C O L L E G E O F P H A R M A C Y

Safety and Efficacy of Hypertonic Saline Via Peripheral Venous Catheter and Intraosseous Administration: What is the Evidence? A Literature Review

Emily Farina, Adrianna Goodin, Marissa MauroAdvisor: Amber E. King, PharmD, BCPS, FNAP

Disclosures

• None

Objectives

• Define PICO analysis• Discuss the safety of hypertonic saline

administered via central, peripheral, or intraosseous line• Assess the efficacy of hypertonic

saline administered via central, peripheral, or intraosseous line• Compare efficacy and safety of hypertonic saline

administered via different routes

Background

• Hypertonic saline traditionally administered via central venous catheter1,2• Due to hyperosmolarity• Extrapolated from nutrition literature

• Central venous catheters• 15% complication rate3,4

• Mechanical• Infectious

McGee DC, Gould MK. Preventing complications of central venous catheterization. N Engl J Med. 2003;348:1123-1133.

What is a PICO analysis?• Help define multiple clinical questions• P: Population• Neurocritically ill patients

• I: Intervention• Hypertonic saline administration via peripheral line

• C: Comparison• Mannitol, normal saline, or no drug comparator• Central line, intraosseous line, or no route comparator

• O: Outcome• Efficacy and/or safety data

Safety

Central Line Administration of Hypertonic Saline Safety

• 4 trials report safety data of central line administration of hypertonic saline5-9

• Trials were descriptive• 0 included a comparator• 2 studies reported complications• 13.8% developed DVT

• 8/58 cases

• AKI (but not within 5 hours of HTS use)

• 2 studies reported no complications• No mention of infectious complications

Peripheral Line Administration of Hypertonic Saline Safety

• 13 trials report safety data of peripheral administration of hypertonic saline10-20,5,6

• Trials were descriptive• 5-213 patients included• Pediatrics and adults

• 2 trials included a comparison drug• Routine care solutions• Mannitol

• 3 trials described a comparison line• IO, CVC, or IO and CVC

Peripheral Line Administration of Hypertonic Saline Safety continued

• 8 trials reported no infusion related complications• 5 trials reported infusion related complications • Phlebitis, infiltration, extravasation, pain, erythema,

edema < 1 inch• No significant difference when compared to routine care

solutions

• No incidence of infectious complications with IO, CVC, or PVC

Intraosseous Administration of Hypertonic Saline Safety

• 4 trials described the safety of hypertonic saline administered via intraosseous infusion5,7,12,15

• All trials were descriptive• 5-76 patients included• Pediatrics and adults

• 0 trials included a comparison drug• 1 trial included a comparison line• Central line

• 1 trial denied infectious complications• All trials denied infusion related complications • No depot effect observed

Efficacy

Central Hypertonic Administration Efficacy

• Population:8,13,19

• Refractory acute decompensated HF patients• 150 mL of 3% NaCl over 30 min

• Pediatric patients with traumatic brain injuries (TBIs)• 3%, 23.4% NaCl

• Standard of care: central venous catheters• 3 trials consisting of 26-105 patients• No comparison group• Outcomes• Increased serum sodium levels and net urine output for HF patients• TBIs: 47% patients GCS returned to normal, decrease in

intracranial pressure within one and 4 hr of both single and cluster hypertonic bolus administration

Peripheral Hypertonic Administration Efficacy

• Population:10,20

• Geriatric patients with hyponatremic encephalopathy• Adults with hyponatremia (serum Na <120mEq/L)

• 2 trials consisting of 25-64 patients• 500 mL of 3% HTS• 3% HTS + 1-4 mcg desmopressin

• No comparison group• Outcomes:• CNS symptoms resolved in 97% of encephalopathy cases• Mean increase in sodium levels after 4 & 24 hr was 2.6 & 5.8 mEq/L,

respectively

Intraosseous Administration of Hypertonic Saline Efficacy• Population:7,15

• Critically ill adults with an acute neurologic event that required hyperosmolar therapy

• Adults with clinical and imaging signs of intracranial hypertension

• 2 trials consisting of 5-76 patients• 3% HTS IO infusion at 25-100 mL/hr for 24 hr• 23.4% HTS IO infusion for 3-5 min + 30 mL bolus dose

• IO more rapid route of administration• Serum sodium levels had risen appropriately

• 23.4% HTS associated with smaller increase in mean sodium level

Conclusion

• Based on available literature, there are minimal complications associated with HTS via peripheral and central lines, however the quality of the data is low

• Efficacy data is limited for HTS administration via peripheral, central, and intraosseous administration

• Future RCTs still need to be performed to better assess safety and efficacy outcomes of all routes

• Consider peripheral administration for patients with similar characteristics to those in the studies

Special thanks to Fred Rincon, MD, MSc, MB.Ethics, FACP, FCCP, FCCM

Questions?

