Transcript Document

Comparison of preparation of infusion bags on the ward or in
the pharmacy
C Anton1, N Langford1, CJ Poole2, PA Routledge3, A Hutchings3, DN Bateman4, T Sheehan5 , RE Ferner1
1. West Midlands Centre for Adverse Drug Reaction Reporting, City Hospital, Birmingham B18 7QH
2. Regional Cancer Centre, Queen Elizabeth Hospital, Birmingham B15 2TH
3. University of Wales College of Medicine Therapeutics and Toxicology Centre Llandough Hospital, Cardiff CF64 2XX
4. Scottish Poisons Information Bureau, Royal Infirmary of Edinburgh, Edinburgh EH3 9YW
5. Regional Toxicology laboratory, City Hospital, Birmingham B18 7QH
Background
The study of errors is difficult.1 Many previous studies have been observational. We wished to circumvent some of the difficulties of
previous studies, and also to distinguish between random variation in making up solutions and systematic errors in calculation. We
previously used acetylcysteine infusion, used to treat paracetamol poisoning.2 We now examine carboplatin, used to treat cancer.
Acetylcysteine bags are made up on the ward by staff who are not used to making up infusions, whereas carboplatin is made up by trained
pharmacy staff in controlled and sterile conditions Both these drugs are stable and easily assayed. Carboplatin along with other cytoxics
has a low therapeutic index and is usually used close to the maximum tolerated dose.The systematic and random variation in infused drug
doses was not well known before our acetylcysteine study and we had expected it to be very small.
Method
In both experiments the procedure used to collect samples was:
• infusion bag made up by staff in the usual manner
• bag agitated to ensure mixing
• a small sample removed by the ward nursing staff and stored in the
fridge and labelled with patient’s height and weight, pre- or postinfusion sample and patient identifier
• after infusion a further small sample is removed (if possible) and
stored as above
• batches sent for analysis weekly
The acetylcysteine samples were collected in 4 centres in the UK
between August and October 1999. The carboplatin samples were
collected in 1 centre between July and December 2003.
Results
We calculated the results as a percentage of the anticipated
concentration of the drug in the bag. For example, if the bag
contained only half of the expected amount of the drug intended by
the prescriber our result would be 50%. The cumulative distribution of
the results we found in 187 bags of acetylcysteine and 53 bags of
carboplatin are shown in the Figure and Table. The median
concentration of the bags was
1.0
0.9
0.8
proportion of observations
Carboplatin was analysed by plasma ionization mass spectrometry,
and acetylcysteine was analysed by HPLC.
Cumulative frequency distribution of acetylcysteine and carboplatin infusion bags
0.7
0.6
0.5
0.4
0.3
0.2
acetylcysteine
0.1
carboplatin
0.0
50
60
70
80
• acetylcysteine 101.1% (interquartile range, 88.5% – 117.0%)
• carboplatin
90
100
110
120
130
140
150
% anticipated dose
99.4% (97.8% – 101.9%)
Discussion
We thought most patients would receive within about
10% of the anticipated dose, but in the acetylcysteine
samples made up on the ward only one third did; and
one third differed by more than 20% from the anticipated
dose. Some 9% were wrong by a factor of 2 or more.
Parshuram and colleagues have recently published
similar alarming results for opiate infusions in children.3
All the carboplatin bags were within 10% of the
anticipated dose and over 80% were within 5% of the
anticipated dose. A previous
study detected a wide inter-patient variation in the
maximum tolerated dose of carboplatin, and
hypothesized that dose delivery errors were a potential
explanation.4 Our audit shows that the upper 95%
confidence limit for the major error rate is 3/53 (6%). We
conclude, that in critical cases where under- or overdosage would be serious, infusion bags should be made
up by experienced pharmacy staff under controlled
conditions and not on the wards
References
1. Ferner RE, Aronson JK. Errors in prescribing, preparing, and giving medicines: definition, classification, and prevention. In: Side effects of drugs annual. 22nd edn. (Ed:
Aronson,JK). Elsevier Science Ltd., Amsterdam, 1999: xxiii-xxxvi.
2. Ferner RE, Langford NJ, Anton C, Hutchings A, Bateman DN, Routledge PA. Random and systematic medication errors in routine clinical practice: a multicentre study of
infusions, using acetylcysteine as an example. Br. J. Clin. Pharmacol. 2001; 52: 573-7.
3. Parshuram CS, Ng GY, Ho TK, Klein J, Moore AM, Bohn D, Koren G. Discrepancies between ordered and delivered concentrations of opiate infusions in critical care. Crit.
Care Med. 2003; 31: 2483-7.
4. Jordan SD, Poole CJ, Archer VR, Steven NM, Burton A. A retrospective evaluation of the feasibility of intrapatient dose escalation as appropriate methodology for doseranging studies for combination cytotoxic regimens. Cancer Chemother Pharmacol. 2003; 52: 113-8.
No of bags
Minimum concent rat ion*
Maximum concent rat ion
No of bags w it hin 5% of
int ended concent rat ion
(proport ion)
No of bags w it hin 10% of
int ended concent rat ion
(proport ion)
No of bags w it hin 50% of
int ended concent rat ion
(proport ion)
acetylcysteine
187
carboplatin
53
51%
91%
305%
105%
36 (0.19)
43 (0.81)
69 (0.37)
53 (1.0)
169 (0.9)
53 (1.0)
* 1 of the acetylcysteine bags contained no measurable acetylcysteine. We
attributed this to a protocol error where the sample was taken before the
acetylcysteine was injected into the bag