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Biomedical subjects

R I Mazze

Publications and source records attributed to R I Mazze.

At least 19 recordsLinked to original sources

The effects of sevoflurane on serum creatinine and blood urea nitrogen concentrations: a retrospective, twenty-two-center, comparative evaluation of renal function in adult surgical patients.

UNLABELLED: Despite mounting clinical evidence that supports its safety, the question of the potential adverse effects of sevoflurane on renal function continues to generate some controversy. This study retrospectively evaluated pooled renal laboratory data from 22 different clinical trials that compared sevoflurane with three widely used anesthetics. The trials examined postoperative changes in serum creatinine and blood urea nitrogen levels from a total of 3, 436 ASA physical status I-IV adult surgical patients administered either sevoflurane (n = 1941) or a control drug (isoflurane, enflurane, or propofol; n = 1495) as the maintenance anesthetic. The incidences of increased serum creatinine and blood urea nitrogen concentrations were similar among patients administered sevoflurane and those administered control drugs. Additionally, no trends specific to sevoflurane were observed with respect to postoperative serum creatinine concentration and fresh gas flow rate, concurrent treatment with nephrotoxic antibiotics, or type of carbon dioxide absorbent. IMPLICATIONS: Our data for changes in serum creatinine and blood urea nitrogen indicate that, for exposures of less than 4 minimum alveolar anesthetic concentration/h, sevoflurane is not associated with an increased risk of renal toxicity compared with other commonly used anesthetics. For clinical purposes, the pre- to postoperative changes in serum creatinine and blood urea nitrogen are appropriate measures of renal function in surgical patients.

Adolescent↗

Trace nitrous oxide levels in the postanesthesia care unit.

UNLABELLED: The effect of trace levels of waste anesthetic gases on the health of postanesthesia care unit (PACU) nurses who work in an unscavenged environment has been questioned, although it seems likely that levels of trace gases in the PACU would be much lower than those in the operating room. In this study, we documented nitrous oxide levels in the ambient air of two large PACUs. Nitrous oxide levels were measured using a time-weighted average monitor worn by 33 PACU workers at two different hospitals for the duration of their shifts. On the same day, patient data were collected at the time of admission to the PACU. Data included age and weight of the patient, type of surgery, anesthetic technique, and end-tidal level of nitrous oxide immediately before the patient left the operating room. The mean time-weighted average nitrous oxide level in PACU A was 2.0 ppm (range 0-6.4); in PACU B, it was undetectable, i.e., < 2.0 ppm. Levels of nitrous oxide to which PACU patient care personnel are exposed are well below the National Institute of Occupational Safety and Health and Occupational Health and Safety Administration recommended exposure level of 25 ppm measured for the duration of anesthetic administration. IMPLICATIONS: Our results indicate that the levels of nitrous oxide in postanesthesia care units with well maintained, modern ventilation systems are very low. Previous research suggests that the health of workers exposed to these levels should not be adversely affected.

Air Pollutants, Occupational↗

Developmental toxicity of nondepolarizing muscle relaxants in cultured rat embryos.

Evidence of developmental toxicity of clinically used nondepolarizing muscle relaxants was sought in rat embryos grown in culture. Embryos were explanted at 8 AM on day 9 of gestation (presomite stage, plug day = day 0), and were cultured in rotating bottles with medium containing various concentrations of d-tubocurarine, pancuronium, atracurium, and vecuronium. At 10 AM on day 11 of gestation (forelimb bud stage), culture was terminated and embryos were examined for general morphology. Treatment with tested agents resulted in dose-dependent developmental toxicity; namely, growth retardation seen as decreased crown-rump length, decreased number of somite pairs, and morphologic abnormalities. However, the concentrations that caused toxicity were at least 30-fold greater than serum concentrations clinically achieved in the mother. We conclude that these muscle relaxants have a low potential for causing developmental toxicity during organogenesis.

