Vasopressor Administration via Peripheral Intravenous Access for Emergency Department Stabilization in Septic Shock Patients

HIGHLIGHT

Patients with septic shock require stabilization with fluid resuscitation, vasopressors, source control, and antimicrobials. Septic shock is a common disease presentation to the ED. In this study, we highlight the safety and efficacy of peripheral vasopressor administration to facilitate rapid hemodynamic stabilization of septic patients in the ED.

INTRODUCTION

Sepsis, a life-threatening syndrome of organ dysfunction due to dysregulated host response, is a leading cause of morbidity and mortality worldwide.^1–3 Current septic shock guidelines recommend initiation of vasopressor agents after adequate volume resuscitation and now include a consideration statement for initiation of PIV vasopressor administration.^4–6 Early vasopressor administration has been associated with improved outcomes including reduced mortality.^7–10

Historically, vasopressors have been administered through a central venous line (CVL) due to the theoretical risk of local tissue ischemia and injury if extravasation occurred from PIV infusion.^11–18 There is also the theoretical concern of losing venous access altogether due to PIV-only placement. However, CVL insertion is a time-consuming process that typically necessitates a physician or advanced-level practitioner for insertion and often requires confirmation by chest radiography for above-diaphragm CVLs.¹⁹ Initiating vasopressors infusion through a more rapidly obtainable PIV prioritizes early hemodynamic stability and organ perfusion over extravasation risk. In sepsis, a time-sensitive diagnosis and treatment paradigm, rapid vasopressor administration appears even more important as it impacts mortality.^7–10

A growing body of evidence from predominately intensive care unit (ICU) and operating room (OR-)-based studies suggests that vasopressors can be administered through a PIV with low rates of extravasation or injury.^20–27 These findings were recently replicated in ED- based studies and in a meta-analysis.^28–30 However, as this practice remains a conditional recommendation in the recent 2021 Surviving Sepsis Guidelines,⁴ there is a need for additional investigation regarding peripheral administration for patients in the ED, specifically with septic shock. Furthermore, among health centers that have embraced PIV vasopressor infusions, there is limited data on how frequently, and under what circumstances, vasopressors are administered initially via PIVs as compared to CVLs or indwelling tunneled lines existing prior to ED arrival (Prior-CVLs). The objective of this study was to evaluate PIV vasopressor infusion practice patterns, potential complications, and patient-centered outcomes among patients with septic shock presenting to a large urban single-center academic ED that had recently transitioned to allowing PIV vasopressor administration.

MATERIALS AND METHODS

This is a single-center, retrospective, observational cohort study of patients presenting to an urban, academic, quaternary-care hospital with septic shock. Our septic shock standing order set includes an order for nursing to obtain PIV access in all patients with either an 18- or 20-gauge standard intravenous catheter being placed in an upper extremity. Further venous access interventions: non-extremity placement, ultrasound-guided access, etc. require discussion with the physician team. Our system order sets for norepinephrine and phenylephrine allow these medications to be administered in a critical care setting (including our ED) through a PIV that “flushes without difficulty”. However, system pharmacy guidelines have set an arbitrary administration ceiling limit of 0.2 µg/kg/min for norepinephrine PIV infusion.

The study received approval from the Institutional Review Board. Patients over 18-years-old admitted via the ED with a diagnosis of septic shock who received a vasopressor infusion in the ED were included. Patients were excluded if they were transferred to the ED from an outside hospital (due to impact on the initial route of vasopressor), had a history of heart failure, or if the patient’s shock was not attributable to sepsis or was due to a mixed shock state. Patient encounters were identified using clinical classifications software (CCS) to try to include a near consecutive sample with the assumption that encounters would be missed if only searching for sepsis or septic shock. Selection of CCS codes for septicemia, pneumonia, peritonitis, intestinal abscess, biliary tract disease, urinary tract infections, skin and subcutaneous tissue infections, and meningitis were used in conjunction with an order in the electronic medical record for an infusion of norepinephrine, phenylephrine, vasopressin, epinephrine, or dopamine to identify patient encounters. Data were collected on patient demographics, vasopressor type and dosages, time to vasopressor initiation, site of vasopressor administration, presumed source, antibiotic administration, the total amount of intravenous fluid administered, and major complications of extravasation and digit ischemic events. Cases were grouped and then analyzed by the site of vasopressor initiation: ED-CVL, PIV, or Prior-CVL. The ED-CVL and PIV groups were compared. Data were analyzed using descriptive statistics as well as statistical analysis with two-tailed t-tests using SPSS. While our comparison focused on the PIV and CVL groups, the prior-CVL group was included for a complete description of the current state of the administration of vasopressors in this cohort.

