Peripheral Vasopressors—Are We Avoiding the Central Issue Altogether?*

A central venous catheter (CVC) has long been the gold standard route for vasoactive use, but the need for timely initiation of such agents, and challenges with CVC placement, has prompted peripheral venous access (PVA) for vasoactives. In this issue of Pediatric Critical Care Medicine, two articles add to our collective knowledge on the topic of such PVA in children. Both of these reports include around 200 children, some of the largest to date. Safety of PVA remains the primary question, one of these articles (Levy et al [1]) pushes further to address the clinical scenarios where placement of a CVC might be avoided altogether. Timely initiation of vasoactives being a central element of the Surviving Sepsis Guidelines for Children (2) and they include explicit acknowledgment that peripheral use may be necessary. While the panel did not make a specific recommendation regarding PVA, they recommend that central access be pursued “as soon as reasonably practicable” and report that 18% of their panel members do not use vasoactives peripherally (2). More and more, however, we are working to minimize duration of CVCs, as maintenance bundles and other quality improvement strategies have decreased but not completely eliminated the risk of central line-associated bloodstream infections (CLABSIs) (3).

In a single-center retrospective cohort spanning 6 years, Levy et al (1) describe 231 children supported with PVA. Compared with the group who had central administration of vasoactives, the PVA group were older, presented with a lower illness severity by Pediatric Risk of Mortality-III score and were more likely to be admitted in the nighttime. They were less likely to be supported by mechanical ventilation, and so it stands to reason that their PICU stays were also shorter. There is likely to also be a predisposition to earlier CVC placement in a patient already on mechanical ventilation, both because sedation proves easier than in the unintubated patient, as the authors discuss (1), and the likely need for multiple access points in the intubated patient. In terms of adverse events (AEs), they were primarily extravasations from the peripheral vein, which were identified in 1.7% of PVA cases. Complications related to CVC placement were not reported. The cohort included 93 patients with a diagnosis of septic shock (40%), of whom 47% never had a CVC placed. The median time to placement of a CVC in PVA cases was 140 minutes, indicating that the decision was often made in a matter of a few hours. Patients with a lower illness severity more often avoided central line placement. These results indicate that there is a population of shock patients who can be supported with peripheral access alone. It begs the question of how long to wait before deciding to proceed with a CVC attempt.

Also, in this issue of Pediatric Critical Care Medicine, Peshimam et al (4) present a retrospective observational cohort of pediatric patients transported by pediatric critical care transport teams in the United Kingdom, a total of 558 transports where vasoactive agents were used, 35.5% (198) via peripheral access. The primary AE was extravasation, which occurred in 3.5% of PVA cases. Remarkably, when comparing transport times between patients with PVA and those who had a CVC placed on transport, the transport duration was only increased by a median of 10 minutes. The duration of the infusion of vasoactive agents in the PVA group was 180 minutes in the patients who did not have an extravasation noted (interquartile range, 105–320 min). The PVA group was more likely to have a diagnosis of bronchiolitis (17.7% vs 3.8%) or lower respiratory tract infection (LRTI) (19.7% vs 12.5%) than the CVC or intraosseous group. They did not report the proportion of patients who ultimately required the placement of a CVC, although 9 (4.5%) were still receiving PVA at 24 hours after PICU admission.

Although the authors of the study Peshimam et al (4) argue that the rate of AEs in the PVA group was not different than the rate of 2.5% in the combined CVC and intraosseous group, this is likely due to the effect of a high rate of intraosseous complications (11.6%) rather than the CVC group (1.3%). Separating the intraosseous group in the analysis potentially would have shown a difference between the AEs in the PVA and CVC groups. However, the AEs measured occurred on transportation or within 24 hours, so were limited to immediately recognizable vascular injuries (extravasation in PVA, extraosseous infusion in intraosseous, and mechanical issues in CVCs). While counted as equal in this analysis, dilation of the femoral artery is likely to be a more significant injury to the patient than a peripheral venous extravasation, although one of the seven extravasations in the PVA group did require surgery (4).

The rate of extravasation of a vasoactive agent out of a peripheral vein were similar in these two articles (Levy et al [1] and Peshimam et al [4]), although higher (3.5% vs 1.7%) in the transport cohort. It stands to reason that a peripheral catheter would have a higher risk of dislodgement on transport than while in the PICU. These rates are both comparable to the pooled rate (3.5%) of AEs in a recent meta-analysis of peripheral vasoactive use in four pediatric studies (388 subjects) (5). Notably, a prior pediatric transport study of 73 subjects with PVA reported that 17% of subjects experienced extravasation, occurring at a mean of 7 hours after PICU arrival. A more recent report of 45 children with multisystem inflammatory disorder in children (MIS-C) related to COVID-19 who received PVA over a 7-month period identified only one extravasation in an adolescent patient at hour 21 of infusion. Both studies in this issue present the event rate of AEs associated with each of the routes in the initial period, however, we are likely missing a big component of the overall risk of CVCs. Aside from the risks of sedation or anesthesia for placement, immediate complications like large vessel injury and hemorrhage, longer-term risks of CVCs, accumulating each day, has been on the mind of critical care practitioners.

