Halothane and isoflurane enhance melanoma tumour metastasis in mice.

PURPOSE: To investigate the incidence of tumour metastasis from B16 melanoma tumour cells in experimental animals following exposure to equipotent concentrations of halothane or isoflurane, and to differentiate if exposure to one anaesthetic resulted in greater metastases than the other. METHODS: Experimental animals (C57B1 mice), were randomized to receive 1.3 MAC hours of halothane or isoflurane anaesthesia. The control group of animals received oxygen alone under identical conditions. Fifteen minutes after completion of anaesthesia, control and experimental groups were given 1 x 10(5) B16 melanoma cells intravenously. After 21 days, all animals were autopsied, and the metastatic nodules in their lungs were counted. The difference in the numbers of metastatic nodules between control and experimental groups of animals was analyzed for significance by the Mann Whitney "U test". RESULTS: More metastases were observed in the animals exposed to halothane (37.28 +/- 5.08, P < 0.0001), or isoflurane anaesthesia (28.24 +/- 4.07, P < 0.0014) than in the control animals (12.22 +/- 1.52). CONCLUSION: Exposure to halothane or isoflurane anaesthesia increased the number of pulmonary metastases in C57B1 mice compared with the control groups but there was no difference in metastases among animals treated with halothane or isoflurane.

Intramuscular cimetidine and ranitidine as prophylaxis against gastric aspiration syndrome--a randomized double-blind study.

Preoperative cimetidine 300 mg or ranitidine in 50 and 100 mg doses were administered intramuscularly to 120 patients in a randomized double-blind study. The volume and pH of gastric aspirate samples obtained after tracheal intubation and before extubation were measured. The pH of gastric aspirate was higher following ranitidine 100 mg than ranitidine 50 mg or cimetidine 300 mg at both intubation and extubation (p = 0.006). In addition, fewer patients tended to be "at risk" of pulmonary aspiration syndrome (pH less than or equal to 2.5) after ranitidine 100 mg than ranitidine 50 mg or cimetidine 300 mg. Preoperative intramuscular ranitidine 100 mg was found to be suitable for use in protection against gastric aspiration syndrome.

Comparative effects of volatile anaesthetic agents and nitrous oxide on human leucocyte chemotaxis in vitro.

Infection following surgery is not uncommon. Human leucocytes play a vital role in the body's defense against infection. In order to decrease perioperative morbidity and mortality from infection, it is important to define the comparative effects of different anaesthetic agents on the leucocyte function. Therefore, the effect of equipotent concentrations (MAC 1) of isoflurane, enflurane, halothane, methoxyflurane and 70 per cent nitrous oxide, on the leucocyte chemotactic migration was investigated in vitro. The chemotactic migration of neutrophils and monocytes, with and without equilibration with MAC 1 concentrations of different volatile anaesthetics and 70 per cent nitrous oxide, was compared by using a modification of Boyden's method. Chemotactic migration of both cell types was unaffected by isoflurane, but a significant depression of chemotactic migration was observed with enflurane, halothane, methoxyflurane and nitrous oxide (p less than 0.05). The severity of depression of migration was maximal with nitrous oxide, followed by methoxyflurane, halothane and enflurane in order. It is concluded that equipotent concentrations of various anaesthetic agents produce different degrees of depression of leucocyte chemotactic migration in vitro.

A double-blind comparison of cimetidine and ranitidine as prophylaxis against gastric aspiration syndrome.

Preoperative cimetidine, ranitidine, or placebo were administered, orally or intravenously to 190 patients in a double-blind study. The volume and pH of gastric aspirate samples, obtained after tracheal intubation and before extubation, were measured. Both cimetidine and ranitidine produced higher mean pH levels and thus fewer patients "at risk" should gastric aspiration occur (pH less than or equal to 2.5) than did placebo. Intravenous ranitidine (in both 40- and 80-mg doses) produced fewer patients at risk in the event gastric aspiration should occur than did cimetidine, 300 mg, and the 80-mg dose produced a higher mean pH level. Oral ranitidine, 150 mg, produced a significantly higher mean pH level than did oral cimetidine, 300 mg, and tended to give fewer patients at risk. The volumes of gastric contents aspirated were similar following each of the drugs except that the volume was significantly less two hours following oral ranitidine, 150 mg, than after oral cimetidine, 300 mg.

Influence of anaesthesia and surgery on neutrophil chemotaxis.

Chemotactic migration of leucocytes is one of the earliest and essential events among the host defense mechanisms against infection. Therefore, the influence of anaesthesia and surgery on leucocyte chemotaxis was investigated in patients requiring elective surgery. The chemotactic migration of peripheral blood leucocytes was measured by a modification of Boyden's method immediately before and after operation and on the second and third postoperative days. In addition, the influence of exposure to different molar concentrations of thiopentone on chemotactic migration was investigated in vitro. A statistically significant inhibition of leucocyte chemotactic migration was observed in the immediate postoperative period. (P less than 0.05). However, this inhibition was of short duration and chemotactic activity returned to normal on the day after operation under general anaesthesia. Exposure to thiopentone produced a significant and dose dependent inhibition of chemotactic migration in vitro. It is concluded that surgery under general anaesthesia and exposure to thiopentone in vitro produce a significant though reversible inhibition of chemotactic migration of leucocytes.

Inhibition, by anaesthetic agents, of human leucocyte locomotion towards chemical attractants.

The effects of local, i.v. and volatile anaesthetic agents on locomotion of human blood leucocytes were studied in vitro. Blood neutrohpils and monocytes and PHA-activated lymphocytes were allowed to migrate in filters towards standard chemotactic agents and the effect of adding anaesthetic agents to the system was measured. The results showed that locomotion of all cell types was depressed reversibly by all classes of anaesthetics used at clinical concentrations. The pattern of depression varied according to the cell type under study and the class of anaesthetic used. The action of anaesthetics on chemically stimulated locomotion of leucocytes was analysed. It was concluded that the principal action of these drugs is primarily on the mechanism of locomotion itself, rather than on the capacity of the cells to detect and respond to concentration gradients of attractants. Serum albumin can protect against the inhibitory action of anaesthetics.

Post-operative depression of antibody-dependent lymphocyte cytotoxicity following minor surgery and anaesthesia.

Leucocytes taken 1 day post-operatively from patients who had undergone surgery under general anaesthesia for benign breast disease showed a significantly diminished capacity to induce lysis of antibody-coated target cells compared with those taken pre-operatively from the same patients. No significant fall in PHA responsiveness was observed in these leucocytes in the post-operative period. This indicates a high sensitivity of the cell types involved in the antibody-dependent cell-mediated cytotoxicity reaction to the suppressive effect of surgery and anaesthesia. Plasmas taken post-operatively from these patients were effective in diminishing the capacity of leucocytes from healthy untreated donors to initiate antibody-coated target cell lysis compared with pre-operative plasmas although the plasma cortisol levels in these samples did not differ significantly. Possible mediators of this suppressive effect and its significance are discussed.

Effect of surgery on tumour-directed leucocyte responses.

Leucocytes from 22 out of 26 patients with mammary carcinoma were significantly cytotoxic in vitro for cells cultured from mammary tumours though only two out of 17 of these preparations were cytotoxic for cells cultured from tumours arising at other sites. In the immediate postoperative period reactivity of patients' leucocytes with mammary tumour cells was undetectable but returned within one week of surgery. Leucocyte cytotoxicity may therefore offer a model in which the mechanism of postoperative depression of immunological competence may be investigated.