2021 Update: What are considerations for determining whether a drug may be administered via a midline catheter?
Midline catheters represent a unique vascular access device (VAD) for patients requiring intravenous (IV) administration of drugs or other infusates.1,2 After their introduction in the 1950s, hypersensitivity and phlebitis reactions to the manufacturing materials led to a temporary decline in the use of midline catheters through the 1990s; however, a redesign of these products in recent years has led to their renewed adoption. Midline catheters have properties that differ from both those of traditional peripheral IV catheters and central venous catheters (CVCs). Therefore, questions often arise regarding the appropriateness of administering specific drugs via midline catheter. This review provides an overview of midline catheters and a summary of properties that influence the determination of whether a drug is appropriate for administration via midline catheter.
Properties of midline catheters
Midline catheters differ from other VADs with regard to their insertion and termination sites.1,3 Midline catheters are inserted peripherally into the antecubital fossa or upper arm via the basilic, cephalic, or brachial vein, and extend from 8 to 20 cm centrally, where the catheter tip terminates at or below the axillary vein. Because this termination site is distal to those of CVCs and peripherally inserted central catheters (PICCs), midline catheters are not considered to dwell in the central circulation.1 Whereas the central termination site of CVCs and PICCs provide the ability to administer a wider range of infusates (eg, vesicants), this is not recommended with VADs terminating distal to the central circulation. Central VADs may also be more appropriate in patients needing longer-term therapy.3 Although some evidence has supported lower thrombosis risk with midline catheters compared with CVCs,1 a recent systematic review of 12 studies in 40,871 patients found that risk of venous thromboembolism was significantly higher with a midline catheter compared with a PICC (3.97% versus 2.29%; relative risk, 1.53; 95% CI, 1.33 to 1.76; p<0.00001).4 However, evidence evaluating the risk of catheter-related bloodstream infections (CRBSI) continues to find similar or improved rates of infection with midline catheters compared with PICCs.5
Compared with midline catheters, peripheral IV catheters are inserted more distally and most often utilize veins of the dorsum of the hand for cannulation.1-3 Peripheral IV catheters have high first-attempt failure rates (26% in adults, 54% in children) and often require recannulation in larger more proximal sites.1,2 Therefore, midline catheters may reduce the need for recannulation and thereby afford a longer dwell time. Additionally, patient mobility is greater with midline catheters because of the location of their insertion site.2 Lastly, compared with drug administration via peripheral IV catheter, the risk of phlebitis may be reduced with administration via midline catheter because of its termination in an area with a higher rate of blood flow.2 The rates of CRBSI have also been reported to be lower with midline versus peripheral catheters (0 to 0.2 versus 0.5 per 1,000 catheter days).1
Overall, the properties of midline catheters may make them preferable for specific durations of therapy. In 2021 the Infusion Nurses Society (INS) updated their 2016 guidelines and recommended consideration of midline catheters when the anticipated duration of therapy was 5 to 14 days with a preference for peripheral catheters for shorter durations of therapy and CVCs when longer durations of therapy are required.6 A recent study supports use of midline catheters for prolonged courses of therapy up to 14 days, but there remains limited data for use of midline catheters beyond 2 weeks.7 Currently, the CDC recommends consideration of midline catheters when the duration of IV therapy is likely to exceed 6 days.1,8
Considerations for drugs administered via midline catheter
The main consideration in determining whether a drug is appropriate for administration via midline catheter is its propensity for causing phlebitis.2 Phlebitis is inflammation of a vein caused by damage to the tunica intima, which may be accompanied by erythema, swelling, pain, heat, and a palpable cord if thrombosis is present. If chemical phlebitis occurs, consideration should be given to the need for alternative vascular access, an alternative medication, a slower infusion rate, or further dilution of the medication.6
Chemical phlebitis may be caused by drugs that irritate the vasculature, usually because of extremes of pH or osmolarity.3 Infusates with an osmolarity over 600 mOsm/L are associated with symptoms when extravasation occurs, and those over 800 mOsm/L are usually recommended to be given via a CVAD.9 Infusates with a pH between below 5.5 or above 8.5 can cause tissue damage, with alkaline agents generally producing worse toxicity than acidic agents. The 2021 INS guidelines recommend against the use of midline catheters for continuous administration of vesicant therapy, parenteral nutrition, or other infusates with “extremes” of pH or osmolarity.6 Although the “extremes” are not further defined, the guidelines specifically recommend central lines for parenteral nutrition formulas with osmolarity exceeding 900 mOsm/L. Lastly, they recommend avoidance of midline catheters in patients with a history of thrombosis, hypercoagulability, venous stasis, or with a need to preserve vein integrity, such as in patients with end-stage renal disease.
