Annals of the American Thoracic Society

To the Editor:

Intravenous vasopressors are traditionally delivered via central venous access, given concern for extravasation and tissue injury with peripheral administration (1, 2). However, recent studies suggest peripheral administration is safe (35), can shorten the time to vasopressor initiation (6), and can obviate the need for central access in some patients (7, 8). As such, peripheral initiation may shorten the time to shock control and avoid complications associated with central access.

On the basis of these data, the 2021 Surviving Sepsis Campaign guidelines suggest initiating vasopressors peripherally rather than delaying administration until central access is obtained, but still suggest central administration as soon as feasible (9). The guidelines also suggest invasive blood pressure monitoring with arterial catheters for patients receiving vasopressors (9), though arterial catheter use varies widely in practice (10). Given traditional teaching that vasopressors must be administered centrally and should be monitored invasively, it is unclear whether hospital policies permit peripheral vasopressor administration or noninvasive blood pressure monitoring in patients treated with vasopressors. We sought to assess hospital policies on vasopressor administration and monitoring.

Methods

In the fall of 2021, we surveyed 62 hospitals participating in the Michigan HMS (Hospital Medicine Safety Consortium), a Collaborative Quality Initiative sponsored by BCBSM (Blue Cross Blue Shield of Michigan) and Blue Care Network (11). Participation in HMS is mandatory for hospitals enrolled in BCBSM’s Value-based Reimbursement Program, which includes most large hospitals in the state. HMS surveys member hospitals twice yearly on care structures and processes. Surveys are completed by each hospital’s designated HMS representative, who compiles answers from providers at their institution. The survey questions regarding hospital vasopressor policies are available online (https://mi-hms.org/sites/default/files/2021%20Fall%20HMS_Quality_Improvement_Survey_Sepsis.docx).

We classified vasopressor policies as “central-only,” “central-preferred,” or “peripheral-friendly.” Central-only policies recommended central administration except during cardiopulmonary resuscitation (CPR) and provided no guidance regarding peripheral administration. Central-preferred policies recommended central administration except during CPR but still provided guidance on peripheral administration. Peripheral-friendly policies allowed peripheral administration for situations outside of CPR. We compared the presence and type of vasopressor policy by hospital characteristics using Fisher’s exact tests and one-way analysis of variance with a P value threshold of <0.05. Data analysis was completed in StataMP version 17.0 (StataCorp). The study was deemed exempt by the University of Michigan Institutional Review Board.

Results

All 62 (100%) hospitals participating in HMS in the fall of 2021 completed the survey. Hospitals were 79.0% metropolitan, 75.8% teaching, and 91.9% nonprofit (Table 1). The median bed size was 292 (range, 25–1,109 beds).

Table 1. Hospital policies on route of vasopressor administration, by hospital characteristics

 All Hospitals in the Cohort (N = 62)Hospitals with any Vasopressor Policy (n = 52)Hospitals with Specific Types of Vasopressor Policies*
Central-only (n = 13)Central-preferred (n = 19)Peripheral-friendly (n = 19)
Hospital bed size, median (IQR)292 (185, 404)304 (188, 402)222 (139, 324)360 (228, 404)304 (158, 497)
Urbanicity, n (%)     
 Metropolitan49 (79.0)44 (84.6)§9 (69.2)§18 (94.7)§16 (84.2)
 Micropolitan10 (16.1)6 (11.5)§3 (23.1)§0 (0)§3 (15.8)
 Rural3 (4.8)2 (3.9)§1 (7.7)§1 (5.3)§0 (0)
Nonprofit, n (%)57 (91.9)47 (90.4)12 (92.3)16 (84.2)18 (94.7)
Teaching hospital, n (%)47 (75.8)41 (78.9)9 (69.2)16 (84.2)15 (79.0)
CMI, median (IQR)1.74 (1.55, 1.89)1.74 (1.55, 1.88)1.71 (1.50, 1.97)1.79 (1.65, 1.86)1.64 (1.55, 1.84)

Definition of abbreviations: CMI = case mix index; IQR = interquartile range.

