WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

Nagaraju et al. SJIF Sciences

World Journal of Pharmacy and Pharmaceutical Impact Factor 5.210

Volume 4, Issue 08, 1227-1237. Research Article ISSN 2278 – 4357

ASSESSMENT OF INTRAVENOUS ADMIXTURES

INCOMPATIBILITIES & THE INCIDENCE OF INTRAVENOUS DRUG
ADMINISTRATION ERRORS

A. Nagaraju*& A. Samson Deepak1, C. Aruna& K. Swathi1, Purushothama Reddy.K2,

Dr. Sri Devi.K3, Dr. M.Purushothaman4

1
Pharm.D Interns, Department of Pharmacy Practice, P. Rami Reddy Memorial College of
Pharmacy, Kadapa, India.
2
Assistant Professor, P. Rami Reddy Memorial College of Pharmacy, Kadapa, India.
3
Associate Professor & I/c HOD, Department of Pharmacology, RIMS, Kadapa, India.
4
Principal of P. Rami Reddy Memorial College of Pharmacy, Kadapa, India.

Article Received on
ABSTRACT
27 May 2015, Background: Intravenous(IV) admixtures are the preparations consist
Revised on 22 June 2015, of 1or more sterile drug products added to an IV fluid, generally
Accepted on 15 July 2015
Normal saline Solution (0.9% Nacl) or Dextrose (5%) alone or in
combination. Drugs that may cause irritation or toxicity when given as
*Correspondence for
a rapid direct IV injection are also prepared as IV admixtures. Aims &
Author
Objectives: “To assess the potential incompatibilities associated with
Dr. A. Nagaraju
Pharm.D Interns, IV admixtures & the incidence of IV drug administration errors in a
Department of Pharmacy tertiary care teaching hospital”. Materials & Methods: The data for
Practice, P. Rami Reddy the present study was collected by „Chart Review‟ method for a
Memorial College of
period of 6 months. This study included all the hospitalized patients of
Pharmacy, Kadapa, India.
General Medicine. The collected data was analyzed for
incompatibilities by using standard drug reference texts. Results: We found 114
combinations (both Drug-Solute and Drug-Drug combinations) among them 29 (25.43%)
were compatible, 33 (28.94%) incompatible, 8 (7.01%) were variable and 44 (38.59%) were
undocumented combinations. Out of 16 IV drugs administration errors 4 (25%) were found to
be wrong drug preparation errors, 6 (37.5%) were wrong rate of administration, 2 (12.5%)
were wrong time errors and 4 (25%) were omission errors. Conclusion: Our study concluded
that this type of research work would certainly increases the safety in the use of IV
admixtures. It is important to make health care professionals to aware of compatibility

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problems, daily prescription review by clinical pharmacist and providing unbiased

information from reliable references could possibly prevent compatibility errors in the wards.

KEYWORDS: Intravenous admixtures, Incompatibilities, Administration errors, Clinical

Pharmacist.

INTRODUCTION
Intravenous admixtures are the preparations consist of 1 or more sterile drug products added
to an IV fluid, generally Normal saline Solution (0.9% Nacl) or Dextrose (5%) alone or in
combination. Drugs that may cause irritation or toxicity when given as a rapid direct IV
injection are also prepared as IV admixtures.[1] These parental drug solutions are commonly
mixed in the same infusion bag, at the Y-site junction where 2 or more IV lines meet and in
the same syringe.[2]

IV incompatibilities occur when 2 are more drugs are administered through a single IV line
or given in a single solution, resulting in an undesirable reaction.[3] A patient who receives a
preparation in which an incompatibility has occurred could experience toxicity or an
incomplete therapeutic effect. There are 3-types of incompatibilities physical, chemical and
therapeutic incompatibilities.[4]

A Physical incompatibility (PI) occurs when a drug combination produces a visible change in
the appearance of a solution.[1] It is also known as “Pharmaceutical Incompatibility or
Visual Incompatibility”.[5] PIs are observed more easily and can be detected by changes in
the appearance of admixture such as change in color, formation of precipitate or evolution of
gas. This renders the solution unsafe for administration.[6]

