RESUMEN
The relationship between exposure to trace concentrations of waste anesthetic gases in the operating room and the possible development of adverse health effects has concerned health care professionals for numerous years. Results of studies have been conflicting. In the late 1960s and early 1970s, some US and European epidemiological studies of operating room personnel showed an increase in the incidence of adverse health effects, including spontaneous abortion and development of congenital abnormalities in offspring. However, subsequent analysis of these studies by 2 independent groups showed that the apparent increase in adverse health effects was most likely due to flaws in these studies' methods and data collection. A later prospective study showed no causal relationship between exposure to trace concentrations of waste anesthetic gases and adverse health effects. Each institution should have a waste anesthetic gas management program that includes scavenging of waste anesthetic gases, work practices to reduce contamination, documented maintenance and regular checking of all equipment, and education of all personnel on this subject. A mechanism for reporting work-related health problems should be in place in each institution.
Asunto(s)
Anomalías Múltiples/inducido químicamente , Aborto Espontáneo/inducido químicamente , Anestésicos por Inhalación/efectos adversos , Carcinógenos/efectos adversos , Mutágenos/efectos adversos , Exposición Profesional/efectos adversos , Anomalías Múltiples/epidemiología , Aborto Espontáneo/epidemiología , Animales , Recolección de Datos , Femenino , Guías como Asunto , Humanos , Incidencia , Embarazo , Proyectos de Investigación , Sesgo de Selección , Estados Unidos/epidemiologíaRESUMEN
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.
Asunto(s)
Contaminantes Ocupacionales del Aire/análisis , Anestésicos por Inhalación/análisis , Unidades Hospitalarias , Óxido Nitroso/análisis , Enfermería Posanestésica , Periodo de Recuperación de la Anestesia , HumanosRESUMEN
Recent case reports of cauda equina syndrome after continuous spinal anesthesia have led to a reevaluation of the indications and applications of this regional anesthetic technique. However, few large studies have formally investigated the frequency of neurologic complications using macro- and microcatheter (smaller than 24 gauge) techniques. This retrospective review examines 603 continuous spinal anesthetics, including 127 administered through a 28-gauge microcatheter, performed between June 1987 and May 1992. The surgical procedure was orthopedic in 397 of 476 (83.4%) macrocatheter patients. All microcatheter patients were parturients. Three patients reported pain (persistent paresthesia) postoperatively. In two patients, the symptoms resolved in 4 days; the other patient was discharged 8 days postoperatively with residual foot pain. There was also one patient with aseptic meningitis and one patient with a sensory cauda equina syndrome (still present after 15 mo). There were 58 (9.6%) patients with a postdural puncture headache (PDPH), including 42 of 127 (33.1%) patients in the microcatheter group. An epidural blood patch was performed in 41 (6.8%) patients. The frequency of neurologic complications, excluding PDPH, is similar to those in published reviews. However, PDPH in microcatheter patients is more frequent than previously reported.
Asunto(s)
Anestesia Raquidea/efectos adversos , Cateterismo/instrumentación , Enfermedades del Sistema Nervioso/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversos , Anestesia Raquidea/instrumentación , Anestesia Raquidea/métodos , Anestésicos Locales/administración & dosificación , Anestésicos Locales/efectos adversos , Cateterismo/efectos adversos , Cateterismo/métodos , Cauda Equina , Femenino , Cefalea/etiología , Humanos , Masculino , Meningitis Aséptica/etiología , Persona de Mediana Edad , Síndromes de Compresión Nerviosa/etiología , Enfermedades del Sistema Nervioso/inducido químicamente , Parestesia/etiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Serious neurologic complications rarely occur after spinal anesthesia. Historically, the reported frequency of persistent sensory or motor deficits has ranged from 0.005% to 0.7%. However, the introduction of small-gauge needles and new local anesthetics and intrathecal adjuvants makes it necessary to reevaluate the frequency of neurologic complications after spinal anesthesia. This study is a retrospective review of 4767 consecutive spinal anesthetics performed between June 1987 and June 1990. Mean patients age was 65 +/- 15 yrs. There were 3560 (74.7%) men and 1207 (25.3%) women. A preexisting neurologic condition was present in 481 (10.1%) cases. The surgical procedures were genitourinary and lower extremity orthopedic in 4348 (91.2%) cases. A paresthesia was elicited during needle placement in 298 (6.3%) cases. Six patients reported pain upon resolution of the spinal anesthetic (persistent paresthesia). Four persistent paresthesias resolved within 1 wk; the remaining two resolved in 18-24 mo. The presence of a paresthesia during needle placement significantly increased the risk of persistent paresthesia (P < 0.001). There, were also two infectious complications. One patient with recent (treated) urosepsis underwent a urologic procedure under spinal anesthesia and subsequently developed a disc space infection. The second patient developed a paraspinal abscess. Both were treated with surgical drainage and antibiotics and remained neurologically intact. There were 62 (1.3%) patients with a postdural puncture headache, including 23 (0.5%) who underwent an epidural blood patch. These results are similar to those of previously published reviews and demonstrate the continued safety of spinal anesthesia.
