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--4 A and plastic intravenous fluid hags, J Am Med Assoc 223:328 (Jan l!i) 1973. 30. Nedich HI.: Vitamin A absorption from plastic iv bags, J Am Med Aism 224:1531-1532 (Jun 11) 1973. 31. Chiou WL and Moorhatch P: beaching of chemicals from plastic intravenous fluid bags, J Am Med Assoc 224:1298-1299 (May 28) 1973. 32. Weisenfeld D, Podolsky S, Goldsmith L et al: Adsorption of insulin to infusion bottles and tubing. Diabetes 77:766-771 (Dec) 1968. 33. Petty C and Cunningham NL: Insulin adsorption by glass infusion bottles, polyvinylchloride infusion containers, and intra venous tubing. Anesthesiology 40:400-404 (Apr) 1974. 34. Autian J: Toxicity and health threats of phthalale esters: review of the literature. Environ Health Ferspect 3:3-26 (Jun) 1973. 35. Rubin RJ and Jaeger RJ: Some pharmacologic and toxicologic effects of di-2-ethylhexyl phlhalate (DEHP) and other plasticizers. Environ Health Ferspect 3:53-59 (Jan) 1973. 36. Anon: PVC, plasticizers and the pediatrician. Lancet 1172-1173 (May 24) 1975. 37. Singh AR, I^twrence WH and Autian J: Mutagenic and a tifertility sensitivities of mice to di-2-ethylhexyl phthalate (DEH and dimethoxyethyl phthalate (DMEP), Toxicol Appl Pharmac 29:35-46,1974. 38. Singh AR, Lawrence WH and Autian'J: Maternal-fet transfer of NC-di-2-ethylhexyl phthalate and ,4C-diethyi phthala in rats,./ Fharm Sci 64:1347-1350 (Aug) 1975. 39. Wallin RF, Klamer B, Nicora RW et al: Di(2-ethylhexyl phthalate (DEHP) metabolism in animals and post-transfusk tissue levels in man. Bull Parenter Drug Assoc 28:278-287 (No' Dec) 1974. 40. Jacobson MS, Kevy SV and Grand RJ: Effects upon t) subhuman primate of a plasticizer leached from polyvinyl chlorid a consequence of chronic transfusion therapy, to be published in Lab Clin Med. Am J Hosp Pharm 34:362-386 (Apr)19 Hazards of mechanical ventilation--therapeutic implications David M. Angaran, Randal L. Wise and Marvin L. Birnbaum The side effects and adverse reactions associated with the use of positive pressure volume cycle ventilators are described with a focus on information the pharmacist needs to know to monitor patient drug therapy. Mechanical ventilation is discussed with regard to pulmonary and blood gases, infections, cardiovascular effects, renal-fluid status, metabolic considerations, central nervous system ef fects, gastrointestinal effects, musculo-skeletal reactions, discontinuance of mechanical venti lation and the use of inhalation drugs. Key Words: Equipment; Inhalation therapy. Pharmacists, hospital; Toxicity - The intent of this article is to review a nondrug treat ment--mechanical ventilation--which has grown in im portance, sophistication and frequency in the last 10 years. The introduction of the volume cycle positive pressureventilator has significantly changed the treatment of res piratory failure. While bringing life to some patients, it has also been controversial in its ability to prolong life. The pharmacist must realize that a ventilator is like a drug. This "drug" is involved with the lungs, oxygen and carbon dioxide components of body physiology. Alteration of oxygen and carbon dioxide concentrations may be ther apeutic or dangerous (side effects). Positive pressure ven tilation also produces changes in body physiology that are independent of blood gas alterations (adverse reactions). Ventilators work by either forcing air into the lungs (positive pressure) or creating a negative (subatmospheric) pressure around the thorax and letting normal intrathoracic Dmvid M. Angarao, M.&, is Assistant Professor, College of Pharmacy, University of Minnesota, Minneapolis SS4I4. Randal L. Wise ia a Certified Respiratory Therapy Technician, University of Wisconsin Hospitals, Mad* tson; and Marvin L. BiraImam, M.D,, b Associate Professor of Medicine and Physiology, and Director of Emergency Medical Services Program, University of Wisconsin Hospitals. pressure expand the lungs. The classic negative pressur ventilator is the "iron lung." Positive pressure machines require that the patient hav an artificial airway (endotracheal or tracheostomy) in plac for use. The negative pressure machines do not require ic tubation. There are two major types of positive pressure ventilator Pressure cycle ventilators were the first available.