A Chemical incompatibility (CI) reflects the chemical degradation of 1 or more of the

admixed drugs, resulting in toxicity or therapeutic inactivity.[2] The degradation is not always
visible but the reaction of drug or drugs in solutions which results in alterations in either
integrity or potency of the drug.[7] Non-visible chemical incompatibility may be detected only
by analytical methods.[6]

Large amount of particulate matter in injections is considered as a potential life threatening

health hazard.[8] Drug incompatibility reactions may not only generate particles in the infuse,
but also transform drug into an inactive form and deleterious effects on the patients
prescribed drug regimen.

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Clinical effects of incompatibilities are hypoxia, impairment in discharge of metabolic

products and finally tissue ischemia. These incompatibilities may therefore have most
detrimental effects in patients who suffer from preexisting microcirculatory disorders due to
trauma, major surgery and sepsis etc.[9]

It is prudent not to mix the solutions of parenteral drugs without knowledge of their
compatibility.[2] Information regarding drug incompatibilities are well documented in
computer databases, AHFS etc.,[10,11] and information leaflets published by pharmaceutical
Companys.[12]

The number of IV medications continues to expand and the need to administer different IV
drug combinations are increasing day by day.[13] In general nursing staff prepare and
administer IV medications prescribed by Doctors. Due to increased number of drug
combinations, the knowledge regarding IV drugs is limited. It is not possible to predict all
incompatibilities but the presence of clinical pharmacist in ward, clinical review of possible
incompatibilities may minimize the occurrence and ultimately it increases the patient safety.

METHODS AND MATERIALS

A prospective observational study was conducted for a period of 6 months from November
2013 to April 2014 at Rajiv Gandhi Institute of Medical Sciences (RIMS), a tertiary care
teaching hospital, Kadapa. The study was approved by the Human Research Ethical
committee, RIMS, Kadapa (RC. No.3349/Acad./2013-14/Dated 19-11-2013).

DATA COLLECTION
The data for the present study was collected by “Chart Review Method”, which is well
suited to identify the prescribed drugs for the individual patients. A suitable data collection
form was prepared and utilized to collect the study details. This form mainly contains details
like patients demographics, reasons for hospitalization, drugs and solutes and method of drug
administration. Drug administration data was collected basing on 2 criteria.

a) When a single drug delivered by infusion, the compatibility of drug in solution will be
noted.
b) When 2 or more drugs are used in the same infusion line then drug-drug and drug-solute
compatibilities will be noted.

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This obtained data will be compared with the information available in the following
literatures.
 Drugdex - Drug evaluation monographs in Micromedex 2.0 (Computer drug database).
 AHFS Drug Information text, 2010 & 2011[10,11]
 British National Formulary 57thEdition.[13]
 Trissel’s Handbook of Injectable drugs.[14]
 Published leaflets of Pharmaceutical companies.

RESULTS
1. PART – A: A total of 220 Patients were observed. Out of 165 study population we found
a total of 114 IV drug admixtures combinations, among that:
i. Drug – IV solution Combinations were 16 (14.03%) which includes, based on contact
site (Y – site) 8 were compatible, 2 were incompatible, 1 were variable and 5 were
undocumented.
ii. Drug – Drug Combinations were 98 (85.96%) which includes, based on contact site (Y
– site) 88, i.e., 12 were compatible, 21 were incompatible, 4 were variable, 48 were
undocumented and drugs given through Mixture are 10, i.e., 3 were compatible, 4 were
incompatible and 3 were undocumented.