Asunto(s)
Anestesia Raquidea/efectos adversos , Enfermedades del Sistema Nervioso Central/etiología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
The amount of cholesterol that circulates in the plasma as lipoproteins can be affected by the balance of cholesterol metabolism within and between the intestines and liver. In the present report, we describe a novel hypocholesterolemic agent and document its pharmacological effects in animal models of hypercholesterolemia. The oral administration of (3R,4S)-1,4-bis-(4-methoxyphenyl)-3-(3-phenylpropyl)-2-azetidinone (SCH 48461) reduced plasma cholesterol concentrations in cholesterol-fed hamsters, rats and rhesus monkeys with ED50s of 1, 2 and 0.2 mg/kg per day, respectively, SCH 48461 was also highly effective in reducing hepatic cholesteryl ester accumulation in cholesterol-fed hamsters and rats after 7 days of treatment. In one 3 week study, rhesus monkeys were fed a 0.25% cholesterol/22% saturated fat diet with or without SCH 48461. At the end of the 3 week period the control group's VLDL + LDL-cholesterol increased to 180 Mg/dl from a baseline of approximately 65 mg/dl while plasma apolipoprotein B levels had doubled. Animals treated daily with 1 mg/kg SCH 48461 maintained their baseline levels of VLDL + LDL-cholesterol, HDL-cholesterol, and plasma apolipoproteins B and A-I. After 3 weeks the diets of the two groups were switched. Within 1 week SCH 48461 (1 mg/kg per day) rapidly reversed the elevated VLDL + LDL-cholesterol levels of the previous control group to near baseline values. SCH 48461 exerted its hypocholesterolemic effect through the inhibition of cholesterol absorption. A dose of 10 mg/kg per day inhibited cholesterol absorption in cholesterol-fed hamsters by 68% while a similar reduction was achieved in chow-fed monkeys with 3 mg/kg per day. This latter dose inhibited cholesterol absorption in cholesterol-fed monkeys by 95%. Treatment of cholesterol-fed monkeys with 10 mg/kg per day SCH 48461 significantly increased fecal neutral sterol excretion (52 vs. 32 mg/kg) but had no effect on acidic sterol excretion. Using a 2-h absorption model in cholesterol-fed hamsters, SCH 48461 caused a 46% inhibition of unesterified [14C]cholesterol accumulation in the intestinal wall and a 90% inhibition of cholesteryl ester formation at a dose of 10 mg/kg. Similar data were observed when the plasma radioactivity was assessed, indicating inhibition of both free (61%) and esterified (85%) cholesterol appearance. In contrast, CI-976, a potent acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, did not affect the uptake of free cholesterol into the intestines while inhibiting cholesterol esterification (98% inhibition).(ABSTRACT TRUNCATED AT 400 WORDS)
Asunto(s)
Anticolesterolemiantes/farmacología , Azetidinas/farmacología , Colesterol/metabolismo , Hipercolesterolemia/tratamiento farmacológico , Absorción Intestinal/efectos de los fármacos , Administración Oral , Animales , Anticolesterolemiantes/uso terapéutico , Apolipoproteínas/sangre , Azetidinas/administración & dosificación , Azetidinas/uso terapéutico , Línea Celular , Colesterol/sangre , Colesterol en la Dieta , Cricetinae , Heces/química , Humanos , Hipercolesterolemia/sangre , Lipoproteínas/sangre , Hígado/efectos de los fármacos , Hígado/metabolismo , Macaca mulatta , Masculino , Mesocricetus , Ratas , Esteroles/análisisRESUMEN
One thousand orthopedic procedures in 924 patients given spinal or epidural anesthesia were prospectively studied to determine the risk of hemorrhagic complications associated with regional anesthesia. A history of excessive bruising or bleeding was elicited in 115 (12%) patients. Preoperative antiplatelet medications were taken by 386 (39%) patients. Aspirin was the most frequently reported antiplatelet drug and was taken by 193 patients. Subcutaneous heparin was administered to 22 patients before surgery on the operative day. One patient of 774 tested had a preoperative platelet count less than 100,000/mm3. In addition, 26 of 171 preoperative prothrombin times and 10 of 115 preoperative activated partial thromboplastin times were longer than normal. Only 31 preoperative bleeding times were performed; five were prolonged. There were no documented spinal hematomas (major hemorrhagic complications). Blood was noted during needle or catheter placement (minor hemorrhagic complication) in 223 (22%) patients, including 73 patients with frank blood in the needle or catheter. Preoperative antiplatelet therapy did not increase the incidence of minor hemorrhagic complications. However, female gender, increased age, a history of excessive bruising/bleeding, surgery to the hip, continuous catheter anesthetic technique, large needle gauge, multiple needle passes, and moderate or difficult needle placement were all significant risk factors. The lack of correlation between antiplatelet medications and bloody needle or catheter placement (producing clinically insignificant collections of blood in the spinal canal or epidural space) is strong evidence that preoperative antiplatelet therapy is not a significant risk factor for the development of neurologic dysfunction from spinal hematoma in patients who undergo spinal or epidural anesthesia while receiving these medications.
