloodstream Infection I n the Pediatric Intensive Care Unit: Two Years' Experience" was published in September 2021. A multiple logistic regression was used to capture the effects of preexisting compounding factors. Nevertheless, the results did not contradict our findings. OR 1.04, CI (0.49–3.49). Interestingly, the author included a central line bundle in the care process. In contrast to our study, Topal et al. (2021) had a larger sample size [77], but the median age and weight were similar to our patients' while infection rates were higher, at 6.2/1000 catheter days [78]. To learn more, Derderian et al. (2019) found that femoral lines had no significant risk factors for CRBSI in contrast to internal jugular lines, but they did show an association with venous thromboembolism [79]. Last but not least, Silvetti et al. (September 2017) enrolled an RCT on ClinicalTrials.gov that hypothesized that catheter colonization and CRBSI are less likely in the jugular insertion site than in the femoral insertion site in pediatric cardiac surgery [80]. The final results remain to be seen. We are looking forward to following this up in order to gain a deeper understanding of the experience.
Here, we looked at causality instead of associations. In addition, we have chosen to primarily focus on children as our sample population. To the best of our knowledge, an inverse probability treatment weighting based on propensity scores has never been reported previously for casually inferring CRBSI from non-tunneled femoral versus internal jugular vascular access. Furthermore, we used a standardized regression model to estimate the actual and counterfactual probability of CRBSI in femoral lines, which is another new approach. The factual probability of CRBSI was 4.14%, CI (0.09–7.49%), and the counterfactual probability was 2.79% (− 0.062%, 6.19%) (Table 2). The number of CRBSI during the observed period would not change if no femoral lines were inserted during the ICU stay or if the femoral line location was avoided. In combination with the standardized regression and the risk ratios from the weighted generalized multiple regression model, we found a risk difference of 0.074, CI (− 0.019, 0.169), P = 0.06, which supports our finding that there is no difference in CRBSI risk between non-tunneled femoral and internal jugular vascular access (Table 2). For instance, all the author used logistic regression to overcome the bias. Propensity-based weighting beats logistic regression on these fronts. It showed that the bias diminished as the number of events per confounder increased. In logistic regression, bias control depends entirely on the number of events and covariates. As an alternative, propensity score-based weighting could eliminate bias independent of events and covariates [81]. Finally, we believe another strength of our study is that our causality as a whole is not affected by unobserved covariates. We measured the Wilcoxon Signed Rank P-Value based on the Rosenbaum Sensitivity test [82], which estimates the hidden bias and explains the impact it has on our results. In spite of the high gamma levels, no unobserved confounding factors have been identified by the P-values in our study. Therefore, we were right to claim causality.
Implications
There has been a gap in the research regarding CRBSI rates between femoral and internal jugular vascular access in pediatric intensive care. This study offers a new perspective for looking at this issue with an appropriate study design: a multicenter, double-blind, randomized control trial. Additionally, this is the first, a method used for estimating propensity score-based matching with inverse probability treatment weighting for causal inference, has been applied in a study. Furthermore, the article evaluates the attributable risk of bloodstream infections associated with the femoral central line, which is a unique approach in our article, and the beneficial effects of the central line bundle for preventing CRBSI, which have been further emphasized. In sum, our findings and the results of a few previous studies suggest that a central line associated with bloodstream infection placed in the femoral line is no more at risk than one placed in the jugular. Based on our results and findings of prior studies, we conclude that if the central line bundle is strictly maintained, there is no additional risk of bloodstream infection for the femoral line when compared to the internal jugular. It will be interesting to see how the enrolled RCT performs in this regard. We are very eager to pursue this opportunity to further our understanding and to have a rewarding experience.
Some limitations were encountered in this study. To begin with, we only collected data at one site, especially with few observations over short periods of time. Having a multicenter cohort is definitely superior to having a single-center, but our point estimate has a risk ratio similar to those that have been published in other studies. Second, since the study is an observational study, the causal inference does not have the same level of meaning as a randomized controlled trial (RCT), which is considered the gold standard in clinical research. Noteworthy, our treat and control groups balance metric SMD -values ranging 0.01to 0.04 after propensity score matching and weighting, which is only possible in a randomized clinical trial. Thus, we were correct in asserting causation. Moreover, the Rosenbaum Sensitivity Test for Wilcoxon Signed Rank P-Value for unobserved cofounding estimation and cause-and-effect diagrams indicate that our research provides strong evidence for true causality. The third point is that we cannot comment on several potentially important infection control practices that applied to both the femoral and internal jugular, including the length of the lines, the frequency with which each central line was open, and the same-level skilled provider inserting the lines. However, for both kinds of lines, we could guarantee equal maintenance of the central line bundle. Finally, we suggest a multicenter, double-blind randomized control trial to gain even further insights into the issue because the observational study, in addition to the small sample size, might not be sufficient to detect a meaningful difference.
