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1.
Clin Transl Sci ; 2(6): 405-12, 2009 Dec.
Article in English | MEDLINE | ID: mdl-20443932

ABSTRACT

A method to maintain organ blood flow during laparoscopic surgery has not been developed. Here we determined if ethyl nitrite, an S-nitrosylating agent that would maintain nitric oxide bioactivity (the major regulator of tissue perfusion), might be an effective intervention to preserve physiologic status during prolonged pneumoperitoneum. The study was conducted on appropriately anesthetized adult swine; the period of pneumoperitoneum was 240 minutes. Cohorts consisted of an anesthesia control group and groups insufflated with CO2 alone or CO2 containing fixed amounts of ethyl nitrite (1-300 ppm). Insufflation with CO2 alone produced declines in splanchnic organ blood flows and it reduced circulating levels of S-nitrosohemoglobin (i.e., nitric oxide bioactivity); these reductions were obviated by ethyl nitrite. In a specific example, preservation of kidney blood flow with ethyl nitrite kept serum creatinine and blood urea nitrogen concentrations constant whereas in the CO2 alone group both increased as kidney blood flow declined. The data indicate ethyl nitrite can effectively attenuate insufflation-induced decreases in organ blood flow and nitric oxide bioactivity leading to reductions in markers of acute tissue injury. This simple intervention provides a method for controlling a major source of laparoscopic-related morbidity and mortality: tissue ischemia and altered postoperative organ function.


Subject(s)
Hemoglobins/metabolism , Insufflation/methods , Nitric Oxide/analogs & derivatives , Nitrites/pharmacology , Pneumoperitoneum/physiopathology , Animals , Blood Gas Analysis , Carbon Dioxide , Creatinine/blood , Female , Hemodynamics/drug effects , Hydrogen-Ion Concentration/drug effects , Kidney/blood supply , Kidney/drug effects , Male , Oxygen/metabolism , Pneumoperitoneum/blood , Renal Circulation/drug effects , Splanchnic Circulation/drug effects , Sus scrofa , Time Factors
2.
Anesth Analg ; 104(2): 397-406, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17242098

ABSTRACT

BACKGROUND: The second trimester is recommended as the optimal time to conduct a surgical procedure on pregnant patients, even though the fetal responses to anesthesia at this age are not known. Here we assessed the responses of preterm fetal sheep to a standard anesthetic regimen of midazolam, thiopental, and isoflurane. METHODS: Variables were monitored in previously instrumented preterm pregnant sheep before, during, and after 4 h of general anesthesia. Isoflurane produced moderate fetal hypotension and bradycardia, whereas extubation was accompanied by increases in fetal heart rate and mean arterial blood pressure. RESULTS: We observed an initial increase in fetal Sao2 followed by a gradual decline to baseline. Within the fetal brain, oxygenated hemoglobin changed by <10% (nonsignificant) and deoxygenated hemoglobin and total hemoglobin varied by <5%. Overall, although O2 levels within the preterm fetal brain were not independently enhanced by isoflurane (as occurs in the older fetus and in the adult), they did remain constant even as fetal mean arterial pressure decreased by more than 20%. By extension, we failed to identify changes in cerebral oxygenation that could be construed as injurious. CONCLUSION: Any adverse preterm fetal response to maternal surgery should not be attributed solely to the actions of general anesthesia upon the fetus.


Subject(s)
Anesthesia, General , Fetus/drug effects , Fetus/physiology , Maternal-Fetal Exchange/drug effects , Maternal-Fetal Exchange/physiology , Anesthesia, General/adverse effects , Anesthesia, General/methods , Animals , Blood Gas Analysis , Female , Isoflurane/administration & dosage , Isoflurane/adverse effects , Pregnancy , Sheep
3.
J Cereb Blood Flow Metab ; 25(8): 1060-9, 2005 Aug.
Article in English | MEDLINE | ID: mdl-15758947

