Safe disconnection of 5-fluorouracil elastomeric pumps: The benefit of a closed-system-transfer device designed for cytotoxic drug administration/perfusion

Background: Occupational exposure to cytotoxic drugs can lead to significant health problems. This study was designed to evaluate the risk of 5-fluorouracil (5-FU) contamination for nurses when disconnecting the infusion line of an elastomeric pump from a non-coring needle, by comparing three configurations: the first one using standard Male and Female Luer lock (Group 1), the second one using a needle-free connector (NFC) and a Male Luer lock (Group 2) and the third one using a closed-system transfer device (CSTD), Qimono® (Group 3). Methods: In this in vitro study, 10 elastomeric pumps for each of the three groups were filled with 5-FU and a tissue mimicking the patient’s arm was placed below the connection between the infusion line and the tubing of non-coring needle. After 48 h of infusion, disconnection was performed by a nurse with a wipe soaked in a mix of chlorhexidine and isopropyl alcohol in order to mimic care practices. For each pump, the tissue, the pair of gloves and the wipes used during the disconnection were collected for analysis. Results: Median level of overall 5-FU contamination (gloves + wipes + tissues) in group 3 was significantly lower than in group 1 ( p = 0.018) and group 2 ( p = 0.036). There was no difference between groups 1 and 2. Results per sample type showed no difference in contamination between the three configurations for the gloves as well as for the tissues. Concerning the wipes, the lowest contamination was observed in group 3, representing a mean reduction of 61% compared to group 1 and a mean reduction of 43% compared to group 2. Conclusion: The use of Qimono® appears to significantly reduce 5-FU contamination when disconnecting infusion lines of an elastomeric pump unlike NFC and standard Luer lock.

Optimising an Infusion Protocol Containing Cefepime to Limit Particulate Load to Newborns in a Neonatal Intensive Care Unit

Background: In neonatal intensive care units (NICUs), the simultaneous administration of drugs requires complex infusion methods. Such practices can increase the risk of drug incompatibilities resulting in the formation of a particulate load with possible clinical consequences. Methods: This paper evaluates strategies to reduce the particulate load of a protocol commonly used in NICUs with a potential medical incompatibility (vancomycin/cefepime combination). The protocol was reproduced in the laboratory and the infusion line directly connected to a dynamic particle counter to evaluate the particulate matter administered during infusion. A spectrophotometry UV assay of cefepime evaluated the impact of filters on the concentration of cefepime administered. Results: A significant difference was observed between the two infusion line configurations used in the NICU, with higher particulate load for cefepime infused via the emergency route. There was no change in particulate load in the absence of vancomycin. A filter on the emergency route significantly reduced this load without decreasing the cefepime concentration infused. Preparation of cefepime seemed to be a critical issue in the protocol as the solution initially contained a high level of particles. Conclusion: This study demonstrated the impact of a reconstitution method, drug dilution and choice of infusion line configuration on particulate load.

Assessment of efficacy of postinfusion tubing flushing in reducing risk of cytotoxic contamination

Purpose Infusion of cytotoxic drugs carries the risk of occupational exposure of healthcare workers. Since disconnecting an infusion line is a source of contamination, flushing of tubing after infusion of cytotoxic agents is recommended, but the optimal volume of rinsing solution is unknown. The objective of this study was to assess whether postinfusion line flushing completely eliminates cytotoxics. Methods Infusions were simulated with 3 cytotoxics (gemcitabine, cytarabine, and paclitaxel) diluted in 5% dextrose injection or 0.9% sodium chloride injection in 250-mL infusion bags. Infusion lines were flushed using 5% dextrose injection or 0.9% sodium chloride solution at 2 different flow rates. The remaining concentration of cytotoxics in the infusion line was measured by a validated high-performance liquid chromatography (HPLC) method after passage of every 10 mL of flushing volume until a total of 100 mL had been flushed through. Results All cytotoxics remained detectable even after line flushing with 80 mL of flushing solution (a volume 3-fold greater than the dead space volume within the infusion set). Gemcitabine and cytarabine were still quantifiable via HPLC even after flushing with 100 mL of solution. Efficacy of flushing was influenced by the lipophilicity of drugs but not by either the flushing solvent used or the flushing flow rate. After 2-fold dead space volume flushing, the estimated amount of drug remaining in the infusion set was within 0.19% to 0.56% of the prescribed dose for all 3 cytotoxics evaluated. Conclusion Complete elimination of cytotoxics from an infusion line is an unrealistic objective. Two-fold dead space volume flushing could be considered optimal in terms of administered dose but not from an environmental contamination point of view. Even when flushed, the infusion set should still be considered a source of cytotoxic contamination.

