Abstract
BackgroundExtracorporeally induced whole‐body hyperthermia (eWBH) might be a beneficial treatment in cancer patients. Objectives of this pig study were to assess thermal distribution, (patho‐)physiological effects, and safety of eWBH with a new WBH device.MethodsFourteen healthy adult pigs were anesthetized, mechanically ventilated, and cannulated; 12 were included in the analysis. Blood was heated in 11 pigs (one pig served as control) using a WBH device (Vithèr Hyperthermia B.V.) containing two separate fluidic circuits and a heat exchanger. Temperature was monitored on nine different sites, including the brain. Core temperature (average of 4 deep probes) was elevated to 42°C for 2 hr.ResultsElevation of core body temperature to 42°C took on average (± standard deviation) 38 ± 8 min. Initially observed temperature spikes diminished after lowering maximal blood temperature to 45°C. Hereafter, brain temperature spikes never exceeded 42.5°C, mean brain temperature was at highest 41.9°C during maintenance. WBH resulted in increased heart rates and decreased mean arterial pressures. The vast amounts of fluids required to counter hypotension tended to be smaller after corticosteroid administration. Hemodialysis was started in three animals (potassium increase prevention in two and hyperkalemia treatment in one). Severe rhabdomyolysis was observed in all pigs (including the control). All animals survived the procedure until planned euthanasia 1, 6, or 24 hr post procedure.ConclusionFast induction of eWBH with homogenous thermal distribution is feasible in pigs using the Vithèr WBH device. Severe hemodynamic disturbances, rhabdomyolysis, and hyperkalemia were observed.
Highlights
Synergism between the beneficial effects of local or regional hyperthermia combined with chemotherapy and radiotherapy has been proven in numerous clinical studies (Datta et al, 2015; Issels, 2008; Peeken, Vaupel, & Combs, 2017) Recently, in a phase III study advantages of regional hyperthermia in combination with chemotherapy on long-term outcomes have been demonstrated in patients with high-risk soft tissue sarcoma
In the first four animals blood was heated to 48°C, which led to high-temperature peaks on several organ sites shortly after reaching the core body temperature of 42°C
2011; Zwischenberger et al, 2001) models hemodynamic changes are observed during Extracorporeally induced whole-body hyperthermia (eWBH) treatment
Summary
Synergism between the beneficial effects of local or regional hyperthermia combined with chemotherapy and radiotherapy has been proven in numerous clinical studies (Datta et al, 2015; Issels, 2008; Peeken, Vaupel, & Combs, 2017) Recently, in a phase III study advantages of regional hyperthermia in combination with chemotherapy on long-term outcomes have been demonstrated in patients with high-risk soft tissue sarcoma. Controversial and never undisputedly confirmed, hyperthermia might be of benefit in patients with metastasized malignancies when whole-body hyperthermia (WBH) is applied To serve this purpose several techniques have been described to induce WBH: exogenous applied heat by submerging the body in hot fluids, radiant heating techniques, and heating the blood via extracorporeal circulation (eWBH) (Milligan, 1984; Vertrees, Leeth, Girouard, Roach, & Zwischenberger, 2002; Wust et al, 2002). It has unequivocally been proven that temperatures exceeding 43°C for more than 60 min lead to irreversible brain damage, so most of the studies on WBH aim at core body temperatures of maximal 41.8–42°C (Matsumi et al, 1994; Vertrees et al, 2002; Wust et al, 2002) Aiming at these temperatures, two studies with low number of patients proved the technique of veno-venous inducement of eWBH to be feasible (Locker et al, 2011; Zwischenberger et al, 2004). Objectives were to investigate the accuracy and efficacy of thermal dose delivery, to map the thermal distribution at various organs and to assess biochemical and hemodynamic disturbances when inducing eWBH at 42°C for 2 hr with the use of the Vithèr WBH device
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