* Thes ventilators respond to a preset pressure, such as 20 cm c water. When this pressure is achieved in the lungs the ven tilator stops and allows the patient to exhale. This mean that in certain disease states which are accentuated by higl or changing intrapulmonary pressures, these ventilators ma; deliver inadequate or variable volumes of air. Intermitten positive pressure breathing is usually done with pressun cycle ventilators. Volume cycle ventilators1* deliver a preset volume. Thi: preset volume can be accomplished despite an increase ir resistance to air flow or expansion of lungs. These ventilator: deliver a relatively constant volume and percentage ofoxy gen per minute. They are easy to control and maintain, anc can be equipped with alarm systems. Copyright 1977, American Society of Hospital Pharmacists, Inc. All rights reserved- * Bennett. PR. 1 and PR. 2; and Bird, Mark 7 and Mark 8. b MA-1, Emerson, OH. 22559001 BFG21544 362 Toxicological Aspects of DEHP Studies have shown a wide variation regarding both ani,nal toxigenicity and teratogenicity of a number of phthalic .loid esters used in PVC plastics. An excellent review of phthalate ester toxicity has been done by Autian.34 The oral and parenteral toxicity of DBHP appears to be if a low order following both acute and long-term studies. However, under appropriate conditions, DEHP has been i lemonstrated to have significant effects on a number of bi ological systems/15 Perhaps the most interesting is the sen-itivity of embryonic heart cells to DEHP. At DEHP levels . 'btained in human blood stored in vinyl plastic bags, 97-98% of these cells were killed in culture medium. DEHP has been shown to either modify or abolish vas cular response to physiological stimuli.38 High doses of DEHP have caused early fetal deaths and semisterility in mice.37 DEHP has been demonstrated in the developing rat fetus from early embryogenesis to birth.3 One study was unable to correlate the tissue content of DEHP with the transfusion histories in the dog and rat as well as man.39 The investigators suggested that environ mental or possibly endogenous sources of DBHP are of greater consequence than the low-level parenteral admin istration of administered blood products stored in PVC blood bags. They concluded that PVC stored blood is not a significant source of tissue DEHP in humans probably be cause of its rapid metabolism and excretion in vivo. A recent study evaluated the effects of DEHP on hepatic function and histology in the rhesus monkey undergoing chronic transfusion.40 DEHP was solubilized resulting from leaching by platelets or plasma stored in PVC blood bags. The average cumulative amount of DEHP infused in one year was 21.3 mg/kg. Four of the seven PVC transfused monkeys had abnormal "Tc liver-spleen scan ratios, four of the seven demonstrated abnormal BSP clearance and six of the seven had abnormal liver histopathology upon com pletion of transfusion therapy. Cost As with other pharmaceuticals, the quantity purchased of large-volume parenterals is the determining factor as to cost. In general, plastic containers have now been priced competitively with glass. Conclusion From an administrative and financial standpoint, it would appear that if plastic,containers were not priced competi tively with glass, there would be no compellingjustification to purchase them. There are advantages and disadvantages to both plastic and glass containers. The lack of particulate matter in plastic containers, as suggested by some investi gators, may be medically outweighed or equal to the presence of plasticizers in the solutions found in plastic containers. Thus from a medical point of view, various justifications can he presented for both glass and plastic containers. PLASTIC INTRAVENOUS FLUID CONTAINERS References 1. Anon: The United States pharmacopeia, 19th rev. The United States Pharmacopeial Convention, Inc., Rockville, Maryland, 1975, p 7,648. 2. Hansen JS and Hepler CD: Contamination of intravenous solutions by airborne microbes, Am J Hosp Pharm 30:326-331 (Apr) 1973. 3. Poretz DM, Guyn JB, Jr, Duma RJ et at: Microbial containnation of glass bottle (open-vented) and plastic bag (clased-nonvenled) intravenous fluid delivery systems, Am J Hasp Pharm 31:726-732 (Aug) 1974. 4. Kundson RD, Walter CW and Scott JA: In-use testing of sterility of intravenous solutions in plastic containers. Surgery 73:778-781 (May) 1973. 