Understanding IV antimicrobial drug losses: the importance of flushing infusion administration sets

Background IV drugs are commonly prescribed for inpatient treatment. Where administered as infusions, drug dose loss is incurred if the infusion line is not flushed. Underdosing of IV antimicrobials is of particular concern as reduced treatment efficacy increases the risk of patient deterioration (including sepsis) and development of antimicrobial resistance. Objectives To quantify drug loss, raise awareness and provide recommendations to address this patient safety risk effectively. Methods Percentage drug loss of 39 IV antimicrobials was calculated for a theoretical patient case scenario, using residual volumes for IV infusion lines utilized within this acute healthcare setting. An adult male patient (70 kg) with good renal function was assumed for drug dosing. Infusion volumes and doses are based on a widely used IV administration guide. Results Data revealed the scope and extent of antimicrobial drug losses where infusion lines were not flushed as ranging from 2% to 33%. More than 10% of the drug would be lost for 26 of the 39 antimicrobials assessed, with five of these yielding over 20% loss. Conclusions The authors suggest that unintentional antimicrobial underdosing is going unnoticed in clinical practice. Where IV infusion is necessary, flushing of the infusion line to ensure total dose administration is strongly recommended. Risks associated with flushing lines (fluid overloading, bolus dosing, etc.) can be managed with simple measures. The authors call for a national body-led approach to effectively influence healthcare organizations in review of IV administration protocols, ensuring patient safety and care in the NHS.

Concomitant placement of dialysis and infusion catheters in the right internal jugular vein in the intensive care setting: Is it safe?

Purpose: This study examined the safety and efficacy of placing both a central venous dialysis catheter and a central venous catheter for infusion in the right internal jugular vein compared to only a central venous dialysis catheter. Methods: We conducted a retrospective chart review for all adult patients who underwent the placement of the right internal jugular dialysis catheter by a single surgeon. Patients were grouped based on whether they received a tunneled dual lumen dialysis catheter alone or in combination with a central venous infusion catheter in the right internal jugular vein. Catheter-related thrombosis, line infections, line malfunctions, pneumothorax, and need for line replacement were evaluated. Results: There were 97 patients in the dialysis catheter and central venous infusion line group and 63 patients in the dialysis catheter only group. The two groups were not different with regard to age (62.1 ± 16.3 years vs 57.9 ± 17.6 years) and gender (47.4% male vs 55.6% male). No significant differences were found in the incidence of thrombosis (1.0 % vs 0.0%, p > 0.999), line infection (2.1% vs 0.0%, p = 0.519), or line malfunctions (2.1% vs 0.0%, p = 0.516) in patients who did or did not have a central venous infusion catheter placed concomitantly with the dialysis catheter, respectively. No patients in either group had a pneumothorax. Conclusions: Although not currently utilized with frequency, these preliminary data indicate that placing both a dual lumen dialysis catheter and central venous infusion catheter in the right internal jugular simultaneously could be a viable option.

Fast Hypothermia Induced by Continuous Renal Replacement Therapy Alleviates Renal and Intestinal Injury After Cardiac Arrest in Swine

Background: Renaland intestinal damagelead tomultiple organ dysfunction and death after cardiopulmonary resuscitation (CPR), and can be partly mitigated by therapeutic hypothermia. Currently, continuous renal replacement therapy (CRRT) was demonstrated to be an effectiveway to induce hypothermia. In the present study, we aimed to investigate the influence of CRRT cooling on renal and intestinal damage after CPR based on a porcine model.Methods: 32swine were subjected to ventricular fibrillation for 8 min, while defibrillation was performed at 5 min of CPR. All pigs were randomly allocated to receive CRRT (n = 9), surface cooling (SC, n = 9), normothermia (NT, n = 9) or sham control (Control, n = 5)at 5 min post resuscitation. In the CRRT group, the pigs werecooled by the combination of8-hr CRRT and16-hr SC,a rate of 180 ml/min of blood flow was initially set with the infusion line submerged in 4 °C of ice water. In the SC group, pigs were cooled by the 24-hr SC.As to theNT and Controlgroups, thetemperatures were maintained at a normal range. The levels of creatinine (Cr), blood urea nitrogen (BUN), intestinal fatty acid binding protein (IFABP) and diamine oxidase (DAO) in serum were measured at baseline and at 1, 3, 6, 12, 24and30h post resuscitation. Additionally, tissues of kidney and intestine were harvested, from which the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), the contents of malondialdehyde (MDA), activities of superoxide dismutase (SOD) and theapoptosis levels were analyzed.Results:After resuscitation, the blood temperature decreasedsignificantlymore rapidlyin the CRRT group than in the SC group (9.8±1.6vs. 1.5±0.4 ℃/h, P <0.01). The levels of Cr, BUN, IFABP and DAOafter resuscitation were significantly lower in the two hypothermic groupscompared with the NT group. Furthermore, from pathological evidence, cooling induced by CRRTalleviated post-resuscitation renaland intestinal injury compared to SC.Conclusion:Fast hypothermia induced by continuous renal replacement therapy was superior to surface cooling in mitigating renal and intestinal injury post resuscitation.

