Nanosponges: As a Dynamic Drug Delivery Approach for Targeted Delivery

Recent advancements in nanotechnology have resulted in improved medicine delivery to the target site. Nanosponges are three-dimensional drug delivery systems that are nanoscale in size and created by cross-linking polymers. The introduction of Nanosponges has been a significant step toward overcoming issues such as drug toxicity, low bioavailability, and predictable medication release. Using a new way of nanotechnology, nanosponges, which are porous with small sponges (below one microm) flowing throughout the body, have demonstrated excellent results in delivering drugs. As a result, they reach the target place, attach to the skin's surface, and slowly release the medicine. Nanosponges can be used to encapsulate a wide range of medicines, including both hydrophilic and lipophilic pharmaceuticals. The medication delivery method using nanosponges is one of the most promising fields in pharmacy. It can be used as a biocatalyst carrier for vaccines, antibodies, enzymes, and proteins to be released. The existing study enlightens on the preparation method, evaluation, and prospective application in a medication delivery system and also focuses on patents filed in the field of nanosponges.Copyright © 2023 The Authors.

Parietex Mini Male Sling for Stress Urinary Incontinence at the Time of Three Piece Penile Prosthesis: Technique and Outcomes

INTRODUCTION AND OBJECTIVE: Male stress urinary incontinence (SUI) and climacturia are often comorbid with erectile dysfunction (ED) post prostatectomy. While the inflatable penile prosthesis (IPP) is the gold standard surgical option for ED, there are many surgical options for male SUI as well as climacturia including bulking agents, Virtue male sling, AdVance>= male sling, mini Jupette with IPP, and artificial urinary sphincter (AUS). We present our technique and outcomes for mini male sling (MMS) with IPP insertion for mild SUI and climacturia using a hydrophilic monofilament polyester mesh. METHOD(S): After obtaining IRB approval, a retrospective review of all IPPs performed by a single high volume surgeon was performed. Those men who underwent IPP insertion with concomitant MMS were analyzed. The technique of MMS placement involves measurement of an approximately 5x3cm Parietex>= mesh (Covidien, MN) and overlying this ventrally over the bulbar urethra. The Parietex>= mesh includes a hydrophilic absorbable collagen film to minimize tissue reaction and risk of erosion. The lateral edges of the mesh are sutured to the 3- and 9 o'clock positions on the left and right corporal bodies, respectively, using a nonabsorbable, braided suture in an interrupted fashion. Mesh is sutured just proximal to the corporotomy sites. Tightness of mesh was measured using the proximal end of a Debakey forceps, with ease of passage when IPP deflated and inability to pass forceps when IPP inflated indicative of proper sizing. RESULT(S): A total of 63 men underwent IPP with MMS between January 2018 and October 2022. All patients had ED after radical prostatectomy. Average patient age was 67 years old, and average IPP size was 21cm with 1cm rear tip extender (RTE). A total of 59 men had SUI, with average pad per day (PPD) of 1.5. Twenty-five men with SUI had comorbid climacturia, and 4 men had preoperative climacturia without SUI. Average PPD post IPP with MMS was 0.1. Of the 29 men with preoperative climacturia, only one did not have resolution of his symptoms post MMS. There was only one reported complication of acute urinary retention requiring temporary foley catheter placement. Two patients required subsequent AUS insertion for persistent SUI. There were no reported cases of infection or mesh erosion. CONCLUSION(S): The hydrophilic Parietex>= mesh is a safe, easy to use, nonreactive, and effective material for mini male sling insertion at the time of IPP placement for men with ED and mild/moderate SUI or climacturia.

Getting to the root of it: contact anaphylaxis from polyethylene glycol in a dental lubricant

