Stopper fragments in parenteral preparations: a potential problem

4 College of Nursing, University of São Paulo at Ribeirão Preto, Department of Fundamental Nursing. Ribeirão Preto, São Paulo, Brazil. ABSTRACT Introduction: The presence of extrinsic particles in injectable solutions is a medication error of usual occurrence that may has important clinical significance. This study aimed to evaluate the presence of stopper fragments in solution derived from bottle-vial after the preparation of drugs using different sorts of needles. Outline: experimental study, wherein 50 bottles-vials were used, divided into groups. Group 1: stopper perforated with three-bevel tip needle; Group 2: stopper perforated with blunt tip needle; Group 3: without perforation of the stopper. The figure and the size of the particles were determined through optic microscopy. The data were analyzed by means of descriptive statistics and the differences among the groups were analyzed through Fischer’s Exact Test. Results: it was verified the presence of six stopper fragments in the solution derived from five bottles which had the stoppers perforated by three-bevel tip needle (29.4%) and the two fragments in two bottles which had the stoppers perforated with blunt tip needle (11.8%), with significant difference (p=0.044) in the comparison among the groups. The three-bevel tip needle produces larger particles (0.36 mm2) than then blunt tip needle (0.12mm2). Implications: risk evaluations must enable the limitation, the detection, and the rejection of atypical unities at the time of the drugs’ preparations, preserving patient safety.


INTRODUCTION
The pharmacovigilance is the set of activities of detection, evaluation, comprehension and prevention of Adverse Events associated with the use of Drugs (AED), in order to ensure patient's protection and to promote information to the health professionals, favoring the rational use of medicaments, screening and preventing either potential or real Medication Errors (ME). [1][2] The ME is any avoidable event that can lead to the inappropriate use of medicaments or bring about harm to a patient, while the drug is under the control of the health professionals, patients or consumer.
This event can be related with the professional practice or with the products, procedures and adopted systems. [2][3] In this light, it is highlighted the phenomenon known in the international literature as coring, [4][5] which characterizes a ME that involves the involuntary presence of extraneous, movable and undissolved particles in the solution contained, for instance, in shots or inoculations to be administred. 6 Such presence of particulate material in parenteral products is a complex subject matter, but the occurrence is habitual, ranging from 3.1% to 97%. The increased variation in the frequency can stems from the detection method applied, from the quality and kind of the studies supplies, multiplicity of use and the angle of insertion of the needles in the bottles' stoppers. 7 Depending on the route of administration, on the size, composition and number of injected particles, as well as the characteristics of the patient, the clinical events associated with the injection of the particle or strange body in the organism at the time of parenteral administration of drugs can be either acute or chronic. They include phlebitis, pulmonary embolism, neurological sequelae of paradoxical embolism, granuloma, immune system dysfunction, myocardial infarction, anaphylaxis in patients with hypersensitivity to latex and death. [8][9] However, the clinical significance and the microembolic consequences of accidental injection of undesirable fragments have not yet been enough know and described, may be underestimated and underreported, possibly due to the difficulty of immediate detection of the event. 4 The presence of particles in injectable drugs can assume two classifications, based on the source of the particulate matter: intrinsic particles (originally associated with the solution) and extrinsic particles (that enter either in the container or in the solution). The general sources of such particles include the environment, the packaging, the components of the formulation, the interaction between product and packaging, and the ones caused by process. For instance, it has already been suggested that the refrigeration of the bottles of medication raises the incidence of microscopic fragments of rubber in the lumen of the needle before the shot due the change of the physical properties of the rubber stopper. 10 In its turn, the Brazilian Health Regulatory Agency (ANVISA), ranks the matter foreign to the drug into three types: parts of the organisms from which the drug derives above of the specified tolerance limit; any organisms, portions or products of organisms beyond the ones specified in the definition and description of the drug; impurities of mineral or organic nature, not inherent to the drug. 11 The event can be minimized by the visual inspection of the presence of particles by the professional, but this evaluation is easily impaired by factors as: tiny size of the particles; situation in which the drug was diluted; reduced luminosity in the ambient; quality of the eyesight of the drug administrator; drug's coloration; place where the fragment is housed in the needle or in the vial; lack of knowledge of the drug administrator. 12 The supplies employed in the preparation of injectable drugs can also contribute for the occurrence of contamination by atypical unities. A study mentioned the presence of stopper fragments sizing 0.4x1.5 millimeters (mm) obstructing the light of a flexible catheter, during the intravenous administration of anesthetic. For the researchers, the embolization was only avoided because the catheter had a reduced lumen. Posterior tests indicated that bodies of rubber fragments in bottles of the same anesthetic were detected when utilized cannulae without cut for the aspiration, but not when utilizing sharp 20 Gauges or 18 Gauges (G) needles, so that the researchers did not recommend the use of cannulae without cut for the aspiration of drugs. 13 Based on the principle of that the strength required to perforate a rubber stopper with the needle depends on the perforating angle, other studious ones determined the incidence of fragments after puncture of anesthetic vials' stoppers, with short chamfered and sharp needles, by two different angles (approximately 90º and 45º) and identified significant reduction of 47.8% in the event when the angular puncture technique was used. 14 Other authors and the pharmaceutical industry itself recommend the use of aspiration needles without cut and/or with filter for the same purpose, although the literature still lacks studies on this thematic. It was observed that needles with filter can make the aspiration process to happen slowly and to favor the formation of air bubbles, making it difficult their use in practice. 4,14 For Lehr et al. 15 , the contamination of Fischer's Exact Test. In all analyses, the significance level of 5% (p < 0.05) was adopted. Table 1 shows the results regarding the presence of rubber particles in the bottles of the intervention groups (Groups 1 and 2) and control group (Group 3) after the experiment.
design, analysis and interpretation of the results and manuscript's writing. All the authors agree and take responsibility for the content of this manuscript version to be published.

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CONFLICTS OF INTEREST
There are no conflicts of interest to declare.