5. Letcher Kl, Thrupp LD, Schapiro DJ et al: In-use contami nation of intravenous solutions in flexible plastic containers. Am J Hasp Pharm 29:673-677 (Aug) 1972. 6. Duma RJ, Warner JF and Dalton HP: Septicemia from in travenous infusions, N Engl J Med 284:257-260 (Jan 4) 1971. 7. Turco SJ and Davis NM: Particulate matter in intravenous infusions fluids--phase 3, Am J Hosp Pharm 30:611-613 (Jul) 1973. 8. Whitlow RJ, Needham TE and Luzzi LA' Generation of particulate matter in large-volume parenteral containers, J Pharm Sci 63:1610-1613 (Oct) 1974. 9. Needham TE and Luzzi LA Particulate matter in polyvinyl chloride intravenous bags, N Engl J Med 209:1256 (Dec 6) 1973. 10. Darby TD and Ausman RK: Particulate matter in polyvinyl chloride intravenous bags, N Engl J Med 290:579 (Mar) 1974. 11. MacDonald A Permeation of water vapour through plastic containers for intravenous infusion fluids, J Hosp Pharm 32: 174-175 (Sep) 1974. 12. Turco S and King RE: Sterile dosage forms. Lea and Pebiger, Philadelphia, Pennsylvania. 1974, p 140. 13. Stolar MH: National survey of selected hospital pharmacy practices. Am J Hosp Pharm 33:225-230 (Mar) 1976. 14. Williams RHP: Potassium overdosage: a potential hazard of non-rigid parenteral fluid containers, Br Med J1:714-715 (Mar 24) 1973. 15. Lankton JW, Siler JN and Neigh JL: Hyperkalemia after administration of potassium from nonrigid parenteral-fluid con tainers, Anesthesiology 39660-661 (Dec) 1973. 16. Bighley LD.WilleJ and Lach JL: Mixing of additives in glass and plastic intravenous fluid containers. Am J Hosp Pharm 31: 736-739 (Aug) 1974. 17. Anon: Viaflex containers, Med Letter Drug Ther 14:No. 19 (Sep 15) 1972. 18. Gesler RM and Kartinos NJ: Contamination ofblood stored in plastic packs. Lancet 2:151 (Jul 18) 1970. 19. Guess WL and Autian J: A study of polyvinyl chloride blood bag assemblies, u alteration or contamination of ACD solutions. Drug Intell 1:120-127 (Apr) 1967. 20. Marcel YL and Noel SP: Contamination of blood stored in plastic packs. Lancet 165-36 (Jan 3) 1970. 21. Jaeger RJ and Rubin RJ: Contamination of blood stored in plastic packs. Lancet 2:151 (Jul 18) 1970. 22. Jaeger RJ and Rubin RJ: Migration of a phthalate ester plasticizer from polyvinyl chloride blood bags into stored human blood and its localization in human tissues, N Engl J Med 28: 1114-1118 (Nov 30) 1972. 23. Jaeger RJ and Rubin RJ: Plasticizers from P.V.C., Lancet 2:778 (Oct 10) 1970. 24. Jaeger RJ and Rubin RJ: Plasticizers from plastic devices: extraction, metabolism, and accumulation by biological systems. Science 170:460-461 (Oct) 1970. 25. Eubanks R and Autian J: Evaluation ofa polyethylene blood bag, Am J Hosp Pharm 28:172-177 (Mar) 1971. 26. Neefgaard J, Nielson B, Faurby V et al: Plasticizers in P.V.C. and the occurrence of hepatitis in a hemodialysis unit, Scan if Urol Nephrol 5:141-145,1971. 27. Rubin RJ: Storage ofaqueous solutions for parenteral infu sion, Lancet 1665 (Apr 29) 1972. 28. Kartinos NJ: Personal communication, Aug 8,1973. 29. Chiou WL and Moorhatch P: Interaction between vitamin American Jounal of Hospital Pharmacy Vol 34 Apr 1977 BFG21545 161 ZQQ6SSZZ > WARNING: Do not use plastic container in series connec tions. Such use could result in air embolism due to residual air (approximately IS ml) being drawn from the primary con tainer before administration of the fluid from the secondary contajber is completed. Certain solutions should not be ad ministered simultaneously with blood through the same infusion set because of the possibility of pseudoagglutina tion. Leaching and Adsorption Considerations A major concern regarding the use of plastic i.v. solution containers is the possible diffusion of toxic stabilizers and plasticizers from the plastic into the i.v. solution as well as sorption of additives from the solution by the plastic. The soft plastic containers are composed of PVC and various plasticizers, stabilizers and catalysts. One plasticizer used is di-2-ethylhexyl phthalate ester (DEHP), also known as dioctyi phthalate.18 Studies demonstrating the leaching of plasticizers from bags used to store blood and from hemodialysis equipment were published several years prior to the introduction of plastic bags for large-volume parenteral solutions. In 1967 Guess et al19 studied the alteration or contamination