Lining Up to Infuse Excellence Subcutaneous Route for Drugs and
Fluids Annette O. Arthur PharmD Department of Emergency Medicine
University of Oklahoma School of Community Medicine
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Lining Up to Infuse Excellence Disclosures Co-investigator on a
study funded by Halozyme Therapeutics, the manufacturer of the FDA
approved human recombinant hyaluronidase (Hylenex). The
manufacturer had no control over the study design or reporting
content.
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Lining Up to Infuse Excellence Objectives 1.Compare the
pharmacokinetics of IV, IM and SC administration of fluids and
medications 2.Discuss the emerging methods of SC infusion 3.Discuss
proper SC technique
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Lining Up to Infuse Excellence Contents Introduction
Pharmacokinetics Therapies Historical uses Emerging uses SC access
technique Advantages/Limitations
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Lining Up to Infuse Excellence Intravenous (IV) Intramuscular
(IM) Intraosseous (IO) Subcutaneous (SC) Introduction: Parenteral
Routes
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Lining Up to Infuse Excellence Introduction: Hypodermoclysis
Old term for Subcutaneous (SC) fluid infusion Common in early to
mid 1900s Interstitial matrix a barrier to diffusion Adverse events
with hypertonic solutions Development of modern IV catheter
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Lining Up to Infuse Excellence Introduction: Skin
Structure
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Lining Up to Infuse Excellence Introduction: Extracellular
matrix Located in the hypodermis Maintains architecture and
controls fluid flow Collagen fibrils and elastin structure
Viscoelastic gel fluid flow - Glycosaminoglycans -Hyaluronic Acid
Limits SC injection to no more than 2mls Tissue distortion
Increases injection pressure
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Lining Up to Infuse Excellence Introduction: Hyaluronidase
Found in nature to increase the dispersion of substances (sperm,
toxins, venoms, bacteria) Initially derived from bovine testes Use
traced back to 1928 Many impurities leading to increased capillary
permeability and allergic reactions Human recombinant hyaluronidase
HRH FDA approved 2005
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Lining Up to Infuse Excellence Introduction: Hyaluronidase
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Lining Up to Infuse Excellence Introduction: Hyaluronidase HRH
Facilitated Drug Therapy 1.Dexamethasone 2.Famotidine
3.Glycopyrrolate 4.Haloperidol 5.Hydromorphone 6.Lidocaine
7.Magnesium 8.Midazolam 9.Ondansetron 10.Potassium
11.Sufentanil
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Lining Up to Infuse Excellence Pharmacokinetics: Terms C max -
maximum concentration T max time to maximum concentration t 1/2
elimination half-life AUC Area under the serum concentration-time
curve Bioavailability (F) the proportion of drug absorbed into the
circulation and available for physiologic action
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Lining Up to Infuse Excellence Pharmacokinetics: IM vs SC
Similarity in the absorption and efficacy between IM and SC
administration C max AUC T max t 1/2 IM may have variable
absorption depending on blood flow and muscle mass IM absorption is
unpredictable in infants Insufficient muscle tone Insufficient
vascularity
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Lining Up to Infuse Excellence C max Higher IV than SC T max
Faster IV than SC AUC IV and SC similar t 1/2 IV and SC similar
Bioavailability SC injected meds are generally Pharmacokinetics: IV
vs SC
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Lining Up to Infuse Excellence Pharmacokinetics Time (hrs)
Concentration (mcg/ml) IV SC
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Lining Up to Infuse Excellence Pharmacokinetics: SC with HRH C
max Increased T max Faster AUC Increased Bioavailability Increased
Moves SC PKs closer to IV
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Lining Up to Infuse Excellence Pharmacokinetics: SC with
HRH
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Lining Up to Infuse Excellence Therapies: Historical uses
Pediatric rehydration Palliative care (fluids and pain meds)
Deferoxamine Iron chelating agent Haemochromatosis Pts/caregivers
start SC access and administer med w/ ambulatory pump over 8-10
hours 5-7 days/wk
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Lining Up to Infuse Excellence Therapies: Emerging mAbs
Trastuzumab 1998 FDA approved HER2+ breast cancer, early and
metastatic HannaH study, 2012, Ismael et al Wynne et al study, 2013
PrefHer, 2013, Pivot et al Rituximab 2006 FDA approved Targets
CD20; indicated for non-Hodgkins lymphoma and chronic lymphocytic
leukemia SABRINA study, 2013, Davies et al
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Lining Up to Infuse Excellence Therapies: Emerging ABX
Ceftriaxone Third-generation cephalosporin Broad spectrum; gram (-)
and gram (+) activity Once daily dosing Typically administered IV
or IM IV more costly, inconvenient (hospital or Dr. visit) IM
costly, inconvenient, and painful Study published in 2010, Harb et
al Safety and PKs of IV & SC SC w/ HRH and without
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Lining Up to Infuse Excellence Therapies: Emerging ABX, cont.
