Peripherally administered vasopressin initiated in the emergency department

Single-center, retrospective study

N= 80

To evaluate the incidence of reported infiltrations or extravasations following the administration of peripheral vasopressin

All patients (n= 80)

Adults aged 18 years or older who presented to the ED and received continuous vasopressin via peripheral administration

Patients who initially received vasopressin through a midline or CVC, or if peripheral vasopressin administration could not be verified

Data collected from a single Vermont hospital's electronic health record system. Vasopressin infusion rates ranged from 0.01 to 0.08 units/min, with a median rate of 0.03 units/min. Peripheral IV line location and size were recorded, and concurrent vasopressors were noted. 

Primary: Incidence of reported infiltrations or extravasations

Secondary: Adverse reactions, CLABSI incidence, ICU length-of-stay, discharge disposition

All patients (n= 80)

Age, years (IQR)

Male

Caucasian

Weight, kg (IQR)

Comorbidities

Hypertension

Diabetes

Substance use disorder

Tobacco use

Heart failure

Coronary artery disease

37 (46.3%)

24 (30%)

21 (26.3%)

17 (21.3%)

14 (17.5%)

11 (13.8%)

Admitting Diagnosis

Shock

Respiratory

Cardiac

30 (37.5%)

20 (25%)

20 (25%)

77 (96.3%)

49.8 (13.9-104.1)

All patients (n= 80)

Peripheral IV catheter placement

Above

Antecubital fossa

Forearm

Wrist

Non-arm

Unknown

11 (13.8%)

34 (42.5%)

18 (22.5%)

6 (7.5%)

5 (6.3%)

6 (7.5%)

Peripheral IV catheter size

16 G

18 G

20 G

22 G

Unknown

2 (2.5%)

41 (51.3%)

12 (15%)

5 (6.3%)

20 (25%)

Median duration of peripheral vasopressin administration, min (IQR)

Reports of infiltration or extravasation

Transitioned to CVC administration

Ultrasound guidance was used in only 11.3% (9/80) of the catheter insertions, suggesting limited use of this technique which could potentially enhance accuracy and reduce complications.

Arterial lines were placed in 42.5% (34/80) of patients, with a significant subset (35.3%, 12/34) having the arterial line positioned in the same extremity as the peripheral vasopressin infusion.

No reports of infiltration, extravasation, or other related complications.

No evidence of CLABSI or adverse reactions such as thrombophlebitis, IV site blisters, erythema, swelling, pain, or the need for IV site replacement.

With no observed instances of infiltration, extravasation, or other related complications, peripheral administration of vasopressin initiated in the ED for select, hemodynamically compromised patients may represent a feasible approach to initiate early vasopressor therapy while allowing clinicians to more carefully weigh the risks and benefits of CVC placement.

Safety of Peripheral IV Administration of Vasopressin

Single-center, retrospective, observational cohort study, published as a conference abstract (CHEST 2025 poster)

N= 76

To assess the safety of continuous peripheral vasopressin infusions in critically ill patients with shock

Medical ICU patients receiving a continuous peripheral IV vasopressin infusion for shock, with or without other peripheral vasopressors, from April to September 2024

Investigators retrospectively reviewed medical ICU patients who received vasopressin through a peripheral IV catheter. Data sources were the medication administration record (MAR), line/drain/airway (LDA) nursing assessments, and individual chart review. When the MAR was unclear about catheter type, the infusion route was determined from imaging or provider orders.

Data collected included infusion duration, site of administration, concentration, rate, patient demographics, adverse events (particularly extravasation), ICU length of stay, and hospital disposition. Analysis was descriptive only. The facility’s peripheral-vasopressor protocol (for example, site checks or maximum duration) and the definition of extravasation were not described.

Primary: Extravasation events

Secondary: Infusion characteristics: duration, site, catheter gauge, concentration, and rate; ICU length of stay and hospital discharge status

All patients (n= 76)

All patients (N= 76)

Peripheral vasopressin was used mainly in two situations: acute decompensation needing rapid stabilization before a central line could be placed, and cases with anatomic contraindications to or complications from a central line.

