Effects of prolonged nitrous oxide exposure on hemopoietic stem cells in mice

The effects of prolonged exposure to nitrous oxide on the hemopoietic progenitor cells in bone marrow and spleen in mice were investigated. Fifty percent nitrous oxide caused a marked decrease in the number of pluripotent stem cells (CFU-S) and granulocyte-macro-phage progenitor cells (GM-CFC) in the spleen, whereas it caused only a slight decrease in these cells in the bone marrow. These results suggest that prolonged exposure to nitrous oxide induces damage in the splenic hemopoiesis in mice.(Konno M et al.: Effects of prolonged nitrous oxide exposure on hemopoietic stem cells in mice. J Anesth 1: 29–34, 1987)     

Prolonged nitrous oxide exposure inhibits settlement of transplanted hemopoietic stem cells in murine spleen

In order to clarify the mechanism of hemopoietic depression induced by nitrous oxide inhalation, effects of prolonged nitrous oxide exposure on the settlement of transplanted bone marrow cells were investigated. Mice were continuously exposed to mixed gas containig 50% nitrous oxide, 21% oxygen and 29% nitrogen for 7 days and then they were irradiated with 850 rads. By the irradiation, endogenous pluripotent hemopoietic stem cells (CFU-S) almost disappeared in the mice. Normal syngenic murine bone marrow cells were injected intravenously and the numbers of CFU-S, which settled in the bone marrow and spleen 2hr after injection, were measured. There was no difference of the numbers of CFU-S settled in the bone marrow between nitrous oxide and control gas exposed mice. In contrast, the numbers of CFU-S in the spleen of nitrous oxide exposed mice were approximately 60% of the control. These results and our previous data suggest that hemopoietic inhibitory effects of nitrous oxide in mice are due to a damage of splenic hemopoietic microenvironment, that supports the settlement of hemopoietic stem cells.(Suzuki K, Kirikae T, Konno M et al.: Prolonged nitrous oxide exposure inhibits settlement of transplanted hemopoietic stem cells in murine spleen. J Anesth 3: 43–47, 1989)     

Increased lethality and delay in the recovery of hemopoietic stem cells after irradiation in mice exposed to nitrous oxide

Effects of N₂O–exposure on the survival rate and growth kinetics of hemopoietic stem cells after irradiation were investigated. LD 50, 30 days after irradiation, was 300 rad for N₂O exposed mice and over 550 rad for control mice. Recovery of the pluripotent hemopoietic stem cells (CFU–S) and granulocyte–macrophage progenitor cells (GM–CFC) was significantly delayed in the spleen of N₂O–exposed mice after 150 rad irradiation, compared to that of control mice. However, in bone marrow, there was a significant but slight difference in the recovery of GM–CFC and no significant difference in the recovery of CFU–S between the two groups. These results suggest that N₂O augments the damage of splenic hemopoiesis in irradiated mice, and this may be responsible for the increased hemopoietic death.     

Effect on outcome of prolonged exposure of patients to nitrous oxide

Prolonged (several days or repeated) exposure to nitrous oxide (N2O) can cause injury or death. To assess whether relatively prolonged anesthesia with N2O in normal patients might similarly cause untoward effects, we investigated whether the addition of N2O to isoflurane anesthesia caused injury to patients having surgical resection of acoustic neuroma lasting approximately 10 h. Twenty-six patients undergoing surgical resection of acoustic neuroma were randomly assigned to a regimen that included or excluded N2O (50%-60%) during isoflurane anesthesia plus intravenous adjuvants. On average, slightly less isoflurane (0.24%) was used during anesthesia with N2O. We measured standard clinical variables (blood pressure, heart rate), oxygen saturation, neurologic status, pain, and the incidence and type of morbid outcomes. Exposure to N2O did not increase the incidence of morbid outcomes (including hepatic injury, infection, or hypoxemia), prolong hospitalization, or increase common postoperative complaints such as nausea, vomiting, coughing, or headache. Patients anesthetized with either regimen were equally satisfied with their anesthetic.     

Testicular reaction to prolonged exposure to nitrous oxide.

Male LEW/f Mai rats were exposed to an atmosphere of 20 per cent N2O, 20 per cent O2, and 60 per cent N2 for a maximum of 35 days. Evidence of injury to the seminiferous tubules was found in some animals by the second day. By 14 days, such damage was found in all animals. The toxic effect was confined to the spermatogenic cells, with consequent reduction in mature spermatozoa and appearance of multinucleated forms. Other cells within the testes were resistant to damage. Recovery of spermatogenesis occurred after return to room air for more than three days. Serum testosterone levels were not significantly affected during the prolonged exposure.     