Ertapenem Long-acting, parenteral carbapenem Mainly indicated for
community/hospital- acquired infections (not Pseudomonas or
Acinetobactor) Daily dosing, IM or IV administration Study in
France by Frasca, 2010 Compare PKs after 30 min IV & SC
infusions SC did not include HRH
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Lining Up to Infuse Excellence Therapies: Emerging IgG 1952 IgG
replacement Tx first given 1950s 1970s IgG given by IM injection
1980s IV became the most common route 2006 SC formulation FDA
approved 2010 higher concentration SC FDA approved 2013 IgG + HRH
in clinical trials SC IM IV SC
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Lining Up to Infuse Excellence Therapies: Emerging IgG cont.
IGIV monthly infusions IGSC weekly home infusions, multiple sites
IGHy monthly infusions, single site, at home Wasserman study, 2012
IGHy bioequivalent to IGIV Main AE with IGHy local Systemic AE IGIV
(25%) > IGHy (8.3%) HA, fatigue, n/v, fever, chills
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Lining Up to Infuse Excellence Therapies: Emerging Pain Mngt
Morphine Sulfate Moderate to severe pain Pt controlled analgesia
(PCA) SC vs IV INFUSE Morphine study, Thomas et al SC Morphine +
Ketoprofen Moselli et al, 2010 Continuous SC MS w/w/o Ketoprofen
for cancer pain
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Lining Up to Infuse Excellence Therapies: Emerging Anti-Emetic
Ondansetron Selective serotonin-blocking agent IM, IV, PO formulas
Approved for n/v Study of SC use in Pregnancy (Klauser, 2011) AEs
mild and transient PKs similar to other discussed drugs
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Lining Up to Infuse Excellence Therapies: Emerging Hydration
Pediatric ORT is first line treatment for dehydration 15% - 20%
unable to perform ORT SC + HRH infusion of fluids safe &
effective SC + HRH more cost-effective than IV Adult Most studies
were conducted in the 1980s- 1990s Studies in 2005 and 2 in 2007
SC+HRH is safe, well-tolerated, and cost effective
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Lining Up to Infuse Excellence Therapies: Emerging Insulin
Hompesch, 2011 Type 1 diabetes mellitus patients Prandial insulins
- Lispro & Regular human insulin Peak exposure incd 35% and 66%
with HRH Time to peak decd significantly Morrow, 2013 Healthy
volunteers HRH + lispro/aspart/glulisine insulins
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Lining Up to Infuse Excellence Therapies: Mass Casualty Events
Ease of SC access Minimal training required; no special equipment
Adverse conditions in the field Poor lighting, cramped spaces,
moving vehicles # Pts > # medical providers MCI injuries often
require quick fluids/meds A variety of injuries and illnesses Crush
injuries
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Lining Up to Infuse Excellence Case report: Severe Hemorrhage
57-yr old lady, with secondary progressive MS ED weakness, clammy,
fever Dx right basal pneumonia Tx IV Abx, fluids, prophylactic LMWH
Swallow assessment signs of silent aspiration Oral feedings unable
to maintain hydration SC fluid infusion replace fluids Day 30
started bleeding at site Pt died 7 hours later
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Lining Up to Infuse Excellence 1.Choose site, prep skin, pinch
2.Insert IV cath (22-24 g); 45 angle 3.Secure catheter with
tape/transparent drsg 4.if using Inject HRH, 150 units/1 ml
5.Attach Standard IV tubing & secure 6.Begin to infuse fluids
a/o meds 7.Rate gravity driven 8.Dont be surprised by some soft
swelling at the site of the infusion; this is normal Technique:
Overview
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Lining Up to Infuse Excellence Technique: Locations
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Lining Up to Infuse Excellence Technique: Skin pinch
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Lining Up to Infuse Excellence Technique: Skin pinch
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Lining Up to Infuse Excellence Technique: Skin pinch,
cont.
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Lining Up to Infuse Excellence Technique: Catheter
placement
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Lining Up to Infuse Excellence Technique: Catheter
placement
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Lining Up to Infuse Excellence Technique: Secure catheter
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Lining Up to Infuse Excellence Advantages: SC vs IV/IM
1.Smaller needle/IV catheter 2.Less pain 3.More sites for
injection/infusion 4.Less frequent site change 5.Avoids infusion
reactions 6.Systemic infection, less concern 7.Administration at
home 8.Less cost
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Lining Up to Infuse Excellence Limitations: SC vs IV/IM
1.Limited volume (1-2mls) 2.Drug trapping 3.Irritants 4.Retention
5.Home administration
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Lining Up to Infuse Excellence Current studies Psoriasis Asthma
Osteoporosis Crohns Dz RA Breast Cancer Hodgkins lymphoma CLL
Multiple sclerosis Alzheimers Dz Pain management Diabetic kidney Dz
Bone healing SLE TTP Etc.
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Lining Up to Infuse Excellence Conclusion Hypodermoclysis has
been used for many decades Pharmacokinetics are well understood
Bioavailability similar to IV administration HRH co-administration
improves PK Uses: fluid resuscitation, mAbs, ABXs, IgG replacement,
insulin, pain management, anti-emetics, and MCI Simple technique
Advantages/disadvantages