*Vasopressor policies were classified into three groups. “Central-only” policies recommended central vasopressor administration except during cardiopulmonary resuscitation and provided no guidance regarding peripheral administration. “Central-preferred” policies recommended central vasopressor administration except during cardiopulmonary resuscitation but also provided guidance on peripheral administration. “Peripheral-friendly” policies allowed peripheral vasopressor administration for situations outside of cardiopulmonary resuscitation. One hospital reported a vasopressor policy but did not provide details about the policy and was not classified into a category.

Hospital bed size was determined using the 2019 Michigan Certificate of Need Annual Survey, Basic Total Licensed Beds Utilization Statistics. Retrieved April 21, 2021, from https://www.michigan.gov/documents/mdhhs/Report_010_Hospital_Beds_by_HSA_703357_7.pdf.

Hospital urbanicity was determined using 2020 U.S. census data and definitions. Hospitals were classified as metropolitan if they were located in an area with at least one city or urbanized area of 50,000 or more inhabitants; micropolitan if they were located in an area with a cluster of at least 10,000 but less than 50,000 inhabitants; and rural if they were located in an area that did not meet the above definitions for metropolitan or micropolitan.

§Indicates statistically significant results on the basis of P < 0.05. All results without an § are not statistically significant by Fisher’s exact test for categorical variables or analysis of variance for continuous variables, using a P value threshold of <0.05.

Hospital ownership (nonprofit vs. for-profit) and teaching status (teaching hospital vs. nonteaching hospital) were determined using American Hospital Association definitions and data obtained from the American Hospital Association’s Data Hub, retrieved April 28, 2021, from https://guide.prod.iam.aha.org/guide/.

CMI was determined using the Centers for Medicare and Medicaid Services CMI file for Financial Year 2021. CMI was missing from two hospitals.

Most hospitals (52 [83.9%]) had a policy on vasopressor administration, of which 13 (25.0%) policies were central-only, 19 (36.5%) central-preferred, and 19 (36.5%) peripheral-friendly (Figure 1). Presence and type of vasopressor policy varied by urbanicity but not by other hospital characteristics. Vasopressor policies were present in 89.8% of metropolitan hospitals versus 60.0% micropolitan versus 66.7% rural; P = 0.029. Policies were central-only in 18.4% of metropolitan hospitals versus 30.0% micropolitan versus 33.3% rural; P = 0.047.

The 38 policies that provided guidance on peripheral vasopressor administration limited peripheral infusion on the basis of vasopressor and/or peripheral access characteristics (Figure 2). Thirty-four (89.5%) limited the duration of peripheral infusion; 17 (44.7%) limited the dosage allowed peripherally; 22 (57.9%) limited which agent(s) could be infused peripherally; 14 (36.8%) limited peripheral infusion to a single vasopressor agent at a time; 20 (52.6%) specified a minimum-sized peripheral catheter (PIV); 20 (52.6%) limited site of peripheral infusion; 24 (63.2%) required monitoring of PIVs during infusion; and 8 (21.1%) required ultrasound-guided placement and/or confirmation of PIVs (Figure 2). Duration limits ranged from until central venous catheter placement to 48 hours. Vasopressin was the most commonly prohibited agent, followed by epinephrine. Leg, hand, and wrist were the most commonly prohibited intravenous locations for peripheral vasopressor infusion.

A minority of hospitals (27 [43.5%]) had policies regarding invasive blood pressure monitoring via arterial catheters for patients treated with vasopressors. Of these, 4 (14.8%) required and 11 (40.7%) suggested invasive monitoring. The remainder (12 [44.4%]) recommended arterial catheter placement at the discretion of the treating clinicians.

Discussion

In this survey of 62 diverse Michigan hospitals, we show that most hospitals have policies guiding the route of vasopressor administration. However, the content of these policies differs markedly, ranging from requiring vasopressors to be delivered centrally to allowing peripheral vasopressors with a range of limitations. Policies regarding vasopressor monitoring are less common, with few hospitals requiring invasive blood pressure monitoring.