A 46-year-old man with no known allergies or history of atopy was referred for the investigation of a severe anaphylactic reaction following root canal dental treatment. The procedure had been done under local anaesthetic and involved drilling the tooth, removal of dental pulp, cleaning and insertion of a temporary filling. Preliminary skin prick tests (SPTs) and intradermal tests were negative to natural rubber latex, articaine (the local anaesthetic used for his procedure), lidocaine and chlorhexidine. He had negative specific IgE to chlorhexidine and latex, and a negative lidocaine challenge, confirming that he was not allergic to lidocaine. He returned for further dental treatment, which was done without local anaesthetic. As the procedure was completed, he developed severe anaphylaxis again. He made a full recovery and his dentist was asked for detailed information and samples of all the materials used during the procedure. Subsequent SPT showed a positive weal of 12 x 6 mm to the dental lubricant, Glyde, which was used on both occasions. Its ingredients included polyethylene glycol (PEG) 4253. SPT to other high-weight macrogol-containing products showed positive reactions to a 5% lidocaine ointment, Movicol, EMLA cream and Depomedrone. On further questioning he recalled minor immediate irritation after using a brand of children's shampoo, but a SPT to the shampoo was negative. An open test, closed test and SPT to a lower-molecular-weight patch-test allergen (PEG400 in petrolatum) were negative. PEGs or 'Macrogols' are hydrophilic polymers used in food, cosmetics and pharmaceutical reagents. They have recently attracted attention as they are excipients in several COVID-19 vaccines and have been suggested as a possible cause of anaphylaxis. Anaphylaxis to higher-molecular-weight PEGs has been reported from the use of bowel preparations and parenteral steroids. There are a handful of reports of contact urticaria to PEG-containing medicaments. We report this case to raise awareness of severe immediate hypersensitivity to these apparently innocuous ingredients and a novel source of exposure. A low index of suspicion, lack of standardized nomenclature and commercial reagents for testing are current barriers to diagnosis.

An investigation into the aging of disposable face masks in landfill leachate

Due to the excessive use of disposable face masks during the COVID-19 pandemic, their accumulation has posed a great threat to the environment. In this study, we explored the fate of masks after being disposed in landfill. We simulated the possible process that masks would experience, including the exposure to sunlight before being covered and the contact with landfill leachate. After exposure to UV radiation, all three mask layers exhibited abrasions and fractures on the surface and became unstable with the increased UV radiation duration showed aging process. The alterations in chemical groups of masks as well as the lower mechanical strength of masks after UV weathering were detected to prove the happened aging process. Then it was found that the aging of masks in landfill leachate was further accelerated compared to these processes occurring in deionized water. Furthermore, the carbonyl index and isotacticity of the mask samples after aging for 30 days in leachate were higher than those of pristine materials, especially for those endured longer UV radiation. Similarly, the weight and tensile strength of the aged masks were also found lower than the original samples. Masks were likely to release more microparticles and high concentration of metal elements into leachate than deionized water after UV radiation and aging. After being exposed to UV radiation for 48 h, the concentration of released particles in leachate was 39.45 muL/L after 1 day and then grew to 309.45 muL/L after 30 days of aging. Seven elements (Al, Cr, Cu, Zn, Cd, Sb and Pb) were detected in leachate and the concentration of this metal elements increased with the longer aging time. The findings of this study can advance our understanding of the fate of disposable masks in the landfill and develop the strategy to address this challenge in waste management. Copyright © 2023 Elsevier B.V.

Weathering and degradation of polylactic acid masks in a simulated environment in the context of the COVID-19 pandemic and their effects on the growth of winter grazing ryegrass.

The COVID-19 pandemic has led to explosive growth in the production and consumption of disposable medical masks, which has caused new global environmental problems due to the improper disposal of these masks and lack of effective mask recycling methods. To reduce the environmental load caused by the inability of synthetic plastics to degrade, polylactic acid (PLA) masks, as a biodegradable environmentally friendly plastic, may become a solution. This study simulated the actual degradation process of new PLA masks in different environments by soaking them in various solutions for 4 weeks and explored the influence of the treated PLA fabric fibers on the growth of winter ryegrass. The results show that the weathering degradation of PLA fibers in water mainly occurs through the hydrolysis of ester bonds, and weathering leads to cheese-like and gully-like erosion on the surface of the PLA fiber fabric layer and finally to fiber fracture and the release of microplastics (MPs). The average number of MPs released within 4 weeks is 149.5 items/piece, the particle size is 20-500 µm (44%), and 63.57% of the MPs are transparent fibers. The outer, middle, and inner layers of weathered PLA masks tend to be hydrophilic and have lower mechanical strength. PLA fibers after different treatment methods affect the growth of winter ryegrass. PLA masks are undoubtedly a greener choice than ordinary commercial masks, but in order to confirm this, the entire degradation process, the final products, and the impact on the environment need to be further studied. In the future, masks may be developed to be made from more environmentally friendly biodegradable materials that can have good protecting effects and also solve the problem of end-of-life recycling. A SYNOPSIS: Simulation of the actual degradation process of PLA masks and exploration of the influence of mask degradation on the growth of winter ryegrass.