RESULTS

A total of 136 unique patient encounters were identified, of which 69 were included (Flowchart 1). The most common reasons for exclusion were a history of heart failure²⁶ and shock due to non-septic or mixed shock state.²⁴ Vasopressors were initiated through a PIV in 49.3% of cases and through an ED-CVL in 24.6% of cases. Patients arrived with a usable Prior-CVL in 26.1% of cases. Two patients in the PIV group had interosseous devices (IO) placed due to difficult IV access but subsequently had vasopressors switched from the IO to the PIV route and were included in the PIV cohort.

Patient baseline characteristics are summarized in Table 1. Norepinephrine was the most common first-line vasopressor, used in 85.3% of the PIV group, 100% of the ED-CVL group, and 89% of the Prior-CVL group. Phenylephrine and epinephrine were also administered through the PIV route. The time from arrival to vasopressor initiation was 214.8 minutes for PIVs and 294.7 minutes for ED-CVLs with an absolute difference of 79.9 minutes (p = 0.24) (Table 2). The time to initiation in the Prior-CVL group was 181.2 minutes (much of this cohort were oncologic patients with an existing indwelling venous port available to access). The average ED length of stay was 494.3 minutes for the PIV group, 465.9 minutes for the ED-CVL group, and 461.6 minutes for the Prior-CVL group. The total volume of IV fluid bolus was 2891 mL for the PIV group and 2925 mL for the ED-CVL group (p = 0.9). Antibiotics were given within 6 hours to all patients in the cohort, per existing sepsis guidelines.

In the PIV group, vasopressors were initiated through an IV in the antecubital fossa (AC) or more proximal in 61.9% of patients and distal to the AC in 29.3% of patients, with location not specified in 8.8% of patients. CVLs were subsequently placed in the ED in 73.5% of these PIV patients, with an additional 14.7% having a subsequent CVL placed in the ICU. No CVL was placed in 11.8% of patients in the PIV group, avoiding central line days altogether.

There were no reported extravasation events or digit ischemia in the vasopressors administered through the PIV cohort. There was no reported loss of PIV access or transient hypotension associated with the route of administration. Vasopressor days of 28-day survivors were 2.26 days for the PIV group and 3.14 days for the ED-CVL group, with an absolute difference of 0.88 days (p = 0.05). ICU length of stay of 28-day survivors was 4.44 days for the PIV group and 4.86 days for the ED-CVL group (p = 0.69). Mortality rates at 28 days were 20.6% for PIV and 17.6% for ED-CVL (p = 0.81). The 28-day mortality for the Prior-CVL group was 61.1%.

DISCUSSION

Vasopressor administration is a vital component of the management of septic shock, with prompt initiation associated with reduced mortality.^5–10 While peripheral administration of vasopressors has become more accepted in some clinical locations, data from septic ED patients is limited.²⁹ In addition, limited ED data exists on clinical practice patterns, safety profile, and impact on the patient flow when PIV vasopressor administration is employed.

In this retrospective, an observational study analyzing the initiation of vasopressors in a single quaternary-care ED, the majority of patients without a Prior-CVL presenting for septic shock received initial vasopressors through a PIV. This is an accepted practice pattern at our institution when an appropriate PIV has been obtained. Nursing protocols include instructions on checking the distal infusion limb for signs of ischemia. Norepinephrine comprised the majority of initial vasopressor use in the data cohort, which would be expected as norepinephrine is the first-line agent for septic shock refractory to fluid administration.^31–34 The data also suggested a trend towards a decrease in time to vasopressor initiation by an average of 79.9 minutes in the PIV group compared to the ED-CVL group, though this did not reach statistical significance likely related to the small sample size. Future studies should look at the feasibility of expanding the practice of PIV vasopressor utilization across multiple centers.