Effects of nitrous oxide on MAC

The minimal alveolar concentration (MAC) is defined as the end-expiratory concentration of an inhalational anaesthetic that is required to suppress gross purposeful movement to a painful stimulus in 50% of subjects. The MAC of nitrous oxide is 1·04 atmospheres absolute (corresponding to 104 vol%). The MAC criterion has served since the early 1960s as a gold standard to compare the relative potencies of inhalational anaesthetics. Since more recent studies have demonstrated that determining the MAC measures an anaesthetic effect localized at the spinal cord and being independent from anaesthetic action at the brain the clinical relevance of MAC values are questioned. However, there is still no commonly accepted substitute to the MAC for comparing the relative potencies of inhalational and intravenous anaesthetics and related drugs.     

Carcinogen bioassay of nitrous oxide in mice

A carcinogen bioassay of nitrous oxide (N2O) was performed in groups of male and female Swiss-Webster mice exposed to either air (n = 179), 10% N2O (n = 152), or 40% N2O (n = 151) for 4 h per day, 5 days per week. After 78 weeks of exposure, there was a 5-week period without treatment following which surviving mice were killed. Mice killed at this time or dying in extremis at other times were subjected to complete autopsy unless advanced autolysis or cannibalism precluded examination. Mean body weights for male and female mice in the 10% N2O group were the same as those in the air control group throughout the study, whereas they were 5% less in the 40% N2O group. Mean organ weights for N2O-treated mice were not statistically different from those of control mice. Gross and microscopic examination of tissues revealed a variety of neoplastic and nonneoplastic lesions; however, their presence was unrelated to treatment.     

Occupational exposure to nitrous oxide in four hospitals

Diffusive samplers were used to measure the exposure of the anaesthetist, anaesthetic assistant and circulating nurse to nitrous oxide in every operating theatre of four Glasgow hospitals. Each theatre was surveyed over 1 or 2 weeks; samples were taken during every operating session. The exposures were in general surprisingly high. The anaesthetist's exposure was greater than ppm on about half the occasions. The study underlines the need for theatre ventilation systems and scavenging equipment to be properly maintained and for scavenging facilities to be used effectively. It is concluded that regular monitoring of staff exposures is required to check the effectiveness of antipollution measures.     

Age-dependent alterations in nitrous oxide requirement of mice

To determine the relationship of nitrous oxide requirement to age in mice, the authors repeatedly tested the righting-reflex response in stock CD-1 mice at 50 to 703 days of age. Over this age range, nitrous oxide requirement (+/- SE) progressively decreased from 1.48 +/- 0.02 atm to 1.09 +/- 0.06 atm. A second set of experiments measured changes in nitrous oxide requirement with age in mice selectively bred for resistance (HI mice) and susceptibility (LO mice) to nitrous oxide anesthesia. When tested at two months of age, selected HI and LO mice had nitrous oxide ED50 values of approximately 2.0 and 1.1 atm, respectively. At 11 to 14 months, the nitrous oxide ED50 of the HI mice had decreased to approximately 1.5 atm. In contrast, the nitrous oxide ED50 of the LO mice showed a much smaller decrease over this age range. Thus, the separation in nitrous oxide requirement between the HI and LO lines tended to disappear with age. By correlating the difference in anesthetic requirement between the HI and LO mice with biochemical and biophysical alterations in the central nervous system, studies on aging that use selectively bred lines may be helpful in investigating the mechanism of anesthetic action and the mechanism by which aging affects anesthetic action.     

Occupational exposure to nitrous oxide and desflurane during ear-nose-throat-surgery

PURPOSE: To determine occupational exposure of the anesthesiologist and surgeon to nitrous oxide and desflurane during general anesthesia for ear-nose-throat (ENT) surgery in children and adults. METHODS: An observational clinical trial was performed in ten children (C) and ten adults (A). Tracheas were intubated, in adults, with cuffed tubes and in children with uncuffed tubes. The operating room was equipped with modern air conditioning and waste anesthetic gas scavengers. Gas samples were obtained during the operative procedure every 90 sec from the breathing zone of subjects. Time-weighted averages (TWA) over the time of exposure were calculated for nitrous oxide and desflurane. RESULTS: Nitrous oxide TWAs for anesthesiologists were 0.41 +/- 0.23 ppm (A) and 1.20 +/- 0.32 ppm (C, P < 0.0001), and 2.24 +/- 1.93 ppm (A) and 5.30 +/- 0.60 ppm (C, P = 0.0001) for the surgeon who worked close to the patient's airway and thus had higher exposure (P < 0.05 [A], P < 0.0001 [C]). With regard to desflurane, the anesthesiologists' TWAs were 0.02 +/- 0.03 ppm for both adults and children. The surgeon was exposed to 0.21 +/- 0.24 ppm desflurane (A) and 0.30 +/- 0.14 ppm (C, P: n.s.). Although the surgeon's exposure was greater (P < 0.05 [A], P < 0.0001 [C]), the threshold limits of 25 ppm for nitrous oxide and 2 ppm for desflurane recommended by the National Institute of Occupational Safety and Health were not exceeded. CONCLUSIONS: Under modern air conditioning, occupational exposure to inhalational anesthetics is low, and inhalational anesthesia is safe from the standpoint of modern workplace laws and health-care regulations.