Most common site and catheter: Forearm using a 20-gauge or smaller catheter

No extravasation events reported.

Only 23% of patients were discharged alive; deaths were not attributed to the infusion.

This study demonstrates the safety of peripheral vasopressin infusion in critically ill patients, with no observed extravasation events. A subset of patients received prolonged midline infusions without adverse events. Despite these constraints, the findings support the peripheral administration of non-catecholamine vasopressors as a potential bridge to central access.

Limitations include the study’s retrospective nature, reliance on MAR documentation (with occasional ambiguity regarding catheter type), and dependence on imaging or provider orders to determine infusion routes. Despite these constraints, the findings support the peripheral administration of non-catecholamine vasopressors as a potential bridge to central access. Additionally, this study is available only as a conference abstract, with no peer-reviewed full text. As a result, the methods, definitions, and data are only briefly described, and cannot be fully appraised.

Safety and Outcomes of Peripherally Administered Vasopressor Infusion in Patients Admitted with Shock to an Intensive Cardiac Care Unit—A Single-Center Prospective Study

Single-center prospective study

N= 1100

To evaluate whether the administration of vasopressors through a peripheral venous catheter (PVC) is a safe and effective alternative for the management of patients with cardiogenic shock (CS) presenting to the intensive cardiovascular care unit (ICCU)

PVC group (n= 108)

CVC group (n= 31)

Age ≥18 years; presented with hemodynamic shock requiring vasopressor administration

Patients <18 years old and pregnant women

Vasopressors were administered via PVC or CVC based on the discretion of the treating physician. Noradrenaline was the primary vasopressor used. The PVC was placed in a vein proximal to the wrist with a 20 G cannula. CVC was inserted under ultrasound guidance. Data were collected prospectively and documented in an electronic case report form.

Primary: Central-line-associated bloodstream infection (CLABSI), phlebitis, extravasation, bleeding

PVC (n= 108)

72 ± 12.3

Female

Comorbidities

Hypertension

Diabetes mellitus

Hyperlipidemia

Smoking

Prior CAD

CVA

68%

43%

51%

15%

42%

9%

54%

54%

52%

23%

38%

16%

Shock type

Cardiogenic

Septic

Combined

Hemorrhagic

84%

10%

3%

3%

90%

0%

6%

0%

Number of vasopressors used

1

2

>2

88%

8%

4%

48%

42%

10%

Vasopressor

Norepinephrine

Dopamine

Phenylephrine

Vasopressin

Epinephrine

95%

9%

6%

5%

2%

87%

19%

19%

26%

6%

Norepinephrine dose, mcg/min

1-10

11-20

21-30

31-40

41-60

47%

14%

14%

5%

21%

19%

7%

15%

11%

48%

PVC (n= 113)

Abbreviations: CAD= coronary artery disease; CVD= cerebrovascular disease; NE= norepinephrine; NS= not significant

Although small, there was a higher rate of local adverse events seen at higher NE doses (41–60 mcg/min) of noradrenaline when compared to lower doses. All cases were managed conservatively.

The administration of vasopressor infusions via PVC for the management of patients with CS is feasible and safe in patients with cardiogenic shock. Further studies are needed to establish this method of treatment.

The study was not randomized, and the administration of vasopressors was at the discretion of the senior cardiologist, which may have caused a selection bias. The study's primary goal was not to prove the superiority of a PVC over a CVC, but to evaluate the safety and efficacy of the PVC approach. The etiologies leading to the CS were not analyzed, and there was no long-term follow-up.

There was no specific information on vasopressin dosage or infusion rate.

Skin necrosis after extravasation of low-dose vasopressin administered for septic shock

Design

Case report

Case presentation

A 46-year-old female patient without significant prior medical history underwent an elective laparotomy with lysis of adhesions for chronic abdominal pain. Postoperatively, her clinical course was complicated by Escherichia coli bacteremia, acute renal failure, and acute respiratory distress syndrome (ARDS), necessitating endotracheal intubation, mechanical ventilation, broad-spectrum antimicrobial therapy, and hemodialysis. Despite aggressive respiratory support measures including high positive end-expiratory pressure (PEEP), prone positioning, and temporary neuromuscular blockade, she developed severe refractory hypoxemia requiring tracheostomy and prolonged ventilation.

