ABSTRACT
INTRODUCTION: The optimal modality for renal replacement therapy (RRT) in patients venoarterial extracorporeal membrane oxygenation (VA-ECMO) remains unclear. This study aimed to compare outcomes between continuous renal replacement therapy (CRRT) and peritoneal dialysis (PD) in VA-ECMO patients. METHODS: This single-center retrospective study included VA-ECMO patients who developed AKI and subsequently required CRRT or PD. Data on patient demographics, comorbidities, clinical characteristics, RRT modality, and outcomes were collected. The primary outcome was in-hospital mortality, with secondary outcomes including length of stays, RRT durations, and complications associated with RRT. RESULTS: A total of 43 patients were included (72.1% male, mean age 58.2 ± 15.7 years). Of these, 21 received CRRT and 22 received PD during ECMO therapy. In-hospital mortality rates did not significantly differ between CRRT and PD groups (80.9% vs 90.9%, p = 0.35). However, PD was associated with a higher incidence of catheter-related complications, including malposition (31.8% vs 4.7%, p = 0.046), infection (22.7% vs 4.7%, p = 0.19), and bleeding (18.2% vs 9.5%, p = 0.66), respectively. CONCLUSION: Among patients receiving VA-ECMO-supported RRT, our study revealed comparable in-hospital mortality rates between CRRT and PD, although PD was associated with a higher incidence of catheter-related complications.
Subject(s)
Acute Kidney Injury , Continuous Renal Replacement Therapy , Extracorporeal Membrane Oxygenation , Hospital Mortality , Peritoneal Dialysis , Humans , Male , Female , Middle Aged , Extracorporeal Membrane Oxygenation/adverse effects , Extracorporeal Membrane Oxygenation/mortality , Extracorporeal Membrane Oxygenation/methods , Retrospective Studies , Peritoneal Dialysis/methods , Acute Kidney Injury/therapy , Acute Kidney Injury/mortality , Aged , Length of Stay , Treatment Outcome , AdultABSTRACT
The detachable dissolving microneedles (DDMNs) feature an array of needles capable of being separated from the base sheet during administration. Here they were fabricated to address delivery efficiency and storage stability of insulin. The constructed insulin-DDMN is multi-layered, with 1) a hard tip cover layer; 2) a layer of regular short-acting insulin (RI) mixed with hyaluronic acid (HA) and sorbitol (Sor) which occupies the taper tip region of the needles; 3) a barrier layer situated above the RI layer; and 4) a fast-dissolving layer connecting the barrier layer to the base sheet. RI entrapped in DDMNs exhibited enhanced thermal stability; it could be stored at 40 °C for 35 days without losing significant biological activity. Differential scanning calorimetric analysis revealed that the HA-Sor matrix could improve the denaturation temperature of the RI from lower than room temperature to 186 °C. Tests in ex vivo porcine skin demonstrated RI delivery efficiency of 91±1.59 %. Experiments with diabetic rats revealed sustained release of RI, i.e., when compared to subcutaneous injection with the same RI dose, RI-DDMNs produced slower absorption of insulin into blood circulation, delayed onset of hypoglycemic effect, longer serum insulin half-life, and longer hypoglycemic duration.
Subject(s)
Diabetes Mellitus, Experimental , Drug Stability , Hypoglycemic Agents , Needles , Animals , Rats , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/blood , Swine , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/pharmacokinetics , Hypoglycemic Agents/chemistry , Drug Delivery Systems/methods , Drug Delivery Systems/instrumentation , Rats, Sprague-Dawley , Insulin, Short-Acting/administration & dosage , Insulin, Short-Acting/pharmacokinetics , Insulin, Long-Acting/administration & dosage , Insulin, Long-Acting/pharmacokinetics , Male , Hyaluronic Acid/chemistry , Hyaluronic Acid/administration & dosage , Temperature , Administration, Cutaneous , Skin/metabolism , Insulin/administration & dosage , Insulin/pharmacokinetics , Sorbitol/chemistry , Microinjections/methods , Microinjections/instrumentation , Injections, Subcutaneous , Delayed-Action PreparationsABSTRACT
Although vaccine administration by microneedles has been demonstrated, delivery reliability issues have prevented their implementation. Through an ex vivo porcine skin experiment, we show visual evidence indicating that detachable dissolvable microneedles (DDMN) can deposit cargo into the dermis with insignificant loss of cargo to the stratum corneum. Using ovalbumin (OVA), a model antigen vaccine, as a cargo, the ex vivo experiments yielded a delivery efficiency of 86.08 ± 4.16 %. At room temperature, OVA could be stabilized for up to 35 days in DDMN made from hyaluronic acid and trehalose. The DDMN matrix could improve the denaturation temperature of the OVA from around 70-120 °C to over 150 °C, as demonstrated by differential scanning calorimetric analysis. In vivo delivery of OVA antigen into the mice's skin via DDMN elicited 10 times higher specific antibody responses compared to conventional intramuscular injection. We envision DDMN as an effective, precise dosing, intradermal vaccine delivery system that may require no cold-chain, offers a dose-sparing effect, and can be administered easily.