of anticoagulant citrate dextrose (ACD) solutions stored in PVC blood bag assemblies. Infrared analysis revealed DEHP as the main contaminant. In a subsequent report Marcel and Noel20 reported what they thought to be dihexyl phthalate as a contaminant of blood stored in plastic packs using infrared spectropho tometry and gas-liquid chromatography. They found con centrations up to 11.5 mg/100 ml after storage for 21 days. In a follow-up report, Gesler and Kartinos18 identified di octyl phthalate in the extracts of plasma stored in plastic packs using thin layer chromatography. Jaeger and Rubin21-22 found DEHP in concentrations of 5 to 7 mg/100 ml of blood stored for 21 days. The rate of migration was found to be 2.5 ppm/day. Furthermore, tissues from two patients who had been transfused were found to contain quantities of DEHP ranging from 69 to 200 ng/g dry-weight. In another reportJaegerand Rubin rejected the contention of Gesler and Kartinos that the margin of safety of DEHP is equivalent to water.23 In this study they further reported the extraction of two phthalate plasticizers by blood used in hemodialysis and heart-lung bypass systems. It was these communications during 1970 that stimulated the controversy on the extraction of DEHP. The studies of Jaeger and Rubin were published in their entirety later that. year.24 In 1971 Eubanks and Autian29 reported on their evalua tion of polyethylene blood bags. The blood bags were tested for leaching when partially filled with ACD solution for up to 12 months at 5 C and room temperature. They found that a chemical contaminant (residue) was found in all storage conditions, but it was found to be nontoxic in biological systems using tissue culture, intradermal and mouse toxicity tests. A Danish report by Neergaard et al26 suggested that di ethyl phthalate migrated from hemodialysis tubing and found concentrations of 10-20 mg/liter in the perfusate. Up until this point we have reviewed the work done on the extraction of DEHP from PVC contaminating blood bags and hemodialysis equipment. The first report on investi gation of the possible migration of DEHP into i.v. solutions from plastic containers was made by Rubin in 1972.27 No levels greater than the control in excess of 0.24 ppm would be detected in normal saline, dextrose 5% water and 5% protein hydrolysate after storage for more than a year after manufacture. Further work by one ofus (S.P.L.) using nor mal saline-revealed the presence of foreign components when examined by ultraviolet spectrophotometry as evidenced by the appearance of distinct absorption bands at 280 nm and 225 nm. Kartinos agreed that these data represented trace amounts of leached plasticizers, the main component being DEHP.28 The next series ofevents on DEHP came when Chiou and Moorhatch29 reported on the sorption of vitamin A by plastic containers. They found 78% of 200 ml aqueous solution containing vitamin A (in the form of retinol acetate) was, retained by the plastic containers after 24 hours ofstorage'* at room temperature. The amount sorbed is a function of time, with 10% sorbed after two hours of storage. They at tributed the problem to the polysorbate 80 used as a solu bilizer. The work of Chiou and Moorhatch prompted Nedich to conduct a similar series ofexperiments. He found a rub ber-stoppered glass bottle plus set delivered 77% of the available 10,000 units of vitamin A/liter over a 10-hour pe riod while the plastic system delivered 71% over the same period of time. The solutions had been protected from light as Chiou and Moorhatch had done. In another set ofexper- iements in which the solutions were nonprotected from light, data showed a 61% delivery from the glass system and 49% from the plastic system.29 Additional work by Chiou and Moorhatch corroborated the subject of extractables from plastic containers.31 The ultraviolet absorption spectra of distilled water, normal saline and 5% dextrose solutions showed only a slight in crease after an unstated storage period at room temperature as compared with the negative findings ofRubin. Results on surfactant solutions (usually fat soluble vitamins) showed that chemicals were leached out after storage for up to 48 hours. Although the identity and concentrations of the leached chemicals were not firmly established, they esti mated that 2.5 mg of DEHP leached