Fast Hypothermia Induced by Continuous Renal Replacement Therapy Alleviates Renal and Intestinal Injury after Cardiac Arrest in Swine

Background: Renal and intestinal damage lead to multiple organ dysfunction and death after cardiopulmonary resuscitation (CPR), and can be partly mitigated by therapeutic hypothermia. Currently, continuous renal replacement therapy (CRRT) was demonstrated to be an effective way to induce hypothermia. In the present study, we aimed to investigate the influence of CRRT cooling on renal and intestinal damage after CPR based on a porcine model.Methods: 32 swine were subjected to ventricular fibrillation for 8 min, while defibrillation was performed at 5 min of CPR. All pigs were randomly allocated to receive CRRT (n = 9), surface cooling (SC, n = 9), normothermia (NT, n = 9) or sham control (Control, n = 5) at 5 min post resuscitation. In the CRRT group, the pigs were cooled by the combination of 8-hr CRRT and 16-hr SC, a rate of 180 ml/min of blood flow was initially set with the infusion line submerged in 4 °C of ice water. In the SC group, pigs were cooled by the 24-hr SC. As to the NT and Control groups, the temperatures were maintained at a normal range. The levels of creatinine (Cr), blood urea nitrogen (BUN), intestinal fatty acid binding protein (IFABP) and diamine oxidase (DAO) in serum were measured at baseline and at 1, 3, 6, 12, 24 and 30h post resuscitation. Additionally, tissues of kidney and intestine were harvested, from which the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), the contents of malondialdehyde (MDA), activities of superoxide dismutase (SOD) and the apoptosis levels were analyzed. Results: After resuscitation, the blood temperature decreased significantly more rapidly in the CRRT group than in the SC group (9.8 ± 1.6 vs. 1.5 ± 0.4 ℃/h, P < 0.01). The levels of Cr, BUN, IFABP and DAO after resuscitation were significantly lower in the two hypothermic groups compared with the NT group. Furthermore, from pathological evidence, cooling induced by CRRT alleviated post-resuscitation renal and intestinal injury compared to SC.Conclusion: Fast hypothermia induced by continuous renal replacement therapy was superior to surface cooling in mitigating renal and intestinal injury post resuscitation.

Safe Practice of Y-Site Drug Administration: The Case of Colistin and Parenteral Nutrition

A serious problem in everyday clinical practice is the co-administration of drugs using the same infusion line. Potential complications of co-administration of incompatible drugs include precipitation in the infusion line or central venous catheter leading to its occlusion. Administration of precipitate and large lipid droplets into the venous system may lead to the embolization of capillaries and local or systemic inflammatory reactions, with the consequences of venous thrombosis, chronic venous insufficiency, and even pulmonary embolism. The co-administration of drugs must always be confirmed and clearly defined. The study aimed to determine the interaction between colistin (COL) in the dose used during intermittent hemodialysis and five different ready-to-use PN admixtures (PN) (Kabiven, Smofkabiven, Olimel N9E, Nutriflex Lipid Special, and Nutriflex Omega Special). COL-PN compatibilities were tested by comparing physicochemical properties (pH, zeta potential, lipid emulsion particle size) of COL and PN at three time points: immediately after sample preparation, after ten minutes, and after four hours. No changes in the visual inspection were observed. Both PN without COL and COL-PN samples remained white, homogeneous oil-in-water emulsions with no signs of phase separation, precipitation, or color change. There were no significant changes in pH, and the mean droplet diameter remained below the acceptance limit of 500 nm. The zeta potential and osmolality of COL-PN samples ranged from −21.4 to −7.22 mV and from 567 to 1304 mOsm/kg, respectively. The COL does not influence the physical stability of studied PN admixtures. The co-infusion of COL with Kabiven, Nutriflex Lipid Special, Olimel N9E, Nutriflex Omega Special, and Smofkabiven is possible in the dose used during intermittent hemodialysis.

Design and practical evaluation of a shielded application system for intravenously administered radionuclide therapies

Aim Intravenous radionuclide therapies are gaining importance. With the increased frequency of these therapies, safe application procedures in combination with effective radiation protection are needed. We present a shielded system which can be universally used for the application of liquid radiopharmaceuticals. Materials and methods The application system consists of a cuboidal box made of lead with stainless steel coating, an inner layer of polymethyl methacrylate (PMMA), a disposable line/bottle system, and a medical infusion pump. No proprietary disposable parts are used. The system was tested and validated ex-vivo, and evaluated for Lu-177 peptide receptor radionuclide and for radioligand therapies (PRRT, RLT). Results Construction of the application system was performed in accordance with the physical characteristics of the used isotopes. 10 validation procedures with 1 GBq Tc-99m-pertechnetate confirmed functionality. 38 PRRT and 13 RLT procedures were performed successfully and completely. At least 98 % of the prescribed activities were infused. No leakage of radioactivity occurred. Dose rate measurements showed that the radiation in the box is shielded completely, and that exposure arises only from the infusion line outside the box and from the patient. Conclusion The presented application system for intravenous radionuclide therapies is feasible, safe, and cost-efficient. It has been shown that Lu-177-PRRT and -RLT can be performed without complications while ensuring nearly complete infusion of the prescribed radiopharmaceutical dose. Radiation exposure of the applying physician and other staff is low. The construction of the shielding box ensures complete shielding of all radionuclides currently used for radiomolecular therapies.