The overall rate of CLABSI remains at 1.39 per 1,000 catheter days in a report of 176 U.S. hospitals from 2013 to 2018 (3). This rate was stable throughout the study period and reflects sustained improvement from efforts improving line insertion and maintenance bundles, but the authors assert that decreasing the rate any further will likely require novel approaches (3). Although assigning mortality to CLABSIs may be challenging, one recent meta-analysis of 13 pediatric studies reported an 8% pooled mortality rate (6). It seems increasingly apparent that gains in decrease CLABSI and its associated mortality will require further decrease in device utilization. Could further avoidance of central line placement in a cohort of patients be the answer?

The nature of the shock is likely a key determinant in the duration of vasopressor requirement and thus identifying who will ultimately require a central line placement. In the MIS-C cohort, 62% of patients (28) did not require CVC placement (7). This may be more reflective of the nature of MIS-C, where vasoactive infusion requirements may be shorter than many cases of septic shock, as in this cohort, of whom 61% had their vasoactive discontinued within 6 hours. In a single-center retrospective cohort of 102 children, the majority (62%) with septic shock and an overall mortality of 17%, 63% of patients required a CVC (8). Another cohort of 49 pediatric patients with septic shock in the emergency department, of whom 61% of patients ultimately required a CVC (9). The offering from Levy et al (1) adds to this literature, indicating that around half of septic shock patients, especially those who are larger, have lower illness severity, and are not mechanically ventilated, could avoid central lines. In addition, the increased use of PVA in patients with respiratory illness (bronchiolitis or LRTI) in their cohort could indicate that this group may do well avoiding CVCs. To take this logic even further, one wonders how often our avoidance of peripheral vasoactive use delays the removal of a CVC that is a source of septic shock. Very few of the patients in the article by Peshimam et al (4) had long-term CVCs, and we do not know the proportion in the cohort in Levy et al (1) that did, but increased comfort with peripheral vasoactive use could further decrease our device days by facilitating earlier removal of long-term CVCs for source control.

The decision to place central venous access is one that will depend on many clinical factors—illness severity and vasopressor dose, the risks of sedation and anesthesia, ease of peripheral intravenous catheter access, availability of central venous sites, and the expected duration of the required therapy. A review of the literature to date on peripheral vasoactive administration, taken together with these two important articles (Levy et al [1] and Peshimam et al [4]) in this issue of Pediatric Critical Care Medicine, demonstrate that the practice is common, often necessary to adhere to available guidelines, and likely to be associated with a small degree of risk. This risk must be weighed with the alternatives, but I would argue that increased spotlight on CLABSI and other CVC complications forces us to further work to identify a population of patients who have a high likelihood of a short vasoactive duration, in whom peripheral access will be adequate.

1. Levy RA, Reiter PD, Spear M, et al.: Peripheral Vasoactive Administration in Critically Ill Children With Shock: A Single-Center Retrospective Cohort Study. Pediatr Crit Care Med 2022; 23:618–625 2. Weiss SL, Peters MJ, Alhazzani W, et al.: Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children. Pediatr Crit Care Med 2020; 21:e52–e106 3. Hsu HE, Mathew R, Wang R, et al.: Health care-associated infections among critically ill children in the US, 2013-2018. JAMA Pediatr 2020; 174:1176–1183 4. Peshimam N, Bruce-Hickman K, Crawford K, et al.: Peripheral and Central/Intraosseous Vasoactive Infusions During and After Pediatric Critical Care Transport: Retrospective Cohort Study of Extravasation Injury. Pediatr Crit Care Med 2022; 23:626–634 5. Owen VS, Rosgen BK, Cherak SJ, et al.: Adverse events associated with administration of vasopressor medications through a peripheral intravenous catheter: A systematic review and meta-analysis. Crit Care 2021; 25:146 6. Karagiannidou S, Triantafyllou C, Zaoutis TE, et al.: Length of stay, cost, and mortality of healthcare-acquired bloodstream infections in children and neonates: A systematic review and meta-analysis. Infect Control Hosp Epidemiol 2020; 41:342–354 7. D’Souza M, Pye S, Randle E, et al.: Use of peripheral vasoactive drug infusions during the critical care transport of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 infection. Arch Dis Child 2022; 107:e11 8. Patregnani JT, Sochet AA, Klugman D: Short-term peripheral vasoactive infusions in pediatrics: Where is the harm? Pediatr Crit Care Med 2017; 18:e378–e381 9. Kohn-Loncarica G, Hualde G, Fustiñana A, et al.: Use of inotropics by peripheral vascular line in the first hour of treatment of pediatric septic shock: Experience at an emergency department. Pediatr Emerg Care 2022; 38:e371–e377

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