Table 1: Details on Compatibility of IV drugs administered during the study period;

No. Of Drug – IV No. Of Drug – Drug
Compatibility solution Combinations Combinations
Total (%)
Y – site Mixture Y - site Mixture
Compatible 8 0 18 3 29 (25.43%)
Incompatible 2 0 27 4 33 (28.94%)
Variable 1 0 7 0 8 (7.01%)
Undocumented 5 0 36 3 44 (38.59%)
Total 16 0 88 10 114 (100%)

• The 3 incompatible drug solute combinations are found to be Phenytoin + 0.9% Nacl,
Insulin + DNS and Ceftriaxone + Ringer lactate.
• When Phenytoin is mixed with 0.9% Nacl, visible crystals of Phenytoin get formed
within 10-15 minutes, ultimately leading to physical incompatibility. It is recommended
that Phenytoin injection is not to be mixed with any other solution.
• Insulin is given along with DNS, insulin absorbed to the surface of IV infusion solutions
containers (both glass and plastic container).

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• Ceftriaxone is incompatible with Lactated Ringer’s (RL) solution as the Calcium present
in this solution forms precipitate with ceftriaxone. So, ceftriaxone should not be diluted
with RL’s solution.

Table 2: Details of frequency of Drug-Solute combinations usage;

Drug-Solute combinations Frequency (%) Compatibility
Streptokinase + 0.9% Nacl,
Multivitamin + 0.9% Nacl 3(11.53%)
Theophylline + 0.9% Nacl,
Iron sucrose + 0.9% Nacl 2(7.69%) Compatible
Calcium + 0.9% Nacl,
Dopamine + 0.9% Nacl,
1(3.84%)
Atropine + 0.9% Nacl
Phenytoin + 0.9% Nacl,
2 (7.69%)
Insulin + DNS (5%) Incompatible
Ceftriaxone + Ringer lactate 1(3.84%)
Phenytoin + Dextrose normal saline 1(3.84%) Variable
Diclofenac + 0.9% Nacl,
Hepamerz + Dextrose normal saline 2(7.69%)
Diclofenac + Ringer lactate, Undocumented
Edveran + 0.9% Nacl,
1(3.84%)
N- Acetylcystine + 0.9% Nacl
16 26 (100%) Total

Table 3: Details on frequency of usage of Compatible Drug - Drug Combinations

Drug Compatible drug combinations Frequency
Frequency
Code (n = 21) (%)
1. Pantoprazole + Ceftriaxone 30 28.8%
2. Furosemide + Ceftriaxone 23 13.4%
Pantoprazole + Deriphylline,
3. 12 5.45%
Amikacin + Ranitidine
4. Furosemide + Deriphylline 7 5.53%
Ciprofloxacin+ Metronidazole,
5.
Ceftriaxone + Metronidazole 5 3.92%
Ondansetron + Ranitidine,
6. Dexamethasone + Ondansetron,
4 3.13%
Furosemide + Ranitidine.
Ceftriaxone + Mannitol,
7. 3 2.38
Hydrocortisone + Pipercilintazobactum
Hydrocortisone + Theophylline,
Ranitidine + Furosemide,
8. Ondansetron + Hydrocortisone,
2 1.58%
Pipercilintazobactum + Ondansetron
Deriphylline + Hydrocortisone
Amikacin + Ondansetron,
9. Gentamycin + Metronidazole,
1 0.79
Amikacin + Metronidazole,

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Ceftriaxone + Furosemide
Total 21 126 100%

Table 4: Details on frequency of usage of Incompatible Drug - Drug Combinations

Drug Incompatible Drug – Drug combinations Frequency
Frequency
code (n = 31) (%)
1. Pantoprazole + Furosemide 21 13.11%
2. Amikacin + Pantoprazole 17 10.62%
3. Pantoprazole + Ondansetron 14 8.75%
4. Pantoprazole + Hydrocortisone 12 7.52%
5. Pantoprazole + Pipercilintazobactum 9 5.62%
Pantoprazole + Ciprofloxacin
6.
Diazepam + Pantoprazole 7 4.37%
Cefotaxime + Pantoprazole,
Ciprofloxacin + Ceftriaxone,
Furosemide + Ondansetron,
7.
Phenytoin + Pantoprazole,
6 3.75%
Dexamethasone + Pantoprazole,
Ceftriaxone + Deriphylline
Amoxicillin + Gentamycin,
8. Phenytoin + Diazepam,
5 3.12%
Metronidazole + Pantoprazole.
Atropine + Pantoprazole,
Pantoprazole + Amikacin,
9.
Diazepam + Ceftriaxone, 3 1.87%
Furosemide + Ciprofloxacin
Amikacin + Diclofenac,
10. Phenytoin + Ceftriaxone, 2 1.25%
Atropine + Pantoprazole
Metronidazole + Phenytoin,
Deriphylline + Ondansetron,
Pantoprazole + Ranitidine,
Ofloxacine + Pantoprazole,
11.
Hydrocortisone + Ampicillin,
1 0.62%
Amikacin + Metronidazole,
Phenytoin + Theophylline,
Furosemide + Gentamycin
Total 31 160 100%

