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1.
Mil Med ; 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38421742

RESUMO

INTRODUCTION: United States Military operations in resource limited areas are increasing. Furthermore, future peer or near-peer conflicts will require caring for larger numbers of casualties with limited resources. In this setting, traditional renal replacement therapy is not feasible and novel methods are required to address severe acute kidney injury in austere environments lacking definitive therapies. Here, we describe experiments designed to determine the efficacy of a novel peritoneal packing material (Potassium Binding Pack-PBP, CytoSorbents INC) for the acute management of severe hyperkalemia. MATERIALS AND METHODS: Male swine (52 ±1 kg) were nephrectomized via midline laparotomy under a plane of anesthesia and randomized into one of two experimental groups (PBP & CON). Exogenous potassium was infused to achieve a serum potassium level of 7.5 mEq/L. Novel potassium absorbing packs (PBP) or sham packs (CON) were placed in the right and left upper quadrants, and the right and left paracolic gutters of the abdomen to simulate four-quadrant packing (n = 6, n = 5, respectively). Two liters of peritoneal dialysis fluid was instilled into the abdomen and temporary closure performed. Animals were observed for 12 hours. Serum and peritoneal fluid (dialysate) potassium levels were sampled at T = 15, 30, 60 min, and Q60min thereafter. Animals were humanely euthanized at the end of the observation period. RESULTS: Baseline characteristics were similar between groups. Pairwise analysis showed that serum potassium concentrations were significantly lower in the PBP group compared to CON at T = 540 and T = 720 (P = 0.006 and P = 0.015, respectively). Potassium concentrations were significantly lower in dialysate of the PBP group compared to CON at all time points after T = 15 (T = 30, P = 0.017; T = 60 through T = 720, P < 0.001). CONCLUSIONS: This is the first demonstration of an effective technology for the management of hyperkalemia in trauma in the absence of standard of care; renal replacement therapy. We identified that PBP was able to consistently maintain a concentration gradient between dialysate in the peritoneum and system potassium concentration throughout the experiment. Furthermore, systemic potassium concentrations were reduced in a clinically relevant manner in the PBP group compared to CON. This suggests that peritoneal packing technology for the management of metabolic disturbances in trauma has potential for clinical application. These results are preliminary and should be interpreted with caution.

2.
Sci Rep ; 10(1): 799, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964964

RESUMO

Mycotoxins, such as aflatoxin B1 (AFB1), pose a serious threat as biological weapons due to their high toxicity, environmental stability, easy accessibility and lack of effective therapeutics. This study investigated if blood purification therapy with CytoSorb (CS) porous polymer beads could improve survival after a lethal aflatoxin dose (LD90). The effective treatment window and potential therapeutic mechanisms were also investigated. Sprague Dawley rats received a lethal dose of AFB1 (0.5-1.0 mg/kg) intravenously and hemoperfusion with a CS or Control device was initiated immediately, or after 30, 90, or 240-minute delays and conducted for 4 hours. The CS device removes AFB1 from circulation and significantly improves survival when initiated within 90 minutes of toxin administration. Treated subjects exhibited improved liver morphology and health scores. Changes in the levels of cytokines, leukocytes and platelets indicate a moderately-severe inflammatory response to acute toxin exposure. Quantitative proteomic analysis showed significant changes in the level of a broad spectrum of plasma proteins including serine protease/endopeptidase inhibitors, coagulation factors, complement proteins, carbonic anhydrases, and redox enzymes that ostensibly contribute to the therapeutic effect. Together, these results suggest that hemoadsorption with CS could be a viable countermeasure against acute mycotoxin exposure.


Assuntos
Aflatoxina B1/intoxicação , Hemoperfusão/métodos , Fígado/efeitos dos fármacos , Micotoxicose/mortalidade , Micotoxicose/terapia , Aflatoxina B1/administração & dosagem , Aflatoxina B1/sangue , Aflatoxina B1/toxicidade , Animais , Contagem de Células Sanguíneas , Proteínas Sanguíneas/análise , Citocinas/sangue , Hemoperfusão/instrumentação , Dose Letal Mediana , Fígado/patologia , Micotoxicose/etiologia , Ratos Sprague-Dawley , Fatores de Tempo , Redução de Peso/efeitos dos fármacos
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