The variability of hospital policies likely reflects the accruing but incomplete data on the optimal safety and monitoring criteria for peripheral vasopressor administration. Observational studies, including a large prospective single-center cohort (7) and several meta-analyses (35), show low rates of adverse events with peripheral vasopressor administration. However, these cohorts generally used short durations of peripheral administration, such as perioperatively (12), or involved multifaceted safety protocols, including frequent nursing monitoring and placement and/or confirmation of the PIV by ultrasound (7, 13). The safety of peripheral vasopressor administration in the context of routine care or relaxed safety protocols is unclear, and there is little available information about how peripheral vasopressors are used in practice.

A second finding of our study was that hospital policies differed by urbanicity but not other hospital characteristics. While we are unable to confirm the reason for this association, we hypothesize there may be fewer resources to develop and update policies at micropolitan or rural hospitals.

Limitations

There are several limitations to this study. First, while HMS hospitals are diverse across many characteristics, generalizability may be limited by the single-state data and the smaller number of rural and critical-access hospitals within HMS. Second, we were unable to assess variation in individual provider practices but speculate these are likely shaped by local policies. Third, we were unable to examine the extent to which hospital practices adhere to hospital policies. Fourth, with 62 hospitals, we had limited power to assess for differences in policies by hospital characteristics.

Conclusions

Overall, the variability in hospital policies suggests wide variation in practice. Hospitals should consider updating policies to permit peripheral vasopressors in scenarios in which their use has been shown to be safe: for short periods or longer durations with the use of multifaceted safety protocols.

The authors thank all Hospital Medicine Safety Consortium member hospitals, Elizabeth McLaughlin, Scott Flanders, Jennifer Horowitz, Tawny Czilock, and Jennifer Minock.

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2. Loubani OM, Green RS. A systematic review of extravasation and local tissue injury from administration of vasopressors through peripheral intravenous catheters and central venous catheters. J Crit Care 2015;30:653.e9653.e17.
3. Tran QK, Mester G, Bzhilyanskaya V, Afridi LZ, Andhavarapu S, Alam Z, et al. Complication of vasopressor infusion through peripheral venous catheter: a systematic review and meta-analysis. Am J Emerg Med 2020;38:24342443.
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6. Delaney A, Finnis M, Bellomo R, Udy A, Jones D, Keijzers G, et al. Initiation of vasopressor infusions via peripheral versus central access in patients with early septic shock: a retrospective cohort study. Emerg Med Australas 2020;32:210219.
7. Cardenas-Garcia J, Schaub KF, Belchikov YG, Narasimhan M, Koenig SJ, Mayo PH. Safety of peripheral intravenous administration of vasoactive medication. J Hosp Med 2015;10:581585.
8. Ricard JD, Salomon L, Boyer A, Thiery G, Meybeck A, Roy C, et al. Central or peripheral catheters for initial venous access of ICU patients: a randomized controlled trial. Crit Care Med 2013;41:21082115.
9. Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med 2021;49:e1063e1143.
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11. Blue Cross Blue Shield of Michigan and Blue Care Network. Collaborative quality initiatives. [accessed 2022 Jan 4]. Available from: https://www.valuepartnerships.com/programs/collaborative-quality-initiatives/.
12. Pancaro C, Shah N, Pasma W, Saager L, Cassidy R, van Klei W, et al. Risk of major complications after perioperative norepinephrine infusion through peripheral intravenous lines in a multicenter study. Anesth Analg 2020;131:10601065.
13. Delgado T, Wolfe B, Davis G, Ansari S. Safety of peripheral administration of phenylephrine in a neurologic intensive care unit: a pilot study. J Crit Care 2016;34:107110.
*Corresponding author (e-mail: ).

Supported by the Blue Cross Blue Shield of Michigan Foundation (BCBSM) and Blue Care Network as part of the BCBSM Value Partnerships Program. This manuscript does not represent the views of the Department of Veterans Affairs (VA) or the U.S. government. This material is the result of work supported by resources and the use of facilities at the Ann Arbor VA Medical Center.

Author Contributions: E.M. and H.C.P. contributed to the study design, data acquisition, analysis and interpretation, and drafting and revision of the manuscript. D.C., M.T.-K., G.T., J.B., and J.I.M. contributed to data interpretation and revision of the manuscript for intellectual content. All authors approved this manuscript for submission.

Author disclosures are available with the text of this letter at www.atsjournals.org.

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