Office-Based Ureteral Stent Insertion Without Fluoroscopy under Minimal Sedation is Safe and Effective

Introduction &Objective: Acute renal colic due to obstructing stones has been a challenge for urologists to manage during the COVID-19 pandemic. Due to overwhelmed hospital resources, operating room (OR) time and staff became scarce, resulting in prolonged pain and suffering for patients. Early during the pandemic, we instituted an office-based ureteral stent placement protocol to relieve immediate discomfort. Later with less constrained OR availability, we extended this protocol to patients undergoing chronic stent changes. Method(s): Patients who presented with severe renal colic due to obstructing stones were offered immediate office-based ureteral stent placement under minimal sedation. Patients filled a prescription of diazepam 10mg and were brought to the procedure suite 2 hours later. Intramuscular ketorolac 15mg was given and 2% lidocaine lubricant jelly was inserted per urethra. Flexible cystoscopy was performed with a standard 16Fr scope, and the stent was placed through the cystoscope. For the first two cases, a 0.038" hybrid wire and 4.8fr stent were used while subsequently, a 0.035" stiff hydrophilic nitinol wire and 4.5fr stent were used. No intraoperative fluoroscopy was used. After stent placement, KUB X-Ray was done to confirm stent placement. Result(s): Seven patients (4 females, 3 males) with a mean age of 62.5 years and a mean BMI of 31.3 underwent an office-based procedure. Five stent insertions were done for obstructing ureteral stone (unilateral = 4, Bilateral = 1) and 2 stent changes for ureteral stricture and ureteral obstruction due to fibroids. In most cases, it was clear when the wire had gone past the stone, as there was immediate efflux of urine into the bladder. The efficiency of the procedure was greatly increased by changing the wire and stent size. Stent placement failed in one case due to overfilling of the bladder causing acute angulation of the ureteral orifice. The stent was later inserted under general anesthesia. Conclusion(s): Office-based ureteral stent insertion and exchange are safe and effective even in the absence of fluoroscopy. Further studies are needed to investigate predictors of success of office-based stent insertion, along with cost analysis to expand its use routinely.

PCL- And Gelatin-based Electrospun Biological Scaffolds For In Vitro Lung Tissue Engineering

Purpose/Objectives: Acute and chronic respiratory diseases constitute a substantial socioeconomic burden on a global scale, as made abundantly clear in the last two years with the rampant coronavirus disease 2019 (COVID-19) pandemic. Alas, the development of new therapies for pathological respiratory conditions has been hindered by the inadequacy of current preclinical models, which often fail to provide reliable predictions on drug safety and efficacy in humans. In particular, considerable anatomical and physiological differences between the respiratory systems of commonly used animal models and humans are one of the main issues leading to high drug attrition and clinical failure rates. Accordingly, the generation of physiologically relevant preclinical lung models for early drug development and pharmaceutical research is urgently needed. In this work, poly(ϵ-caprolactone) (PCL) and gelatin were used as raw materials to produce electrospun scaffolds for in vitro lung tissue engineering, in order to generate human biomimetic platforms for preclinical drug safety and efficacy testing. Methodology: PCL and gelatin were mixed at varying volume ratios: 1:0 (PP), 6:1 (PPG61), 4:1 (PPG41), and 2:1 (PPG21), so as to determine the optimal gelatin concentration for cell adhesion and growth. Poly(vinylpyrrolidone) (PVP) was added to every polymer mixture to facilitate the electrospinning process, and electrospun fibrous matrices were fabricated using a needleless electrospinning technique. Scaffold morphology, chemical composition, and wettability were characterized with scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and water contact angle analysis, respectively. Biocompatibility testing was performed using human bronchial (16HBE) and alveolar (A549) epithelial cell lines, consisting of cell metabolic activity, proliferation, and adhesion evaluation over two weeks of in vitro culture. Results: All polymer blends resulted in the formation of electrospun scaffolds with a nanofibrous structure. The addition of gelatin in PPG61 scaffolds improved fiber morphology compared to PP formulations, but increasing proportions of this polymer in PPG41 and PPG21 mats caused a larger number of defects, such as beading and branching. FTIR analysis confirmed the presence of PCL and PVP in PP scaffolds, as well as the addition of gelatin in all PPG blends. Moreover, as expected, all scaffolds were hydrophilic, with water contact angles below 90°, being suitable for protein adsorption and cell adhesion. Regarding 16HBE and A549 cell viability, surprisingly, no major differences were found between the different formulations over the two-week culture period, showing that all polymer blends were equally capable of promoting cell adhesion and growth. While PP scaffolds significantly outperformed PPG electrospun mats in early timepoints, no such differences were identified at the end of the experimental period. Conclusion/Significance: These results suggested that PCL, PVP, and/or gelatin blend electrospun scaffolds are conducive to lung epithelial cell adhesion and proliferation. Nevertheless, further studies investigating epithelial cell differentiation and function should be conducted to fully assess the suitability of these biomaterials as platforms for in vitro lung tissue engineering.

