Subject-Based versus Population-Based Care after Radiation Exposure

Abstract

In a mass casualty radiation event situation, individualized therapy may overwhelm available resources and feasibility issues suggest a need for the development of population-based strategies. To investigate the efficacy of a population-based strategy, Chinese macaques (n = 46) underwent total-body irradiation and received preemptive antibiotics, IV hydration on predetermined postirradiation days and were then compared to macaques (n = 48) that received subject-based care in which blood transfusions, IV hydration, nutritional supplementation and antibiotic supportive measures were provided. Estimated radiation doses for LD30/60, LD50/60 and LD70/60 of animals with subject-based care: 6.83 Gy (6.21, 7.59), 7.44 Gy (6.99, 7.88) and 8.05 Gy (7.46, 8.64), respectively, and for population-based care: 5.61 Gy (5.28, 6.17), 6.62 Gy (6.13, 7.18) and 7.63 Gy (7.21, 8.20), respectively. Analysis of four time periods, 0-9, 10-15, 16-25 and 26-60 days postirradiation, identified significant mortality differences during the period of 10-15 days. A subset analysis of higher radiation doses (6.75-7.20 Gy, n = 32) indicated hydration, nutrition and septic status were not significantly different between treatments. Whole blood transfusion treatment, administered only in subject-supportive care, was associated with significantly higher platelet and absolute neutrophil counts. Median platelet counts greater than 5,670 cells/μl and absolute neutrophil counts greater than 26 cells/μl during this period correlated with survival. We observed that the population-based treatment increased the LD50/60 compared to nontreatment (6.62 Gy vs. 4.92 Gy) and may be further optimized during days 10-15, where strategic blood transfusions or other strategies to achieve increases in neutrophil and platelet counts may further increase survival rates in subjects exposed to high doses of radiation.

Combined Hydration and Antibiotics with Lisinopril to Mitigate Acute and Delayed High-dose Radiation Injuries to Multiple Organs

“…This evidence also supports our contention that ARS following 13 Gy leg-out PBI is primarily due to GI toxicity. As with humans (Anno et al 2003) and non-human primates (Yu et al 2015), this study shows that saline hydration and antibiotics improved survival in rats after leg-out PBI. However, the primate studies were done without bone marrow sparing and therefore involved much lower doses of irradiation (<10 Gy).…”

“…The LD 50 (radiation dose resulting in 50% death) increased from 4.1 Gy at Nagasaki (n=75, (Levin et al 1992)) to 8.9 Gy at Chernobyl (n=238, (Anno et al 2003)) which was largely ascribed to the use of intensive supportive care. In non-human primates (Chinese Macaques) population-based supportive care improved the LD 50 from 4.9 Gy to 6.6 Gy (Yu et al 2015), while symptom-based supportive care that included blood transfusion increased the LD 50 to 7.4 Gy (Yu et al 2015). In primate studies and in the clinic, steroids have also been used to manage symptoms of radiation pneumonitis (Yu et al 2015, Garofola et al 2014 a & b, Geraci et al1992, Gross 1980, Gross et al 1988).…”

“…In non-human primates (Chinese Macaques) population-based supportive care improved the LD 50 from 4.9 Gy to 6.6 Gy (Yu et al 2015), while symptom-based supportive care that included blood transfusion increased the LD 50 to 7.4 Gy (Yu et al 2015). In primate studies and in the clinic, steroids have also been used to manage symptoms of radiation pneumonitis (Yu et al 2015, Garofola et al 2014 a & b, Geraci et al1992, Gross 1980, Gross et al 1988). Although few studies have addressed the effect of supportive care on DEARE, indirect evidence from accidents (e.g.…”

White Matter is the Predilection Site of Late-Delayed Radiation-Induced Brain Injury in Non-Human Primates

“…Irradiation procedures for control comparators and animals receiving fWBI are described elsewhere (35), and further details about fWBI are provided by Hanbury et al (12) and Robbins et al (36). The irradiation procedure for animals receiving TBI is described by Yu et al (38).…”

“…Total-body irradiated animals received 6.75-8.05 Gy (median: 7.2 Gy; range: 6.75-8.05 Gy) administered via a 6-MV LINAC at a nominal dose rate of 0.8 6 0.025 Gy/min. Fifty percent of the dose was delivered from the anterior-posterior direction, and the remaining dose was delivered from the posterior-anterior direction (38).…”