Richard I. Mazze

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.

Methoxyflurane nephrotoxicity. A study of dose response in man.

Dose-related abnormalities in renal function occurred in ten of 18 patients following administration of methoxyflurane (Penthrane) with the usual anesthetic adjuvants. Eight control patients anesthetized with halothane (Fluothane) showed no abnormalities in renal function. Subclinical toxicity occurred following methoxyflurane at minimum alveolar concentration (MAC) for 2.5 to 3 hours, that is 2.5 to 3 MAC hours (serum inorganic fluoride, >50 micromols/liter), while clinical toxicity was present in all patients at dosages greater than five MAC hours (serum inorganic fluoride, >90 micromols/liter). Superimposed on the dose-response relationship were other factors that probably increased nephrotoxicity. These were as follows: individual variations in metabolism of methoxyflurane; increased sensitivity to the nephrotoxic effects of inorganic fluoride; presence of enzyme induction; and interaction of methoxyflurane with other nephrotoxic drugs. The use of methoxyflurane in clinical anesthesia should be restricted to situations where it offers specific advantages and where dosages less than 2.5 MAC hours can be attained.

Methoxyflurane Metabolism and Renal Dysfunction: Clinical Correlation in Man

Serun inorganic fluoride concentration and urinary inorganic fluoride and oxalic acid excretion were found to be markedly elevated in ten patients previously shown to have methoxyflurane-induced renal dysfunction. Five patients with climically evident renal dysfunction had a mean peak serum inorganic fluoride level (190.4 ± 20.9 μ/1) significantly higher (P < 0.02) than that of those with abnormalities in laboratory tests only (105.8 ± 17.0 μ/1). Similarly, patients with clinically evident renal dysfunction had a mean peak oxalic acid excretion (286.8 ± 39.3 mg/24 hours) significantly greater (P < 0.05) than that of those with laboratory abnormalities only (130.6 ± 51.4 mg/24 hours). That patients anesthetized with halothane had insignificant changes in serum inorganic fluoride concentration and oxalic acid excretion indicates that these substances are products of methoxyflurane metabolism. A proposed metabolic pathway to support this hypothesis is presented, as well as evidence to suggest that inorganic fluoride is the substance responsible for methoxyflurane; induced renal dysfunction.

Halothane, isoflurane, and enflurane MAC in pregnant and nonpregnant female and male mice and rats.

The MAC of halothane, isoflurane, and enflurane was determined using the tail-clamp technique in pregnant female, nonpregnant female, and male Swiss Webster mice (n = 216) and Sprague-Dawley rats (n = 112). Mean MAC values (+/-SD) for halothane, isoflurane, and enflurane in mice were 0.95 +/- 0.07%, 1.34 +/- 0.10%, and 1.95 +/- 0.16%, respectively; values in rats were 1.03 +/- 0.04%, 1.46 +/- 0.06%, and 2.21 +/- 0.08%, respectively, all significantly higher than in mice. Neither the sex of the animals nor whether female animals were pregnant influenced the results.

Inorganic fluoride nephrotoxicity: prolonged enflurane and halothane anesthesia in volunteers.

The effects of prolonged enflurane and halothane administration on urine-concentrating ability were determined in volunteers by examining their responses to vasopressin before anesthesia and on days 1 and 5 after anesthesia. A significant decrease in maximum urinary osmolality of 264 +/- 34 mOsm/kg (26 per cent of the preanesthetic value) was present on day 1 after enflurane anesthesia, whereas subjects anesthetized with halothane had a significant increase in maximum urinary osmolality of 120 +/- 44 mOsm/kg. Serum inorganic fluoride level peaked at 33.6 muM and remained above 20 muM for approximately 18 hours. Thus, the threshold level for inorganic fluoride nephrotoxicity is lower than previously suspected.