Microwave treatment to optimize physicochemical properties of modified Busil (Xanthosoma sagittifolium) starch

COVID-19 pandemic encourages the utilization of local food sources to ensure food availability. Busil (Xanthosoma sagittifolium) was readily available and affordable in Banjarnegara Regency in the Province of Central Java in Indonesia. However, the busil starch utilization was still rare due to the low functional properties of the native busil starch. The objective of this study was to explore busil starch physicochemical characterization enhancement after microwave irradiation treatment, especially on the stability of heat processing. This research was conducted in two steps. First, microwave treatment (with a variation of energy and irradiation time) of native busil starch (NBS), and the second was modified busil starch (MBS) physicochemical characterization. A rise in amylose was observed on MBS. SEM analysis was shown MBS granules are breakdown. Through viscosity, final viscosity, setback viscosity, peak time, and the pasting temperature of MBS generally were increased. Meanwhile, peak viscosity and breakdown viscosity of MBS was decreased. Thermal properties of MBS like onset (To), peak (Tp), and conclusion (Tc) temperatures were also increased. The degree of whiteness index (DW) of MBS was decreased. FTIR analysis has shown that microwave treatment did not cause functional group alteration. XRD analysis has also demonstrated no change in the diffraction pattern but a slight change in the crystallinity index. Generally, microwave treatment leads to MBS thermal stability and potentially broaden MBS utilization on food processing product.

Observation on the protective effects of 2 different protective stickers on facial injury/discomfort caused by protective appliances

Objective: To observe the protective effects of 2 kinds of protective stickers made from different materials on facial injury/discomfort caused by wearing protective appliances of military medical members in the medical team supporting Hubei, so as to provide reference for developing convenient and effective protective measures. Methods Totally 147 military medical members in the medical team supporting Hubei were surveyed by the self-designed questionnaire of facial injury/discomfort caused by wearing protective appliances. Cross-sectional survey of the facial injury/discomfort before and after using the protective gel stickers (Haishen stickers, developed by the Faculty of Pharmacy, Naval Medical University [Second Military Medical University]) or 3M hydrophilic dressing was conducted, and the protective effects of the 2 kinds of protective stickers on facial injury/discomfort were compared. Results A total of 78 medical members finished the questionnaires (62 cases with Haishen stickers and 16 cases with 3M hydrophilic dressings). The scores of facial injury/discomfort were significantly reduced in both groups after using the protective stickers (both, P<0.05);however, there was no significant difference between the 2 groups before or after using the protective stickers (both, P>0.05). The top 4 moderate-to-severe facial injury/discomfort were fogging of protective glasses/masks (85.9%, 67/78), skin indentation (80.8%, 63/78), pain at the contact sites (74.4%, 58/78) and sultry (71.8%, 56/78), and the overall proportion of moderate-to-severe injury/discomfort was 80.8% (63/78);after using the protective stickers, the top 4 moderate-to-severe facial injury/discomfort were fogging of glasses/masks (53.8%, 42/78), sultry (41.0%, 32/78), respiratory resistance (41.0%, 32/78) and skin indentation (38.5%, 30/78), with the overall proportion of moderate to severe injury/discomfort being 43.6% (34/78);and the top 4 improvement rates of facial injury/discomfort after using protective stickers were skin erosion (76.5%), skin redness (67.3%), pain at the contact sites (63.8%), and itching at the contact site (52.9%). Conclusion These 2 kinds of protective stickers made from different materials can improve the facial injury/discomfort caused by protective appliances, which is worth popularizing.