References

1. 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.

2. Marko NF. Hyperosmolar therapy for intracranial hypertension: time to dispel antiquated myths. Am J Respir Crit Care Med. 2012;185(5):467-468.

3. McGee DC, Gould MK. Preventing complications of central venous catheterization. N Engl J Med. 2003;348:1123-1133.

4. Comerlato PH, Rebelatto TF, Santiago de Almeida FA, et al. Complications of central venous catheter insertion in a teaching hospital. Rev Assoc Med Bras. 2017;63(7):613-620.

5. Brenkert TE, Estrada CM, McMorrow SP, Abramo TJ. Intravenous hypertonic saline use in the pediatric emergency department. Pediatr Emerg Care. 2013;29(1):71-73.

6. Luu JL, Wendtland CL, Gross MF, et al. Three percent saline administration during pediatric critical care transport. Pediatr Emerg Care. 2011; 17(12):1113-1117.

7. Wang J, Fang Y, Subhashini R, et al. Intraosseous administration of 23.4% NaCl for Treatment of Intracranial Hypertension. Neurocrit Care. 2019;30(2):364-371.

8. Wu AG, Samadani U, Slusher TM, Zhang L, Kiragu AW. 23.4% Hypertonic Saline and Intracranial Pressure in Severe Traumatic Brain Injury Among Children: A 10-Year Retrospective Analysis. Pediatr Crit Care Med. 2019;20(5):466-473. doi:10.1097/PCC.0000000000001867

9. Webster DL, Fei L, Falcone RA, Kaplan JM. Higher-volume hypertonic saline and increased thrombotic risk in pediatric traumatic brain injury. J Crit Care. 2015;30(6):1267-1271. doi:10.1016/j.jcrc.2015.07.022

10.Ayus JC, Caputo D, Bazerque F, Heguilen R, Gonzalez CD, Moritz ML. Treatment of hyponatremic encephalopathy with a 3% sodium chloride protocol: a case series. Am J Kidney Dis. 2015;65(3):435-442

References

11.Dillon RC, Merchan C, Altshuler D, Papadopoulos J. Incidence of adverse events during peripheral administration of sodium chloride 3%. J Intensive Care Med. 2018;33(1):48-53.

12.Farrokh S, Cho SM, Lefebvre AT, et al. Use of intraosseous hypertonic saline in critically ill patients. J Vasc Access.2019;20(4):427-432.

13.Griffin M, Soufer A, Goljo E, et al. Real World Use of Hypertonic Saline in Refractory Acute Decompensated Heart Failure: A U.S. Center's Experience. JACC Heart Fail. 2020;8(3):199-208. doi:10.1016/j.jchf.2019.10.012

14.Jones GM, Bode L, Riha H, Erdman MJ. Safety of continuous peripheral infusion of 3% sodium chloride solution in neurocritical care patients. Am J Crit Care. 2017;26(1):37-42.

15.Lawson T, Hussein O, Nasir M, Hinduja A, Torbey MT. Intraosseous administration of hypertonic saline in acute brain-injured patients: a prospective case series and literature review. Neurologist. 2019;24(6):176-179.

16.Meng L, Nguyen CM, Patel S, Mlynash M, Caulfield AF. Association between continuous peripheral i.v. infusion of 3% sodium chloride injection and phlebitis in adults. Am J Health-Syst Pharm. 2018;75(5):284-291.

17.Mesghali E, Fitter S, Bahjri K, Moussavi K. Safety of peripheral line administration of 3% hypertonic saline and mannitol in the emergency department. J Emerg Med. 2019;56(4):431-436.

18.Perez CA, Figueroa SA. Complication rates of 3% hypertonic saline infusion through peripheral intravenous access. J Neurosci Nurs. 2017;49(3):191-195.

19.Siddiqui EU, Waheed S, Perveen F, et al. Clinical outcome of paediatric patients with traumatic brain injury (TBI) receiving 3% hypertonic saline (HTS) in the emergency room of a tertiary care hospital. J Pak Med Assoc. 2019;69(11):1741-1745. doi:10.5455/JPMA.296439.

20.Sood L, Sterns RH, Hix JK, Silver SM, Chen L. Hypertonic saline and desmopressin: a simple strategy for safe correction of severe hyponatremia. Am J Kidney Dis. 2013;61(4):571-578.