Animals↗

Preventive effects of phenoxybenzamine on nitrous oxide-induced reproductive toxicity in Sprague-Dawley rats.

In previous studies, we have shown that the reproductive toxicity of N2O in rats is prevented by the co-administration of either halothane or isoflurane, whereas treatment with folinic acid, which should reverse the effects of N2O on DNA production, does not prevent toxicity. These results cast doubt on the commonly held theory that inactivation of methionine synthase is the sole cause of N2O-induced reproductive toxicity, and suggest the need for other hypotheses. One such possibility is that N2O causes adverse reproductive toxicity secondary to its sympathomimetic effects. As a first step to test this theory, we studied the effects of phenoxybenzamine (PX), an alpha-1 adrenergic antagonist, on N2O-induced reproductive toxicity using a well-established in vivo rat model. On day 8 of gestation (plug day = day 0), 130 timed-pregnant Sprague-Dawley rats were injected s.c. with either 0.5 ml of either 0.9% saline (control and N2O alone groups) or PX (0.5, 5, or 50 micrograms/kg) in 0.9% saline, the latter the maximum tolerated PX dose. They were then exposed to either air (control) or 60% N2O for 24 hours (all other groups). On day 20 of gestation, cesarean sections were performed and the fetuses were removed and examined for either visceral of skeletal abnormalities. Compared with control, treatment with N2O alone resulted in increased incidences of fetal resorptions, major and minor visceral abnormalities, and minor skeletal abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗

Adverse interaction between bupivacaine and halothane on ventricular contractile force and intraventricular conduction in the dog.

Regional anesthesia with bupivacaine in pediatric patients is often accompanied by light levels of halothane general anesthesia. To determine the potential cardiotoxicity of these two drugs when used together, we defined the interaction between moderate plasma bupivacaine concentrations (1270-1760 ng/mL) and halothane (end-tidal concentrations, 0.5%-1.0%) on ventricular contractility and conduction in 22 closed-chest dogs anesthetized with chloralose. Bupivacaine alone (1-mg/kg intravenous bolus plus a 0.1-mg.kg-1.min-1 constant rate infusion) resulted in significant increases in ventricular conduction time (VCT) and effective refractory period (VERP) and nonsignificant decreases in dP/dtmax and blood pressure. The addition of halothane resulted in hypotension and in progressively increasing plasma bupivacaine levels secondary to reduced hepatic clearance, which led to further dose-related significant increases in VCT and VERP and to significant decreases in dP/dtmax and blood pressure. In other dogs given halothane but in which bupivacaine levels were held constant (1400 ng/mL), VCT remained constant and VERP lengthened slightly, whereas dP/dtmax decreased. We conclude that the combination of bupivacaine and halothane can cause adverse effects on ventricular contractility and intraventricular conduction.

Anesthesia↗

Appendectomy during pregnancy: a Swedish registry study of 778 cases.

Data from three Swedish health care registries--the Medical Birth Registry, the Registry of Congenital Malformations, and the Hospital Discharge Registry--were linked for the 9-year period 1973-1981 to identify women who had appendectomy during pregnancy and their offspring, and to determine several pregnancy outcomes (gestational duration, birth weight, perinatal mortality, and congenital anomalies). Among the 720,000 deliveries during this period, 778 were complicated by appendectomy (one in 936), and the diagnosis of appendicitis was confirmed in 64% of the cases (one in 1440). Significant findings included: 1) an increase in the risk of delivery the week after appendectomy when the operation was performed after 23 weeks' gestation, with no further increase if the pregnancy continued beyond 1 week; 2) a decrease in mean birth weight of 78 +/- 24 g with more infants than expected weighing less than 3000 g; 3) an increase in the number of live-born infants dying within 7 days of birth; 4) no increase in the number of stillborn infants; and 5) no increase in the number of congenitally malformed infants.

Adult↗

Nitrous oxide alters body laterality in rats.