Table 5: Details on frequency of usage of Variable Drug - Drug Combinations

Drug code Variable Drug – Drug combinations (n = 7) Frequency Frequency (%)

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1. Furosemide + Hydrocortisone 5 33.33%

2. Pipercilintazobactum + Amikacin 3 20.01%
Mannitol + Pantoprazole,
3. 2 13.3%
Amikacin + Ceftriaxone
Ampicillin + Ranitidine,
4. Ceftriaxone + Theophylline, 1 6.66%
Pantop + Furosemide.
Total 7 15 100%

Table 6: Details on frequency of usage of Undocumented Drug – Drug Combinations

Drug Undocumented Drug – Drug combination Frequency
Frequency
code (n = 50) (%)
1. Augmentin + Pantoprazole 14 11.86%
Ceftriaxone + Ranitidine
2. 11 9.32%
Ceftriaxone + Ondansetron
Augmentin + Deriphylline,
3.
Hydrocortisone + Chlorpheneramine maleate. 9 7.62%
4. Augmentin + Furosemide 7 5.93%
5. Hydrocortisone + Ceftriaxone 6 6.0%
Chlorpheneramine maleate + Pantoprazole,
6. 5
Piracetam + Ceftriaxone 3.30%
7. Mannitol + Piracetam 4 3.41%
Chlorpheneramine maleate + Furosemide,
Piracetam + Furosemide,
8.
Augmentin + Hydrocortisone, 3 2.54%
Augmentin + Ondansetron
Furosemide + Cefotaxime,
9. Dexamethasone + Ceftriaxone, 2 1.69%
Metronidazole + Ondansetron
Augmentin + Ranitidine,
Dicyclomine + Pantoprazole,
Dicyclomine + Ceftriaxone,
Vitamin K + Ceftriaxone,
Vitamin K + Ranitidine,
Vitamin K + Furosemide,
Hydrocortisone + Ranitidine,
Piracetam + Ranitidine,
Augmentin + Ethamsylate,
Deriphylline + Ethamsylate,
10.
Multi vitamin + Pantoprazole,
1 0.84%
Multi vitamin + Hydrocortisone,
Hydrocortisone + Piracetam,
Multi vitamin + Pipercilintazobactum,
Phenytoin + Artesunate,
Ceftriaxone + Artesunate,
Chlorpheneramine malate + Ceftriaxone,
Pipercilintazobactum + Ceftriaxone,
Phenytoin + Cefotaxime,
Piracetam + Diazepam,

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Piracetam + Phenytoin,
Furosemide + Pipercilintazobactum,
Ciprofloxacin + Ondansetron
Total 39 118% 100%

2. PART – B; “IV Medication errors” is defined as any deviation of preparation or

administration of an IV dose from the original prescription or any act in the preparation or
administration, which deviated from the manufacturer’s instructions or the hospital drug
policy.