out to the 200 ml of 0.04% polysorbate 80 solution in 48 hours. It was their opinion that the manufacturer should disclose to the public , the names and amounts of the plasticizers, stabilizers and other chemicals added to the PVC and their acute and chronic toxicity data if available. It has been reported that insulin is adsorbed to glass infusion bottles, plastic i.v. tubing and plastic Lv. contain ers.32 A follow-up-study by Petty et al33 reported that 55% of insulin is adsorbed from solution by both glass and PVC containers within 15 seconds. In the presence of5% dextrose there appeared to be less adsorption by both the glass and PVC systems. 225S9003 PLASTIC INTRAVENOUS FLUID CONTAINERS . . .uld be less than the labeled maximum of 5 ppm. In light , > t lie above, further research is needed to elucidate the role , .i imitation in the shedding of particles encountered during i lie course of shipping. J water Vapor Transmission and Osmolarity The current USP permeation specifications state: "A hermetic container is impervious to air or any other gas ;;nder the ordinary or customary conditions of handling, shipment, storage, and distribution."1 A container is defined .is tight "if the moisture permeability exceeds 100 mg/day/ iiler in not more than one of the 10 test containers and ex ceeds 200 mg/day/Iiter in none of them."1 A comparative study of PVC and polypropylene bags was hone in England by MacDonald.11 Results showed that the polypropylene bag, which has been used in the Scandinavian countries for about 10 years, served as a far better protective harrier than the PVC bag manufactured by Smith and Nephew. Without the outer protective wrapper, Viaflex lost 1.6-4% of its nominal volume when stored at 25 C and 3375% relative humidity after 12 months as contrasted to 2-6% for Steriflex and 1-3.5% for the Smith and Nephew systems. Less than 1% water vapor transmission was noted with the SKilyprapyiene bags under the same storage conditions. The ulutions employed in the study were not identified. One must remember, however, that a bag is usually not stored without its overwrap for a long time. The permeability of the plastic to moisture transfer has been pointed out by others.12 In view of these findings, it appears that plastic containers do not satisfy the USP definition of a hermetic container. T'he results more closely approximate the definition of a tight container. Although this loss would not appear to be clinically significant insofar as concentration changes leading to a hypertonic solution, these studies do point out that the unit is not a truly closed system and a potential exists for gaseous entry into the system. A more recent study reported on comparative mixing of additives in i.v. solutions in glass bottles and PVC bags.1 The additives studied were chlorothiazide sodium, potas sium chloride and phenytoin sodium. Results showed there was adequate mixing when the additives were injected into an upright glass container or a plastic bag which was sub sequently hung in the infusion position and into a glass container in the infusion position. Poor mixing resulted when the injections were made into a plastic bag hanging in the infusion position. Based on the reported data. Table 1 illustrates the dra matic pooling phenomenon. The following statement appears in the manufacturer's directions for adding medication: NOTE: When adding Potassium Chloride or substances of similar density to the Viaflex* container, the initial contents of both ports should be evacuated by squeezing them while the bag is in the upright position, followed by the usual mix ing procedure. The manufacturer has attempted to reduce the hazard of pooling by shortening the length of the entry port. Ap parently this does not reduce the hazard of pooling of the additive but serves to reduce the accumulation of additive at the port of entry, hence mixing is still required. Breakage and PuncturabiUty Plastic containers are susceptible to accidental puncture which can create a point ofentry for bacteria or other con taminants.17 Care must be exercised when adding a drug through the additive port because of the possibility of puncturing the plastic with a needle.12 It is questionable whether the overwrap protects against such punctures. Such punctures may not be evident unless the bag and its contents are squeezed