Thermal distribution, physiological effects and toxicities of extracorporeally induced whole-body hyperthermia in a pig model

Abstract

Background: Extracorporeally 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.

Methods: Fourteen 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.

Results: Elevation 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.

Conclusion: Fast induction of eWBH with homogenous thermal distribution is feasible in pigs using the Vithèr WBH device. Severe hemodynamic disturbances, rhabdomyolysis, and hyperkalemia were observed.

Keywords: extracorporeal circulation; hemodynamics; induced hyperthermia; safety; whole-body hyperthermia.

Figure 1

(a) Example of time–temperature curve at various locations with maximal blood heating temperature of 48°C. (b) Example of time–temperature curve at various locations with maximal blood heating temperature of 45°C. (c) Time–temperature curve of the core temperature in all pigs. (d) Time–temperature curve of the brain temperature in all pigs

Figure 2

Thermal distributions at various organs during maintenance phase of 11 pigs. Red line: target temperature

Figure 3

Scatterplot of individual observations of time to reach goal temperature sorted by groups with different maximal blood heating temperatures

Figure 4

Individual courses of heart rate and mean arterial pressure until 6 hr post procedure. Black margins: maintenance phase. Blue lines: without the administration of corticosteroids, red lines: with the administration of corticosteroids, yellow line: mean without the administration of corticosteroids, green line: mean with the administration of corticosteroids. Timepoints: t = 0: baseline, t = 1: start of heating, t = 2:15 min after start heating, t = 3: reaching 42°C, t = 4–11: every 15 min in the maintenance phase, t = 12–13:15 and 30 min after cooling started, t = 14: reaching 37°C, t = 15 and higher: hourly in the time post procedure

Figure 5

Serum creatine kinase levels during treatment and post procedure Timepoints: t = 0: baseline, t = 1: start of heating, t = 2:15 min after start heating, t = 3: reaching 42°C, t = 4–11: every 15 min in the maintenance phase, t = 12–13:15 and 30 min after cooling started, t = 14: reaching 37°C, t = 15 and higher: hourly in the time post procedure