There is not a comprehensive list of drugs that are appropriate for administration via midline catheter. Clinicians considering drug administration via this VAD should review the chemical properties of the drug under consideration from reputable resources (eg, prescribing information) to compare them with the guidance above. Nonetheless, a review of literature of known vesicants and drugs reported to cause vascular injury or extravasation indicates some drugs that may present higher risk when administered via midline catheter. For example, many cytotoxic agents (ie, chemotherapy) are considered vesicants and should not be administered via midline catheters according to INS standards.10,11 Additionally, in 2017, the INS assigned a Vesicant Task Force to publish a list of noncytotoxic vesicant medications and solutions.11 The Table below, while not exhaustive, details drugs from this list, as well as drugs that have extremes of pH or osmolarity that have been associated with vascular injury or extravasation.8,9
|Table. Noncytotoxic vesicants and drugs with extremes of pH or osmolarity reported to cause vascular injury or extravasation.3,6,9,11,12
|Noncytotoxic vesicants||Hyperosmolar agents||Acidic and alkaline agents
|Amiodarone||Yellow||Calcium chloride 10%||2040||Aminophylline||8.8
|Arginine||Yellow||Calcium gluconate||Varies by concentration||Amiodarone||3.5-4.5
|Calcium chloride||Red||Contrast media||Variesb||Atracurium||3.0-3.65
|Calcium gluconate||Red||Dextrose 10%-50%||504-2520||Conivaptan||3.4-3.8
|Contrast media, nonionic||Red||Diazepam 0.5%||NR||Doxycycline||1.8-3.3
|Dextrose ≥10%-12.5%||Yellow||Hypertonic saline||Varies by concentration||Furosemide||8.0-9.3
|Dextrose ≥12.5%||Red||Magnesium sulfate 15%-50%||580-4060||Ganciclovir||11
|Epinephrine||Red||Potassium ≥60 mEq/L||≥763||Nicardipine||3.5
|Mannitol ≥20%||Yellow||Sodium bicarbonate 8.4%||2000||Phenobarbital||9.2-10.2
|Nafcillin sodium||Yellow||TPN||Commonly >900||Phenytoin||10-12
|Norepinephrine||Red|| || ||Promethazine||4.0-5.5
|Pentamidine isethionate||Yellow|| || ||Sodium thiopental||10-11
|Pentobarbital sodium||Yellow|| || ||Vancomycin||4
|Phenobarbital sodium||Yellow|| ||
|Potassium ≥60 mEq/L||Yellow|
|Sodium chloride ≥3%||Red|
|TPN >900 mOsm||Red|
|aRisk level was assigned based on literature reports of peripheral administration. Risk level of red indicates higher risk and greater literature documenting tissue damage upon extravasation. Risk level of yellow indicates intermediate risk and less literature documenting tissue damage upon extravasation.
bOsmolarity varies. For further information, see American College of Radiology guideline.13
Abbreviations: NR=not reported; TPN=total parenteral nutrition.