as recommended prior to leaving the pharma cy. Drug Additives A recent survey has shown that about 30% of hospital pharmacies have instituted an i.v. admixture service.13 A number of parameters should be considered in the use of nonrigid plastic parenteral fluid containers as far as drug additives are concerned. Generally poor mixing of drug additives is perhaps an inherent property of flexible plastic containers because of the positioning and length of injection site. The experiments of Williams14 indicated that when potassium chloride was added to 500 ml ofnormal saline in a plastic container, the added solution was pooled at the injection site leading to a hyperkalemic bolus. Two cases ofpotassium overdosage were reported by the author. A third case of potassium overdosage was reported by Lankton et al.ls They attributed the over dosage to poor mixing because of the design of the injection port. The degree ofmixing was dependent upon the distance the needle was introduced into the injection port when hanging in the infusion position. Series Connections Plastic containers should not be used in series connections. A warning statement by the manufacturer4 appears in the directions for use. It states: b See footnote a. * See footnote a. Table 1. Recoveries of Additives from First 100-ml aliquots from Glass and Plastic Parenteral Containers* Additives The oret Inverted ical Glass Bag Upright Glass Bag Potassium chloride (mEqlb ' 2 Phenytoin sodium 10 Chlorothiazide (mg)c 10 1.40 8.72 34.21 15.05 44.88 36688 1.80 9.15 -- 2.55 9.19 -- * Recalculated data of Sighley et al,4by the authors. b In dextrose 5% in water. c In Sodium Chloride Injection, USP. American Journal of Hospital Pharrjwrcy Vot 34 Apt 1977 BFG21547 359 :4s JS space requirement and the handling ease. The plastic con tainer, being less rigid than glass, requires support by virtue of shelf trays or boxes to allow for ease of identification and inventory control. In reference to handling, the plastic container is easier to hold and will not break on falling, but it does present diffi culty if an additive must be placed into the solution because of its lack of rigidity on standing. Although the currently available plastic containers offer advantages in reference to decreased weight and storage space as opposed to glass, the lack of rigidity presents problems in handling when manipulation is required. Environmental Contamination The single most important advantage claimed for plastic containers is that they require no air venting and, therefore, airborne contamination of sterile solutions is reduced. Hansen and Hepler2 reported on the contamination of intravenous solutions using the closed Cutter system, the open MacBick systems, the open system with air vent tube represented by the Baxter system and the Viaflex.system. They compared the extent of contamination from airborne microbes during the opening of the containers in unsterile air. The number of bacteria per cubic foot of air was deter mined with an air sampler and the number of bacteria which had entered the solution systems was determined by filtra tion. The investigators concluded that the Cutter closed system and Viaflex system offered significantly better pro tection against contamination by airborne microbes than did the open and open with tube systems. Human Touch Contamination Plastic containers* of large-volume parenteral'solutions have a separate entry port which allows for the administra tion set to be inserted within a closed sealed compartment When the administration aet spike is inserted, the outer part of the entry port is occluded before the internal membrane is penetrated. Because of this feature, someone cannot in advertently touch and contaminate the internal point of puncture. It is suggested that the rubber diaphragm of glass containers should be swabbed with an antiseptic solution before entry of the administration set spike. Even so, it is conceivable that someone may touch, and thereby contam inate, the rubber diaphragm. Poretz et al3 reported on the microbial contamination of glass bottle and plastic bag parenteral delivery systems. The frequency and potential for contamination of both systems were determined from data derived in studies simulating work and centralized admixture conditions. The plastic bags were associated with a higher frequency