On intensive care unit (ICU) day 39, shortly before planned transfer to a chronic ventilator facility, the patient acutely developed signs suggestive of sepsis with tachypnea (37 breaths/min), tachycardia (134 bpm), fever (38.4°C), hypotension (79/50 mm Hg), and delirium. Imaging revealed a new left lower lobe consolidation, and sputum and blood cultures confirmed Pseudomonas aeruginosa infection. Hemodynamic instability persisted despite intravenous fluids, high-dose dobutamine infusion (20 mcg/kg/min via a central venous catheter), and catecholamine support, prompting initiation of vasopressin at 0.04 units/min infused peripherally via an 18-gauge catheter in the left wrist.

Following initiation of peripheral vasopressin infusion, the patient developed an 8 x 18 cm irregular erythematous patch with central necrosis near the infusion site within 23 hours. This skin injury evolved despite early catheter removal and supportive measures including elevation and warm compresses. The local skin changes progressed to bullae formation, superficial erosions, and eventual extensive skin sloughing with granulation tissue evident by day 21, although systemic perfusion to distal extremities remained intact. The lesion was managed conservatively without need for skin grafting.

Study Author Conclusions

This detailed clinical report underscores a significant adverse event associated with the peripheral administration of low-dose vasopressin in septic shock management, specifically severe ischemic skin necrosis due to extravasation into local soft tissue from a peripheral venous catheter. While catecholamines such as dopamine and norepinephrine are well-established to carry risks of tissue ischemia when infiltrated, necessitating routine central venous administration, vasopressin has traditionally raised concerns mainly at high doses due to coronary vasoconstriction and resultant myocardial ischemia. High-dose vasopressin, used predominantly in acute variceal bleeding (doses ranging from 0.2 to 1.5 units/min), has been linked to cardiac ischemic events including angina, arrhythmias, and ECG changes. However, low-dose vasopressin (approximately 0.04 units/min) for vasodilatory septic shock has not been associated with clinically significant myocardial ischemia nor distal extremity ischemia or gangrene when administered centrally, supported by randomized and observational studies involving ECG monitoring.

Critically, this case reveals that even at low doses, vasopressin can cause catastrophic local ischemic injury when administered peripherally, despite the minimal volume of infiltration. Such skin necrosis was not reported in prior studies where central venous infusion was the standard, highlighting the importance of administration route. The pathophysiology may relate to prolonged exposure of a larger tissue surface area to circulating vasopressin during continuous infusion as opposed to concentrated bolus exposure in subcutaneous uses (e.g., diabetes insipidus treatment), where high doses are safely given without necrosis. In addition, vasopressin’s differing hemodynamic effects in vasodilatory shock versus normotensive or cardiogenic shock states may influence local vascular responses and tissue tolerance.

The infusion pump’s occlusion pressure monitor did not trigger due to the low infusion rates characteristic of vasopressin dosing in septic shock, possibly delaying detection of extravasation. Currently, there is no effective medical treatment for vasopressin-induced skin necrosis other than immediate discontinuation of the drug, with surgical debridement being necessary in severe cases. Although vasodilators like topical nitroglycerin could theoretically enhance tissue perfusion, their use is limited by the risk of exacerbating hypotension in critically ill patients.

This case has led to institutional policy changes prioritizing central venous catheter administration of vasopressin to mitigate the risk of such ischemic complications. Peripheral venous use is now reserved only for exceptional circumstances with extreme caution. The findings also emphasize that vasopressin pharmacodynamics may differ substantially across patient populations and clinical states, warranting further investigation. Overall, low-dose vasopressin remains a valuable agent for catecholamine-resistant vasodilatory septic shock, given its efficacy in restoring blood pressure and its minimal risk of myocardial ischemia when centrally administered. However, this adverse event clearly delineates a safety profile that necessitates central venous delivery to prevent severe local tissue injury.

