Hospital Pharmacy - December 2017 - 766

738510
research-article2017

HPXXXX10.1177/0018578717738510Hospital PharmacyPereira et al.

Article

Production Standard and Stability of
Compounded Del Nido Cardioplegia
Solution

Hospital Pharmacy
2017, Vol. 52(11) 766-773
© The Author(s) 2017
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https://doi.org/10.1177/0018578717738510
DOI: 10.1177/0018578717738510
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Luis M. Pereira1, Gregory S. Matte2, Peter Lutz3,
Alana Arnold3, and Al Patterson3

Abstract
Background: The del Nido cardioplegia solution (dNCS) was originally developed for pediatric cardiac surgery, being now also
used for adult patients. Hospital pharmacies frequently resort to internal dNCS production which has led to an increase in the
need for validated parameters for compounding and storage. Objective: This report defines in-house production standards,
as well as the stability of dNCS under optimal storage conditions. Methods: All ingredients were sterile and United States
Pharmacopeia (USP)/National Formulary (NF) certified. All final bags were quarantined at 4°C for quality control, when 3 of 33
weekly bags were randomly assayed for potassium content. Each lot was only released if all 3 samples were within ±5% of target.
Stability testing was performed per USP 797 guidance. Over a 6-month period, 4 different lots and 4 bags from each lot of dNCS
were assayed. Each bag was assessed for physical and chemical stability while refrigerated at 4°C, at 35°C in an incubator, and
at 70°C under 80% relative humidity. A light exposure arm was also set up at 25°C under 150 lumens. Calibrators of lidocaine,
mannitol, and gluconate were freshly prepared and assayed with the samples by Liquid chromatography/Mass spectrometry (LC/
MS). Results: Lidocaine concentrations averaged 0.117 mg/mL (95.8% of theoretical) at 4°C for 30 days. At 35°C, they decayed
by 67% in 30 days, while at 70°C nearly 50% was lost after the first day. A first-order kinetics was observed with an Arrhenius
activation energy of 25 kcal/mol. Degradation products identified under stress conditions were absent in the stable product.
Conclusions: The dNCS is stable for at least 30 days under 4°C refrigeration in ethylene vinyl acetate (EVA) bags.
Keywords
del Nido cardioplegia, cardiac surgery, sterile products compounding, hospital pharmacy, cardioplegia additive stability

Introduction
An ideal cardioplegia solution affords safe and sustained
electromechanical cardiac quiescence during cardiac surgery
when the heart must be stopped. It must also provide a stable
arrest while minimizing electrolyte shifts across the myocardial cell membrane, particularly for calcium, avoiding
adverse effects once the heart is reperfused. Due to stability
issues and individual physician preferences, hospital
pharmacies often compound complex sterile solutions such
as del Nido cardioplegia solution (dNCS). This practice is
not without risk1 and strict state and federal compounding
guidelines have been generated over the years.
In the 1990s, the del Nido cardioplegia formula was
developed for use in infants and children undergoing cardiac
surgery.2 By using hypothermia and specific additives in the
solution, cardioplegic arrest is able to induce a reduction in
myocardial energy consumption.3,4 The usage of the dNCS
has been common practice in pediatric cardiac surgery for
decades now,2 with literature reports comparing it against
institutional standard multidose cardioplegia protocols.5,6
The use of dNCS in adult cardiac surgery has increased too

over the last several years, driven by its safety and efficacy3,7
despite limited animal experimentation and controlled trials
in adult cardiac surgery patients. Early reports of del Nido
cardioplegia in adult cardiac surgery are encouraging with
less interventions required by the surgeon owing to longer
intervals between cardioplegia redosing and improved glucose management with decreased postoperative insulin
requirements.8
The widespread and increasing use of dNCS necessitates
formal and validated compounding methods. Stability
1

PKLab at Boston Children's Hospital, Department of Anesthesiology,
Perioperative and Pain Medicine, Harvard Medical School, Boston, MA,
USA
2
Department of Cardiac Surgery, Boston Children's Hospital, Boston, MA,
USA
3
Department of Pharmacy, Boston Children's Hospital, Boston, MA, USA
Corresponding Author:
Luis M. Pereira, Department of Anesthesiology, Perioperative and Pain
Medicine, PKLab at Boston Children's Hospital, Harvard Medical School,
300 Longwood Ave, Boston, MA 02115-5724, USA.
Email: luis.pereira@childrens.harvard.edu

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