of contadfination than the glass bottles. The incidence of contamination of the plastic bags was 6.9%, compared with 1.3% for glass con tainers. While the source ofthe contaminant was uncertain. Travenol Laboratories, Inc., Deerfield, IL 60015. they concluded that human touch was an important factor. Other studies by Kundson et al found a lower contaminant incidence (0.88%) with plastic bags than with glass con tainers.4 Letcher et al5 determined the rate of contamination of solutions in plastic containers and administration sets under actual use conditions when the solutions and admixtures were prepared for administration and administered by nurses. Of 366 solutions sampled over a three-month period, 4.9% were found to be contaminated. The investigators concluded that this was a relatively low contamination rate with the plastic i.v. solution containers when compared to previously reported studies of other systems. Duma et al6 reported that clinically significant contami nation occurred while changing volume-control devices during the introduction of additives into the container or tubing, stemming, from the hands of personnel or from heavily contaminated environmental surfaces. While this study shows the problems ofcontamination using adminis tration devices for a glass system, no studies have been re ported with the plastic containers under similar condi tions. Particulate Matter Turco and Davis7 compared the particulate matter con tamination of i.v. solutions manufactured by four firms during 1972. They found that solutions in plsstic containers were least contaminated. The average number of particles greater than 5 from plastic containers was 76/liter, whereas the glass containers had averages of 204-488 par ticles. Specifically, plastic containers had averages of 70-96 particles greater than 6-jim in size, whereas normal saline in glass containers had averages of 217-803 particles/liter. Dextrose 5% in water in plastic containers had an average of 80 particles/liter greater than S /nn, whereas for glass containers the range was 98-577. Although the investigators did not offer an explanation why the plastic containers had significantly less particulate matter than the glass contain ers, they concluded that plastic containers may have offered less potential for particulate matter contamination at that time. A subsequent study by Whitlow et at8 generated partic ulate matter as colloidal-sized globules from polyvinyl chloride (PVC) i.v. bags containing normal saline using gyrorotatory agitation simulating conditions of a truck going over a bumpy road. After studying more than 600 bags they found that over 75% contained in excess of 20,000 parti cles/mi with a diameter of 2.3 to 5.0 /an. Characterization studies done previously by Needham and Luzzi identified the particulates as di-2-ethylhexyl phthalate (DEHP).9 Subsequent correspondence by Darby and Ausman10 re garding the conditions of agitation used by Needham and Luzzi indicated low particulate counts before shaking while drastic shaking produced microspheres of liquid plasticizer described as "pseudoparticles." On the basis of 20,000 par ticles/ml and an assumed diameter of 2 /im, the investigators attributed particulate levels in the order of0.1 ppm which asa 22559005 BFG21548 Ilians, in White PL and Nagy ME (eds): Total parenteral nutri tion, Publishing Sciences Group, Acton, Massachusetts, 1974, p 3. Dud rick ST, Steiger E, Long JM et at: General principles and n-chniques of intravenous hypernlunentation. In Cowan GS and Slieolz WL (eds): Intravenous hyperalimentation, Lea& Febiger, I'liiladelphia, Pennsylvania, 1972, p8-9. 1. Shils ME: Guidelines for total parenteral nutrition, J Am Med Usoc 220:1721-1729 (Jun 26) 1972. 5. Fcrrebee JW, Johnson BB, Mithoefer JG et at: Insulin and .ulrenocorticotropin labeled with radio-iodine. Endocrinology 33:277-283 (Mar) 1951. 6. Kreinkel N and Goodner C l: Carbohydrate metabolism in pregnancy, i: the metabolism of insulin by human placental tissue, J Clin tnuest 29:116-131 (Jan) I960. 7. Hill JB: The adsorption of 131-1 insulin to glass. Endocri nology 65:515-517 (Sep) 1959. 8. Petty C and Cunningham NL: Insulin adsorption by glass infusion bottles; polyvinylchloride infusion containers and intra venous tubing. Anesthesiology -#0:400-404 (Apr) 1974. 