One drug that has generated controversy regarding its appropriateness for administration via midline catheter is vancomycin. Based on the range of pH values generally considered appropriate for midline administration, vancomycin would be excluded because of its pH of 4. However, the INS Task Force identified limited literature describing extravasation of vancomycin. Furthermore, in vitro evidence suggested that vancomycin-associated endothelial damage is caused by factors other than pH. Additionally, the risk of cytotoxicity is reduced by intermittent compared with continuous infusion, as well as by dilution of vancomycin to concentrations of 2 to 5 mg/mL. One randomized controlled trial found that the incidence of total complications, phlebitis, and thrombosis did not significantly differ when vancomycin was administered for less than 6 days via midline catheter versus PICC.3,14
Midline catheters have properties unique from those of peripheral and central VADs. Determinations regarding the administration of drugs via midline catheter should consider properties of each drug individually because no definitive guidance is available to list the appropriateness of all drugs. Generally, drugs that are vesicants or have extremes of pH or osmolarity should not be administered via midline catheters.
- Adams DZ, Little A, Vinsant C, Khandelwal S. The midline catheter: A clinical review. J Emerg Med. 2016;51(3):252-258. doi:10.1016/j.jemermed.2016.05.029
- Griffiths V. Midline catheters: indications, complications and maintenance. Nurs Stand. 2007;22(11):48-58. doi:10.7748/ns2007.11.22.11.48.c6241
- Gorski L, Hadaway L, Hagle ME, McGoldrick M, Orr M, Doellman D. Infusion therapy standards of practice. J Infusion Nurs. 2016;39(1S):S1-159.
- Lu H, Yang Q, Yang L, et al. The risk of venous thromboembolism associated with midline catheters compared with peripherally inserted central catheters: A systematic review and meta-analysis [published online ahead of print, 2021 May 15]. Nurs Open. 2021;10.1002/nop2.935. doi:10.1002/nop2.935
- Lu H, Hou Y, Chen J, et al. Risk of catheter-related bloodstream infection associated with midline catheters compared with peripherally inserted central catheters: A meta-analysis [published online ahead of print, 2020 Dec 29]. Nurs Open. 2020;8(3):1292-1300. doi:10.1002/nop2.746
- Gorski LA, Hadaway L, Hagle ME, et al. Infusion therapy standards of practice. J Infus Nurs. 2021;44(suppl 1):S1-S224. doi:10.1097/NAN.0000000000000396
- Seo H, Altshuler D, Dubrovskaya Y, et al. The safety of midline catheters for intravenous therapy at a large academic medical center. Ann Pharmacother. 2020;54(3):232-238. doi:10.1177/1060028019878794
- Intravascular catheter-related infection (BSI). Centers for Disease Control and Prevention. Updated July 2017. Accessed August 2, 2021. https://www.cdc.gov/infectioncontrol/guidelines/BSI/index.html
- David V, Christou N, Etienne P, et al. Extravasation of noncytotoxic drugs. Ann Pharmacother. 2020;54(8):804-814. doi:10.1177/1060028020903406
- Boulanger J, Ducharme A, Dufour A, et al. Management of the extravasation of anti-neoplastic agents. Support Care Cancer. 2015;23(5):1459-1471. doi:10.1007/s00520-015-2635-7
- Gorski LA, Stranz M, Cook LS, et al. Development of an evidence-based list of noncytotoxic vesicant medications and solutions. J Infus Nurs. 2017;40(1):26-40. doi:10.1097/NAN.0000000000000202
- Reynolds PM, MacLaren R, Mueller SW, Fish DN, Kiser TH. Management of extravasation injuries: a focused evaluation of noncytotoxic medications. Pharmacotherapy. 2014;34(6):617-632. doi:10.1002/phar.1396
- ACR Committee on Drugs and Contrast Media. ACR manual on contrast media. American College of Radiology. Updated January 2021. Accessed August 2, 2021. https://www.acr.org/-/media/ACR/Files/Clinical-Resources/Contrast_Media.pdf
- Caparas JV, Hu JP. Safe administration of vancomycin through a novel midline catheter: a randomized, prospective clinical trial. J Vasc Access. 2014;15(4):251-256. doi:10.5301/jva.5000220
Ryan Rodriguez, PharmD, BCPS
Clinical Associate Professor, Drug Information Specialist
Courtney Krueger, PharmD, BCPS
Clinical Assistant Professor, Drug Information Specialist
University of Illinois at Chicago College of Pharmacy
The information presented is current as of August 2, 2021. This information is intended as an educational piece and should not be used as the sole source for clinical decision making.