ABSTRACT

Anesthetic exposure during pregnancy is viewed as a relatively routine medical practice. However, recent rodent studies have suggested that common anesthetic agents can damage the developing brain. Here we assessed this claim in a higher order species by exposing previously instrumented near-term pregnant sheep at gestational day 122 (+/-1) to a combination of midazolam, sodium thiopental, and isoflurane at clinically relevant doses and means of anesthetic delivery (i.e., active ventilation). Four hours of maternal general anesthesia produced an initial increase in fetal systemic oxygenation and a sustained increase in fetal cerebral oxygenation, as determined by in utero near-infrared spectroscopy. Postexposure monitoring failed to identify changes in physiologic status that could be injurious to the fetal brain. Finally, through the histologic assessment of noninstrumented sheep at the same gestational time point, we found no evidence for a direct fetal neuro-toxic effect of our triple-drug regimen. Collectively, these results appear to corroborate the presumed safety of inhalational anesthetic use during pregnancy.


Subject(s)
Anesthesia, General , Anesthesia, Obstetrical , Anesthetics, Inhalation , Anesthetics, Intravenous , Brain Chemistry/drug effects , Isoflurane , Midazolam , Neurons/pathology , Oxygen Consumption/drug effects , Thiopental , Anesthesia, General/adverse effects , Anesthetics, Inhalation/adverse effects , Anesthetics, Intravenous/adverse effects , Animals , Blood Gas Analysis , Brain/embryology , Brain/pathology , Female , Fetus/physiology , Hemodynamics/drug effects , Hemoglobins/metabolism , In Situ Nick-End Labeling , Isoflurane/adverse effects , Midazolam/adverse effects , Neurons/drug effects , Pregnancy , Sheep , Thiopental/adverse effects
4.
Anesthesiology ; 101(6): 1332-8, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15564940

ABSTRACT

BACKGROUND: Anecdotal reports suggest that the second trimester is the safest time to conduct a laparoscopic procedure on a pregnant patient, but this supposition has not been tested empirically. METHODS: Previously instrumented preterm sheep (total n = 8) at gestational day 90 (term, 145 days) were anesthetized and then insufflated with carbon dioxide for 60 min at a pressure of 15 mmHg. Cardiovascular parameters were continuously recorded while blood gas status was determined before and at 15-min intervals during and up to 2 h after insufflation. RESULTS: Insufflation produced minimal maternal blood gas or cardiovascular changes except for a significant reduction in uterine blood flow. The decrease in perfusion increased fetal arterial blood partial pressure of carbon dioxide and decreased fetal pH, oxygen saturation, and oxygen content; there was also progressive fetal hypotension and bradycardia. After manually deflating the ewe, uterine blood flow returned to normal, and the fetal partial pressure of carbon dioxide and pH changes resolved within 1 h. However, fetal oxygen saturation and content remained depressed, and fetal cardiovascular status continued to decline during the 2-h postinsufflation monitoring period. CONCLUSION: Previous studies with near-term sheep determined that carbon dioxide pneumoperitoneum produces respiratory acidosis but does not decrease fetal oxygenation. In contrast, the current findings indicate that in the preterm fetus, insufflation-induced hypercapnia and acidosis are accompanied by prolonged fetal hypoxia and cardiovascular depression. This result suggests that additional work should be conducted to confirm the presumed safety of conducting minimally invasive procedures during the second trimester.


Subject(s)
Acidosis/chemically induced , Carbon Dioxide , Fetal Diseases/chemically induced , Fetal Hypoxia/chemically induced , Hypercapnia/chemically induced , Insufflation , Animals , Blood Gas Analysis , Blood Pressure/drug effects , Carbon Dioxide/metabolism , Female , Heart Rate, Fetal/drug effects , Hemodynamics/physiology , Hydrogen-Ion Concentration , Oxygen/blood , Pneumoperitoneum/chemically induced , Pneumoperitoneum/physiopathology , Pregnancy , Regional Blood Flow/drug effects , Sheep , Uterus/blood supply
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