The effects of anaesthetics on cisplatinum-induced toxicity at normal temperatures and during whole-body hyperthermia: the influence of NaCl concentration of the vehicle

Abstract

The effects of various anaesthetics, including a balanced combination of different anaesthetics (consisting of ketamine, xylazine, and acepromazine), Nembutal, and halothane anaesthesia on DDP-induced renal and intestinal toxicities at 37°C and at 41·5°C were studied using a F344 rat model. The combination anaesthesia decreased the DDP-induced lethality (LD₅₀) and toxic side-effects as evidenced by decreased in BUN and diarrhoea at day 5, whereas nembutal anaesthesia increased DDP-induced toxic side-effects at 37°C. The inhalation anaesthetic halothane had only minor influence on these DDP-induced toxicities.

Increasing the NaCl concentration of the DDP vehicle from 0·9 to 1·8 per cent decreased the DDP-induced toxicity both in non-anaesthetized and anaesthetized animals.

When applied simultaneously with DDP administration, whole-body hyperthermia (WBH; 120min at 41·5°C) increased the DDP-induced toxicity as indicated by the thermal enhancement ratio of between 2·1 and 2·7 for the LD₅₀ values. With combined WBH + DDP treatment the effect of anaesthetics on DDP-induced toxicities was generally similar to that observed at 37°C. The protective effects of the high NaCl (1·8 vs 0·9 per cent) concentration of the DDP vehicle, however, were minimal under hyperthermic conditions. The data suggest the need for caution in the use of DDP in combination with WBH.

Key Words:

• cisplatinum
• whole-body hyperthermia
• anaesthesia
• NaCl concentration
• renal toxicity
• gastrointestinal toxicity