Microdroplet Impact Dynamics at Very High Velocity on Face Masks for COVID-19 Protection

Facial masks have become indispensable in daily life to prevent infection and spread through respiratory droplets in the era of the corona pandemic. To understand how effective two different types of masks (i.e., KF-94 mask and dental mask) are in blocking respiratory droplets, i) we preferentially analyze wettability characteristics (e.g., contact angle and contact angle hysteresis) of filters consisting of each mask, and ii) subsequently observe the dynamic behaviors of microdroplets impacting at high velocities on the filter surfaces. Different wetting properties (i.e., hydrophobicity and hydrophilicity) are found to exhibit depending on the constituent materials and pore sizes of each filter. In addition, the pneumatic conditions for stably and uniformly dispensing microdroplets with a certain volume and impacting behaviors associated with the impacting velocity and filter type change are systematically explored. Three distinctive dynamics constituting the masks and droplet impact velocity. The present experimental results not only provide very useful

Adopting Intrinsic Hydrophilic Thermoplastic Starch Composites to Fabricate Antifogging Sustainable Films with High Antibiosis and Transparency

Fogging on transparent surfaces such as goggles causes a series of hazards to users. To fabricate antifogging and low-haze transparent renewable polymer materials, intrinsic hydrophilicity with high water adsorption capability of thermoplastic starch (TPS) had been adopted. Strikingly, when benzoic acid (BA) was blended with thermoplastic starch (TPS-BA), the haze of TPS-BA was only 7.8% when it suffered the cold and warm method of antifogging measurement with 87% transmittance. Simultaneously, TPS-BA achieved an 18 mm inhibition zone for Staphylococcus aureus. To reveal the antifogging mechanism of TPS-BA films, the surficial and interior structure features were evaluated by three-dimensional optical scanner, scanning electron microscopy (SEM), contact angle testing, small-angle X-ray scattering (SAXS), X-ray diffraction (XRD), temperature-dependent Fourier transform infrared (FTIR), dynamic mechanical analysis (DMA), and so on. The incorporation of BA resulted in the roughness (Rq), water contact angle (WCA), and crystallinity of the TPS-BA film decreasing from 6.5 to 0.68 μm, 65.1 to 39.9°, and 13.6 to 6.3%, respectively. The amorphous matrix and smooth surface reduced the scattered light, allowing the TPS-BA film to achieve low haze performance and high transmittance. Importantly, the diversified and weakened hydrogen bonds formed among starch, BA, and glycerol could inhibit the formation of starch crystalline regions and allowed hydroxyl groups to quickly bond with water. Thus, when TPS-BA is placed in a high-humidity surrounding, an "expressway"is constructed for water molecules diffusing into the TPS-BA matrix. This novel low-haze, antifogging, sustainable, and facilely fabricated TPS with antibacterial properties is a promising candidate in disposable medical goggles to fight against COVID-19. © 2021 American Chemical Society. All rights reserved.

Amphiphilic Janus Microspheres Prepared by Caged Photoactivatable Alkoxysilane

A simple photolysis route was proposed to prepare Amphiphilic Janus Particles (AJP) based on SiO2 microspheres. The surface of SiO2 microspheres were modified by photoactive alkoxysilane, which was synthesized by dealcoholization condensation of 6-nitroveratroyloxycarbonyl and isocyanatopropyl-triethoxysilane. UV irradiation caused eater-breaking allowed for the precise control of hydrophilic modification of the hemispherical exposed particles surfaces. The component and morphology of the obtained particles were characterized by fourier transform infrared spectroscopy and ultraviolet-visible spectroscopy, and the Janus feature was evaluated by scanning electron microscopy, transmission electron microscopy, and dispersity in the oil–water dual-phases. The following results were obtained. The AJP with 450 nm size processes the hydrophilic amino groups on one side and the hydrophobic 6-nitroveratryloxycarbonyl moieties on the other. Additionally, the AJP were located at the phase boundary between water and n-hexane, and the negative charged gold nanoparticles with 25 nm size were adsorbed only onto the side with the positive charged amino groups. The AJP have interfacial adsorption energies that can be as much as three times larger than that of homogeneous particles and thus exhibit excellent surface activities.