ECONOMIC BENEFITS ATTRIBUTED TO OPENING A PREOPERATIVE EVALUATION CLINIC FOR OUTPATIENTS

S ince 1990, more than 50% of all hospital-based surgeries performed in the United States have been performed on an outpatient basis (1). Many of these patients have their preoperative evaluation completed by the anesthesiologist on the day of their procedure. It is unclear whether healthy adults benefit from preoperative evaluation prior to the day of surgery (2-5), but it has been demonstrated that hospital efficiency is enhanced by early preoperative evaluation (6-9). In particular, delays and cancellations are decreased when outpatients have been evaluated in a preoperative evaluation clinic prior to the day of operation (6,9).i In November 1994, our university-affiliated Department of Veterans Affairs Hospital established a perioperative unit for outpatients. This unit provides preoperative services, such as registration, preoperative evaluations, and preoperative holding, as well as postsurgical support for outpatients, including a Phase 2 recovery area. The most important single element of our program has been the interdisciplinary preoperative evaluation clinic for outpatients under the medical direction of an anesthesiologist and staffed by nursing personnel. Similar clinics have reported decreased laboratory utilization (9,10), lower surgical cancellation rates (9,11,12), and fewer and shorter hospitalizations (10,12). The magnitude of inpatient cost savings attributable to reducing hospitalization has not been fully described. The purpose of this report is to document these savings and also to document the change in the cancellation rate that resulted after our clinic opened.

Renal Effects and Metabolism of Isoflurane in Man

The intra- and postanesthetic renal effects and metabolism of isoflurane were studied in nine surgical patients; six control patients received halothane. Isoflurane was metabolized to a slight extent, with a mean peak serum inorganic fluoride concentration of 4.4 ± 0.4 µM/l, measured six hours after anesthesia. Dose-related increases of inorganic and organic fluoride were found in the urine. At comparable anesthetic exposures five to ten times more organic fluoride metabolites of halothane were detected. Postanesthetic renal function, including the response to vasopressin, was normal in both groups. Intra-anesthetic depressions of renal blood flow (51 percent of control), glomerular filtration rate (63 per cent of control) and urinary flow rate (34 per cent of control) during isoflurane anesthesia were similar to those seen with halothane. Metabolism of isoflurane to inorganic fluoride is of insufficient magnitude to cause renal dysfunction.

Metabolism and Renal Effects of Enflurane in Man

The metabolism and renal effects of enflurane were studied during and after anesthesia in ten surgical patients without renal disease; ten control patients received halothane. Enflurane was metabolized to inorganic fluoride with a mean peak serum level of 22.2 ± 2.8 µM four hours after anesthesia. Urinary inorganic and organic fluoride excretions were increased but oxalic acid excretion was not. suggesting that the latter is not an enflurane metabolite. Postanesthetic renal function, including the response to vasopressin, was normal in both groups. During enflurane anesthesia renal blood flow, glomerular filtration rate, and urinary flow rate were 77, 79, and 67 per cent of control values, respectively. In this study of patients without renal disease, metabolism of enflurane to inorganic fluoride was insufficient to cause clinically significant renal dysfunction.

Dose-related Methoxyflurane Nephrotoxicity in Rats: A Biochemical and Pathologic Correlation

Dose-related nephrotoxicity after administration of methoxyflurane was demonstrated in rats of the Fischer 344 strain. This was characterized by Pitressin-resistant polyuria, hypernatremia, serum hyperosmolality, and increased serum urea nitrogen and inorganic fluoride concentrations. Urinary sodium, potassium, osmolality, and urea nitrogen concentrations were decreased in proportion to the dose administered. Light and electron microscopic changes were most prominent in the proximal convoluted tubules and were also dose-related. Injection of inorganic fluoride produced changes in renal function and histology similar to those seen after administration of methoxyflurane. It was concluded that methoxyflurane produced dose-related nephrotoxicity due to increased concentrations of its metabolite, inorganic fluoride.

Hyperkalemia and cardiovascular collapse following administration of succinylcholine to the traumatized patient.

Mean arterial potassium increased 84 per cent in 14 massively traumatized soldiers following administration of succinylcholine, 1 mg/kg, for intubation. A control group of patients showed only an 11 per cent increase. In five traumatized patients, potassium increased from an average of 3.8 mEg/1 lo 9.5 mEg/l. Three of the five patients suffered cardiovascular collapse, with ECGs consistent with hyperkateinia. It seems advisable to defer the use of succinylcholine in massively traumatized patients until all wounds are closed, infection has cleared, and cataholism is reversed.