9. Weisenfeld S, Podolsky S. Goldsmith L et ah Adsorption of insulin to infusion bottles and tubing, Diabetes 17:766-771 (Dec) 1968. 10. Wiseman R, Jr and Baltz BE: Prevention of insulin-I-131 adsorption to glass. Endocrinology 68:354-356 (Feb) 1961. 11. Felig P: Insulin: rates and routes of delivery (editorial), JV Engl J Med 291:1031-1032 (Nov 7) 1974. 12. Genuth SM: Constant intravenous insulin infusion in diabetic ketoacidosis, J Am Med Assoc 223:1348-1351 (Mar 19) 1973. 13. Kidson W, Casey J, Kraegen E et al: Treatment of severe diabetes mellitus by insulin infusion, Br Med J 2:691-694 (Jun 29) 1974. . 14. Page MM, Alberti KGMM, Greenwood R et al: Treatment of diabetic coma with continuous low-dose infusion of insulin. Hr Med J 2:687-690 (Jun 29) 1974. 15. Semple PF, White C and Manderson WG: Continuous in travenous infusion ofsmall doses ofinsulin in treatment ofdiabetic ketoacidosis. Hr Med J 2:694-698 (Jun 29) 1974. 16. Gieseclce AH. Spier CS and Jenkins MT: Management of diabetes mellitus during anesthesia and surgery, Tex Soc J Med 60:840-843 (Oct) 1964. 17. Greenwood FC et al: The preparation of 13l-I-labe!ed human growth hormone of high specific radioactivity, Biochem J 89: 114-123,1963. 18. Remington RD and Schork MA: Statistics with applications to the biological and health sciences, Prentice-Hall, Inc., Englewood Cliffs, New Jersey, 1970, pp 282-288. 19. Hull RL: Physiochemical chemical considerations in intra venous hyperalimentation. Am J Hosp Pharm 37:236-243 (Mar) 1974. 20. Package insert, Abbott Laboratories, North Chicago, Illinois, Aminosol 5% in dextrose 5% in water. 21. Package insert, McCaw Laboratories, Santa Ana, California, FreAmine II, (Oct) 1973. Am J Hosp Pham 34:357-362 (Apr) 1977 Review of current knowledge of plastic intravenous fluid containers Robert J. Petrlck, Spiro P. Loucas, Jerome K. Cohl and Bernard Mehl A review of the features of plastic intravenous fluid containers is presented. The following topics are discussed: (1) handling and storage; (2) environmental and human contamination; (3) particulate matter, (4) water vapor transmission; (5) drug additives; (6) leaching and adsorption; (7) possible toxicity, and (8) cost. It is concluded that variousjustifications can be presented for both glass and plastic contain- Key Words: Additives; Adsorption; Containers; Contamination; Costs; Glass; Injections; Leaching; Particles; Plastics; Storage; Toxicity Major characteristics of the ideal plastic container for the storage and administration of large-volume parenterals should include the following: 1. Allow visual inspection ofits contents prior to administra tion, Z Be chemically inert to minimize changes in the properties of the solution, 3. Not contribute to particulate contamination, 4. Not interact with additives, 5. Act as a barrier to diffusions! fluid loss, and 6. Maintain sterility of its contents in the presence or absence of drug additives prior to and during administration. The packaging and storage recommendations for large volume parenterals found in the current United States Pharmacopeia are stated as follows: "Preserve in single-dose containers, preferably of Type I or Type II glass."1 Largevolume parenteral solutions have been available in plastic containers since 1971. Because plastic containers for these solutions deviate from what is preferred by the USP we felt it would be valuable to discuss the advantages and disad vantages of plastic containers for large-volume parenteral solutions. The purpose of this paper is toaid hospital phar macists in evaluating a plastic parenteral delivery system. Robert J. Patrick, Phrra-D, Mi), ii Associate Director ofScientific In formation. Pfizer Laboratories Division, Pfizer, Inc., New York, NY 10017. Spiro P. Loucas, ph.D, is Director of Quality Control; Jerome K. Cohl, is Assistant Director of Clinical Services; and Bernard Mehl, M.BA, is Director, Department of Pharmacy, and Assistant Director, ML ' Sinai Hospital and Medical Center, New York. Copyright 1977. American Society of Hospital Pharmacists. Inc. All rights reserved. Handling and Storage The physical handling and storage of large-volume par enterals present problems both in the required space and the movement of these products. Although the weight ofa glass container is more than that of a plastic container, perhaps of equal significance is the 3S7 BFG21549 22559006