There was no ED or ICU documentation of extravasation events or digit ischemia. This finding emulates that of recent studies.^20–30 The majority of PIVs were placed at the AC or proximal which may reduce extravasation risk.²¹ We also report no episodes of loss of intravenous access leading to patient hemodynamic instability, which is often cited as a concern when patients don’t have central access. It is important to note that the patient population from this study was obtained in a “critical care” area of the ED which utilizes a 2:1 or 3:1 nursing ratio. This could limit the generalization of findings in EDs that cannot accommodate these nursing ratios that facilitate more frequent line checks. Furthermore, the safety of this clinical practice may be improved with newer PIV insertion techniques favoring ultrasound guidance.

There was a reduction in vasopressor days when initiated peripherally (absolute difference 0.88 days, p = 0.05), likely driven by the 11.8% of patients who received PIV vasopressors and never underwent central venous catheterization. Of note, one of those four patients received PIV vasopressors for more than 1 day without any documented complication. This subset of patients receiving PIV vasopressors might have been less critically ill than the other cohorts of patients. However, any reduction in central line need is beneficial for patients and for potential complications such as central line-associated bloodstream infections. It should also be noted that vasopressor administration was initiated about an hour earlier in the PIV cohort, thought to be associated with potential delays originating from the time needed to complete the CVL procedure. Patients in the PIV vasopressor group had these medications infused for upwards of 8 hours without limb ischemia. Further studies should look at risk stratifying length of time vs complication risk for PIV vasopressor administration.

Interestingly, 88.2% of patients ultimately ended up with an invasive central line placed, either in the ED or ICU, during their sepsis care. This CVL placement was most likely impacted by an institutional arbitrary upper limit of 0.2 µg/kg/minute for norepinephrine PIV infusion. It is hypothesized that this also negatively impacted the observed ED length of stay as the majority of patients who received CVL catheterization underwent these sterile invasive procedural interventions while in the ED. We did not gather specific procedural times or potential impact on the length of stay. Further studies should look at safety profiles and risk stratification for PIV dosing limits and help guide medication administration guidelines. Without this arbitrary dosing limit, further central line necessity and overall days may have been avoided.

We did not expect to see any impact on mortality by the intervention of PIV vasopressor administration in this small cohort. However, a mortality difference was noted in the 26.1% of patients with a Prior-CVL used for vasopressor administration. This cohort had a 61.1% mortality rate, a value much higher than that of both the PIV and ED-CVL groups as well as the general mortality rates in septic shock patients.³³ We suspect this is likely due to the higher morbidity in this patient population as patients with indwelling lines tend to have a significant underlying illnesses which may overshadow the positive effects of early vasopressor initiation. However, further studies may want to evaluate further sepsis care and treatment goals in this specific patient cohort.

LIMITATIONS

There are several limitations to this study. The retrospective nature of this study is an inherent limitation, and observational studies are at risk for selection and information bias. Data being from a single center may also limit external applicability. A small sample size may result in reduced rates of rare outcomes and complications. Data were gathered by one researcher which may add to information bias. Patients with heart failure or mixed shock were excluded due to the assumption that clinicians may treat these patients differently. However, excluding these patients may reduce applicability to the general ED population.

CONCLUSION

Vasopressors are being effectively initiated and administered through the PIV route for ED septic shock patients. Norepinephrine comprised the large majority of initial vasopressors used in PIVs. There were no documented episodes of extravasation or digit ischemia in the ED or ICU with initial PIV administration. The findings herein provide important baseline data for the clinical utility and safety of PIV initiation and titration of vasopressor administration in ED patients specifically with septic shock. Further studies should assess risk stratification for escalating vasopressor doses and length of exposure time of vasopressors through the PIV route with a potential goal to avoid central venous catheterization in the appropriate patient population.

ORCID

Scott Kilian https://orcid.org/0000-0002-5681-2505

Aaron Surrey https://orcid.org/0000-0001-9846-5938

Weston McCarron https://orcid.org/0000-0002-1358-8128

Kristen Mueller https://orcid.org/0000-0001-9799-0861

Brian Todd Wessman https://orcid.org/0000-0002-8020-2678

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