Seventy timed-pregnant Sprague-Dawley rats were exposed to either air (control) or 75% nitrous oxide (N2O) for 24 hours on day 8 of gestation. Four rats from each group were killed on days 11-16, 18, and 20, and laparotomy was performed. The viability of the embryos/fetuses was determined, as was the side of tail flexion on days 11 and 12, the direction from which the umbilical artery emerged from the body on days 13 and 14, the side of the body facing the placenta on days 15 and 16, and the side to which the aortic arch curved on days 18 and 20. Mean mortality rate in the control group was 8.9 +/- 6.1% (+/- S.D.), and there were no control embryos/fetuses with altered laterality except the 9% that faced left on day 16. In contrast, N2O treatment on day 8 of gestation resulted in significantly increased mortality (40.8 +/- 3.3%) beginning on day 14 of gestation and increased incidence of altered laterality overall (31.3%) and at all stages of development. The mechanisms underlying these events remain to be defined, as do the implications of our findings for pregnant surgical patients and occupationally exposed workers.

Animals↗

Neural tube defects and first trimester operations.

Swedish health care registries were used to identify women who had surgery during pregnancy and their offspring. Among the 2,252 infants born to women who had first trimester operations during 1973-1981, six had definite diagnoses of neural tube defects (expected number, 2.5). Scrutiny of the records showed that 572 operations occurred during gestational weeks 4-5, the period of neural tube formation, and that the mothers of five of the six infants with neural tube defects had an operation during that period (expected number of neural tube defects, 0.6) although one of the offspring probably had Meckel's syndrome. The relationship between neural tube defects and operation during pregnancy is discussed including the possibility that the association may be random.

Abnormalities, Drug-Induced↗

Susceptible period of nitrous oxide teratogenicity in Sprague-Dawley rats.

The susceptible period of nitrous oxide (N2O) teratogenicity was studied in 170 Sprague-Dawley rats. Seven groups of 20 timed-pregnant rats were exposed to 60% N2O for 24 hours on each of days 6-12 of gestation; a control group of 30 timed-pregnant rats was exposed to air on day 9. On day 20 of gestation, dams were killed and reproductive indices were determined; their fetuses were subsequently examined for external, skeletal, and visceral abnormalities. There were no differences among the groups in the number of implantations and live fetuses, mean fetal weight, and sex ratio. The incidence of fetal wastage was higher than control in N2O-treated groups exposed on days 8 and 11 of gestation. Skeletal malformations of the ribs and vertebrae were increased following exposure on day 9 of gestation. However, the specific minor anomaly, cervical rib, was increased only following exposure on day 8 of gestation. The incidences of right-sided aortic arch and left-sided umbilical artery, abnormalities indicative of altered laterality, were increased following exposure on day 8 of gestation. Nitrous oxide administration during organogenesis causes several reproductive defects by mechanisms which remain to be determined.

Abnormalities, Drug-Induced↗

Reproductive outcome after anesthesia and operation during pregnancy: a registry study of 5405 cases.

To define the risk of adverse reproductive outcomes after nonobstetric operations during pregnancy, we linked data from three Swedish health care registries, the Medical Birth Registry, the Registry of Congenital Malformations, and the Hospital Discharge Registry, for the years 1973 to 1981. Adverse outcomes examined were the incidences of (1) congenital anomalies, (2) stillborn infants, (3) infants dead at 168 hours, and (4) infants with very low and low birth weights. There were 5405 operations in the population of 720,000 pregnant women (operation rate, 0.75%). The incidences of congenital malformations and stillbirths were not increased in the offspring of women having an operation. However, the incidences of very-low- and low-birth-weight-infants were increased; these were the result of both prematurity and intrauterine growth retardation. The incidence of infants born alive but dying within 168 hours also was increased. No specific types of anesthesia or operation were associated with increased incidences of adverse reproductive outcomes. The cause of these outcomes was not determined.

Anesthesia↗