Remdesivir extraction by extracorporeal life support circuits

INTRODUCTION: Many patients with severe COVID-19 require extracorporeal membrane oxygenation (ECMO) and/or continuous renal replacement therapy (CRRT), both of which can alter drug disposition. Lipophilic, highly protein bound drugs can adsorb to circuit materials, while hydrophilic, minimally protein bound drugs are likely to be filtered. HYPOTHESIS: Remdesivir (RDV) is lipophilic and highly protein bound making it likely to be adsorbed by circuit components and minimally cleared by hemofiltration/dialysis. RDV's active metabolite GS-441524 is hydrophilic and minimally protein bound and should be minimally adsorbed but rapidly filtered. METHODS: We administered RDV and GS-441524 to blood-primed, closed loop, ex vivo ECMO and CRRT circuits and measured drug concentrations over time. Drugs were also administered to a separate control tube to determine drug degradation. Each experiment was performed in triplicate. Drug recovery (%) was calculated by dividing each concentration by the initial concentration. RESULTS: Mean (standard deviation) recovery of RDV in the ECMO circuits (n=3) was low at 33.3% (2.0) at 6 hours. Recovery in the control (n=3) at 6 hours was 29.3% (2.0) and not significantly different from recovery in the ECMO circuits at 6 hours (p=0.07). Substantial loss of RDV in the CRRT circuits (n=3) occurred within minutes. Recovery was 14.4% (5.7) at 5 minutes and 4.7% (1.0) at 3 hours and significantly different compared to control recovery at 3 hours (p=0.008). Recovery of GS-441524 was higher than RDV in the ECMO circuits (n=3). After 6 hours, recovery was at 75.8% (16.5). Mean recovery in the control (n=3) at 6 hours was 70.6% (6.2) and not significantly different from recovery in the ECMO circuit at 6 hours (p=0.7). In the CRRT circuits (n=3), GS-441524 recovery was low at 15.9% (3.0) at 30 minutes and 0% (0) at 3 hours and significantly different from the control (p=0.005). CONCLUSIONS: RDV is extracted by ECMO and CRRT primarily by drug adsorption to circuit materials and potentially by drug metabolism in the blood. GS-441524 was not substantially extracted by the ECMO circuit but rapidly cleared by hemodiafiltration in the CRRT circuit. The extent of loss for both molecules, especially in CRRT, suggests that in patients supported with ECMO and CRRT, dosing adjustments are needed.

Paralytic tachyphylaxis and ECMO

INTRODUCTION: Critically ill adult patients requiring extracorporeal membrane oxygenation (ECMO) with prolonged paralytic exposure may develop potential tachyphylaxis. This phenomenon has yet to be described within the ECMO literature. DESCRIPTION: A 49-year-old male (70 kg) with hyperlipidemia and recently diagnosed COVID19, was admitted to the ICU for acute respiratory distress syndrome, intubated and paralyzed, and subsequently initiated on VV ECMO. By day 20, his sedation and paralytic regimen consisted of the following: hydromorphone 6 mg/hr, midazolam 12 mg/hr, phenobarbital IV 120 mg twice daily, and cisatracurium 12 mcg/kg/min, which was gradually increased from 5 mcg/kg/min from the previous 7 days. Propofol use was limited because of hypertriglyceridemia. Despite this, he was dyschronous with the ventilator and had 4/4 twitches on a train of four (TOF), with stable hemodynamics. A recommendation was made to stop cisatracurium and switch to rocuronium given concern for paralytic tachyphylaxis. The cisatracurium drip was stopped and the patient was loaded with a 1.2 mg/ kg (85 mg) rocuronium bolus using total body weight (TBW), followed by an 8 mcg/kg/min infusion. After 24 hours of use, the patient was more synchronous, had 0/4 twitches on a TOF, and did not require any escalation in the rocuronium infusion rate. This effect persisted for several days thereafter. DISCUSSION: This case highlights the phenomenon of paralytic tachyphylaxis in the ECMO population and sheds light on pharmacokinetic (PK) considerations. While the specific mechanism of resistance is not clearly understood, case reports in non-ECMO patients suggest that the likelihood of tachyphylaxis increases with high doses (≥12 mcg/kg/min) and prolonged use (> 7 days). Management included stopping the initial paralytic and switching to an alternative agent. Rocuronium is a hydrophilic drug with limited protein binding. Given this PK profile, we anticipated that the degree of sequestration in the ECMO circuit would be relatively low. Following our experience, we concluded that the switch to rocuronium was safe and effective in minimizing tachyphylaxis. Dosing of rocuronium may be similar to non- ECMO patients and should be guided by ventilator synchrony and TOF monitoring.