Frequency of all types of Intravenous drugs administration errors: Out of 16 IV drugs

administration errors 4 (25%) were found to be wrong drug preparation errors, 6 (37.5%)
were wrong rate of administration, 2 (12.5%) were wrong time errors and 4 (25%) were
omission errors.
Table 7: Frequency of all types of Intravenous drugs administration errors
Type of Errors Frequency Frequency (%)
Wrong drug preparation errors 4 25%
Wrong rate of administration 6 37.5%
Wrong time errors 2 12.5%
Omission errors 4 25%
Total errors 16 100%

Table 8: Details on frequency of Wrong Drug Preparation Errors

No. Of Wrong drug Frequency Frequency
Name of the drugs
preparation errors (n=23) (%)
1 Ranitidine 8 34.78 %
2 Pantoprazole 7 30.43 %
3 Ceftriaxone 5 21.73 %
4 Pipercilintazobactum 3 13.04 %
Total 4 23 100 %

Table 9: Details on frequency of Wrong Rate of Administration Errors

No. Of Wrong Rate Frequency
Name of the drugs Frequency (%)
Administration Error (n = 73)
1. Ceftriaxone 23 31.50%
2. Pantoprazole 17 23.28%
3. Furosemide 13 17.80%
4. Ondansetron 11 15.06%
5. Hydrocortisone 6 8.21%
6. Amikacin 3 4.10%
Total 6 73 100%
Table 10: Details on frequency of Wrong Time Errors
No. of Wrong Name of the drugs Frequency Frequency

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Time Errors (n=4) (%)

1. Augmentin 3 75%
2. Diazepam 1 25%
Total 2 4 100%

Table 11: Details on frequency of Omission Errors

No. of Omission Frequency Frequency
Name of the drugs
Errors (n=7) (%)
1. Ceftriaxone 4 57.12%
2. Pantoprazole 1 14.28%
3. Furosemide 1 14.28%
4. Ondansetron 1 14.28%
Total 4 7 100%

DISCUSSION
The preparation and administration of IV admixtures are associated with considerable risks
and 1 of the risk is physicochemical incompatibilities. Nursing staff doesn’t have enough
knowledge regarding the compatibilities of the drugs and so, clinical pharmacist can may not
prevent but minimize the incidence of such type of reactions. “Rajeev Gandhi Institute of
Medical Sciences” (RIMS), is a 750 bedded tertiary care teaching hospital situated in
Kadapa, there was no studies conducted previously in this rural hospital regarding assessment
of IV admixtures in hospitalized patients. Such a study could provide valuable information to
the physicians and nursing staff regarding to the safe usage of IV admixtures.

The study mainly focuses on compatibility of Drug-Solute 16 (14.03%) and Drug-Drug

combinations 98 (85.96%). This study showed that out of 114 combinations (both Drug-
Solute and Drug-Drug combinations), 29 (25.43%) were compatible, 33 (28.94%)
incompatible, 8 (7.01%) were variable and 44 (38.59%) were undocumented combinations.
This is similar to the study conducted by K.V. Ramanathet al.,[10] and Celine Serrurieret
al.,[15] in which undocumented combinations were more when compared to compatible and
incompatible combinations. This result is contrast to the studies conducted by M. Gikicet
al.,[4] Humbert – Delaloye Valiaet al.,[16] in which compatible combinations were more when
compared to incompatible and undocumented combinations. The incompatibility problem
should be considered seriously for better therapeutic outcomes.

Limitations of the Study: There are two major limitations for the present study. Firstly, data
collection was done only during day time. Secondly, the duration of the study was small and

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most frequently used drugs in General Medicine were included. But rare drugs which are
highly potential for incompatibilities were not included in the study.

CONCLUSION
Our study concluded that research work would certainly increase the safety in the use of IV
admixtures. It is very important to make nurses aware of compatibility problems. Some
incompatibilities are eminently predictable from simple chemical knowledge, but most
compatibilities and incompatibilities are not easily predicted. For this reason, the decision to
mix any 2 injection solutions whether in syringe, infusion bag or at Y – site should be based
on reliable references.

Given the importance of compatibility of IV medication admixtures a compatibility chart and

drug information leaflet for frequently used drugs was prepared and placed in wards which
mainly helps to reduce IV incompatibilities especially when there is a need to mixing drugs
together. A daily prescription review by pharmacist could possibly prevent compatibility
errors found on the wards.

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