Development of cutaneous gangrene during continuous peripheral infusion of vasopressin

Design

Cases 1, 2, and 3

Three patients receiving continuous intravenous vasopressin infusion at a dose of 20 units/hour developed localized cutaneous necrosis near the catheter insertion site after a 24-hour infusion period.

The first patient exhibited a 5 x 2 cm necrotic lesion immediately proximal to the intravenous catheter site, with no signs of subcutaneous extravasation of vasopressin. Management was conservative, involving local dressings, and complete healing was achieved without surgical intervention within four weeks.

Similarly, two additional patients experienced comparable-sized necrotic lesions after the same vasopressin dosing and infusion duration. Both cases healed by secondary intention over a six-week timeframe. This pattern suggests a potential localized vasopressor-induced ischemic injury attributable to vasopressin's potent vasoconstrictive effects, even in the absence of extravasation.

Case 4

The case involves an obese female patient with challenging venous access who received vasopressin infusion at a dose of 20 units/hour via a catheter placed in the long saphenous vein of the left leg. After 24 hours of administration, the patient developed an extensive mottled discoloration along the catheterized vein extending above the knee. This cutaneous manifestation progressed to gangrene, necessitating initial wound care with local dressings followed by split-thickness skin grafting 41 days later. Unfortunately, the patient's clinical course culminated in death 48 hours post-skin grafting due to a massive pulmonary embolism.

Case 5

A patient receiving a vasopressin infusion at a concentration of 20 units/hour via a vein in the left antecubital fossa experienced significant extravasation of the infusion after 18 hours. This complication led to the development of a sizeable area of pale, cold, and mottled skin measuring approximately 8 x 6 x 10 cm, which progressed to gangrene. The lesion was categorized as severe (Child’s grade C), indicating extensive tissue damage.

Treatment efforts included local dressings and, in some cases, split-thickness skin grafting was considered necessary for wound closure and healing. Multiple anatomical sites were involved, including the right and left forearms and left lower leg, with varying outcomes from healing by secondary intention to eventual mortality. Unfortunately, the patient died four days following the onset of gangrene, secondary to repeated variceal hemorrhages and complications such as pulmonary embolism occurring 48 hours postoperatively.

Study Author Conclusions

The vasoconstrictive properties of vasopressin are not limited to the splanchnic circulation, underscoring its systemic vascular effects. Among nine reported cases involving vasopressin infusion, five patients exhibited evident subcutaneous extravasation of the infusion fluid, with only one patient explicitly documented (case 5) to develop overt extravasation. The pathophysiology underlying extravasation in the remaining patients remains unclear, though possible mechanisms include subclinical extravasation or transvascular diffusion of vasopressin secondary to compromised venous flow. Notably, no consistent risk factors were identified upon review of these cases and four additional previously published reports, despite some patients having comorbid conditions such as diabetes mellitus or hypertension. Importantly, none of the patients in this series developed gas gangrene attributable to clostridial sepsis, a complication documented in past reports but absent here.

Historically, prior to 1980, vasopressin was administered via bolus infusion (20 units over 20 minutes every 3 to 4 hours), during which no instances of cutaneous gangrene were observed. Since transitioning to continuous infusion after 1980—administered approximately 200 times—many patients required central venous catheterization primarily for hemodynamic monitoring, and this central route has become the preferred method for vasopressin delivery to reduce local tissue complications.

When peripheral vein administration of vasopressin is unavoidable, stringent precautions are recommended. The infusion site and catheter should be covered with transparent sterile dressings rather than traditional bandages to allow continuous visual inspection. Nursing staff must conduct hourly assessments for early signs of local ischemia, particularly skin blanching, which should prompt immediate cessation of the infusion. Given the absence of a specific antagonist for vasopressin’s vasoconstrictive effects, the authors advocate for immediate catheter flushing with a vasodilator upon suspicion of extravasation to mitigate tissue injury.

Overall, vasopressin therapy should be reserved for cases where absolutely necessary and preferentially administered via a central venous catheter to minimize the risk of local vascular complications. Safety monitoring and vigilance for extravasation are critical components of care, especially considering that formal regulatory bodies and manufacturers have not yet received reports documenting these adverse events, highlighting potential underrecognition in clinical practice.