Asunto(s)
Anestesia Epidural/efectos adversos , Anestesia Raquidea/efectos adversos , Hematoma/etiología , Ortopedia , Inhibidores de Agregación Plaquetaria/administración & dosificación , Enfermedades de la Columna Vertebral/etiología , Punción Espinal/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Hematoma/sangre , Humanos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Estudios Prospectivos , Enfermedades de la Columna Vertebral/sangreRESUMEN
Acyl CoA: cholesterol acyltransferase (ACAT) inhibitors are known to inhibit cholesterol absorption and are under investigation to reduce hypercholesterolemia. These studies examine the effect of an ACAT inhibitor 2,2-dimethyl-N-(2,4,6-trimethoxyphenyl)-dodecanamide (PD128042) on the uptake, metabolism and secretion of cholesterol by the hamster intestinal wall in a short-term model. Preliminary studies in this model indicated that the uptake of 14C-cholesterol and its subsequent esterification 2 hr postoral dosing occurs primarily in the duodenal and jejunal segments of the small intestine and most of the radiolabeled cholesterol and cholesteryl ester in the plasma was associated with chylomicrons. In both single- and multiple-dose studies, PD128042 (50 mg kg-1 day-1) did not inhibit intestinal uptake of [14C]-cholesterol but [14C]-cholesteryl ester formation was inhibited. The free [14C]-cholesterol appearing in plasma was not affected despite a large reduction in [14C]-cholesteryl ester. In contrast, cholestyramine (1 g kg-1 day-1) inhibited the uptake of the radiolabeled free cholesterol and the appearance of cholesteryl ester in the intestine and plasma. The effects of PD128042 on cholesterol and cholesteryl ester mass associated with scraped intestinal mucosa were consistent with the effects observed with the use of the radiolabeled cholesterol. In addition, PD128042 did not affect the uptake of appearance of radiolabeled triglyceride in the intestinal wall after oral gavage of 3H-trioleoylglycerol. Taken together, the data suggest that ACAT inhibition reduces cholesterol absorption by limiting cholesteryl ester incorporation into chylomicrons and has no effect on the intestinal processing of free cholesterol to be secreted into plasma.
Asunto(s)
Anilidas/farmacología , Ésteres del Colesterol/metabolismo , Colesterol/metabolismo , Intestino Delgado/metabolismo , Esterol O-Aciltransferasa/antagonistas & inhibidores , Animales , Transporte Biológico/efectos de los fármacos , Resina de Colestiramina/farmacología , Cricetinae , Absorción Intestinal/efectos de los fármacos , Hígado/metabolismo , Masculino , Mesocricetus , Triglicéridos/metabolismoRESUMEN
Orally active inhibitors of acyl CoA:cholesterol acyl transferase (ACAT), such as Lederle CL277082 (LE), are known to reduce plasma and hepatic cholesteryl ester levels, although the mechanisms are not well understood. Several groups have reported the inhibition of cholesterol absorption upon oral ACAT inhibitor administration. In this study, we used 7-day dietary and drug treatments of hamsters to examine the possible effects of LE on hepatic ACAT. ACAT assays were performed using liver homogenates in the absence and presence of a saturating level of exogenously added cholesterol. LE (100 mg/kg/day) treatment of chow or 0.5% cholesterol-fed animals caused reductions in ACAT activity without additional cholesterol as compared with non-treated animals. When a saturating level of cholesterol was added to the assays, reductions in ACAT activity upon LE treatment of chow- or cholesterol-fed animals were also observed. Treatment of cholesterol-fed animals with cholestyramine in the diet reduced ACAT activity in the absence of added cholesterol. However, ACAT activities similar to those of non-treated animals were observed at a saturating level of cholesterol. This latter effect demonstrates that inhibition of cholesterol absorption reduces cholesterol delivery to the liver but does not reduce cholesterol esterifying capacity since cholestyramine is not absorbed and has no direct effect on the liver. The decreased ACAT activity in homogenates from LE-treated animals could also be mimicked in a dose-dependent manner by the addition of exogenous LE to liver homogenates from non-treated animals. These results indicate that hepatic ACAT activity is regulated by the availability of free cholesterol, and that orally administered LE has a direct effect on hepatic ACAT activity in the liver. In addition, the data are consistent with LE activity in the liver as being responsible, in part, for the reduced hepatic and plasma cholesteryl esters in treated animals.