Supplementing desflurane with intravenous anesthesia reduces fetal cardiac dysfunction during open fetal surgery
Department of Anesthesiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. Pediatric Anesthesia
(Impact Factor: 1.85).
08/2010; 20(8):748-56. DOI: 10.1111/j.1460-9592.2010.03350.x
To lower the incidence and severity of fetal cardiovascular depression during maternal fetal surgery under general anesthesia.
We hypothesized that supplemental intravenous anesthesia (SIVA) with propofol and remifentanil would lower the need for high-dose inhalational anesthesia and provide adequate maternal depth of anesthesia and uterine relaxation. SIVA technique would minimize prolonged fetal exposure to deep inhalational anesthetics and significant intraoperative fetal cardiovascular depression.
Fetal hypoxia and significant fetal hemodynamic changes occur during open fetal surgery because of the challenges such as surgical manipulation, hysterotomy, uterine contractions, and effects of anesthetic drugs. Tocolysis, a vital component of fetal surgery, is usually achieved using volatile anesthetic agents. High concentrations of volatile agents required to provide an appropriate degree of uterine relaxation may cause maternal hypotension and placental hypoperfusion, as well as direct fetal cardiovascular depression.
We reviewed medical records of 39 patients who presented for ex utero intrapartum treatment and mid-gestation open fetal surgery between April 2004 and March 2009. Out of 39 patients, three were excluded because of the lack of echocardiographic data; 18 patients received high-concentration desflurane anesthesia and 18 patients had SIVA with desflurane for uterine relaxation. We analyzed the following data: demographics, fetal medical condition, anesthetic drugs, concentration and duration of desflurane, maternal arterial blood pressure, intraoperative fetal echocardiogram, presence of fetal bradycardia, and need for intraoperative fetal resuscitation.
Adequate uterine relaxation was achieved with about 1.5 MAC of desflurane in the SIVA group compared to about 2.5 MAC in the desflurane only anesthesia group (P = 0.0001). More fetuses in the high-dose desflurane group compared to the SIVA group developed moderate-severe left ventricular systolic dysfunction over time intraoperatively (P = 0.02). 61% of fetuses in the high-dose desflurane group received fetal resuscitative interventions compared to 26% of fetuses in the SIVA group (P = 0.0489).
SIVA as described provides adequate maternal anesthesia and uterine relaxation, and it allows for decreased use of desflurane during open fetal surgery. Decreased use of desflurane may better preserve fetal cardiac function.
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ABSTRACT: Significant advances in perinatal and neonatal medicine over the last 20 years and the recent emergence of fetal surgery has resulted in anesthesia providers caring for a growing number of infants born at the margin of viability. Anesthetic management in this patient population has to take into consideration the immature function of many vital organ systems as well as the effects of the underlying disease processes, which can frequently lead to severe physiological derangements. Accordingly, premature infants presenting for major surgeries early in life can represent a significant anesthetic challenge. However, even with advanced anesthetic and surgical management and optimal intensive care, extremely premature infants face substantial postoperative morbidity and mortality, as well as prolonged hospital courses. In this article, we will discuss the following questions: How far have we come in improving outcomes of extreme prematurity? And what will the future medical and societal challenges be, as we continue to redefine the limits of viability?
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ABSTRACT: Certain anesthetics exhibit neurotoxicity in the brains of immature but not mature animals. γ-Aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the adult brain, is excitatory on immature neurons via its action at the GABAA receptor, depolarizing the membrane potential and inducing a cytosolic Ca2+ increase ([Ca2+]i), because of a reversed transmembrane chloride gradient. Recent experimental data from several rodent studies have demonstrated that exposure to isoflurane during an initial phase causes neuronal excitotoxicity and apoptosis. GABAA receptor-mediated synaptic voltage-dependent calcium channels' (VDCCs) overactivation and Ca2+ influx are involved in these neural changes.
We monitored [Ca2+]i using Fluo-4 AM fluorescence imaging. Using whole-cell patch clamp techniques, IVDCC (voltage-dependent calcium channel currents) were recorded from primary cultures of rat hippocampal neurons (5-day culture) exposed to isoflurane. To further investigate the neurotoxicity of high cytosolic-free calcium after isoflurane in a dose- and time-dependent manner, the possibility of increased caspase-3 levels was evaluated by Western blot and quantitative real-time polymerase chain reaction. Statistical significance was assessed using the Student t test or 1-way analysis of variance followed by the Tukey post hoc test.
Under control conditions, isoflurane enhanced the GABA-induced [Ca2+]i increase in a dose-dependent manner. Dantrolene and nicardipine markedly inhibited this enhancement mediated by isoflurane. Moreover, in Ca2+-free media, pretreatment with isoflurane did not show any influence on the caffeine-induced increase of [Ca2+]i. Similarly, using whole-cell recording, isoflurane increased the peak amplitude of IVDCC in the cultured neurons from rat hippocampus by depolarization pulses. Isoflurane (0.25, 0.5, 0.75, and 1 minimum alveolar concentration [MAC]) potentiated IVDCC peak current amplitude by 109.11%±9.03%, 120.56%±11.46%, 141.33%±13.87%, and 146.78%±15.87%, respectively. To analyze variation in protein levels, the effect of treatments with isoflurane on caspase-3 activity was dose- and time-dependent, reaching a maximal caspase-3 activity after exposure to 1 MAC for 6 hours (P<0.001). However, in the mRNA levels, hippocampal caspase-3 mRNA levels began to be significantly increased in isoflurane-treated developing rat hippocampal neurons after 6 hours of exposure to 0.25 MAC isoflurane (P<0.001).
Isoflurane-mediated enhancement of GABA-triggered [Ca2+]i release results from membrane depolarization with subsequent activation of VDCCs and further Ca2+-induced Ca2+ release from the ryanodine-sensitizing Ca2+ store. An increase in [Ca2+]i, caused by activation of the GABAA receptor and opening of VDCCs, is necessary for isoflurane-induced calcium overload of immature rat hippocampal neurons, which may be involved in the mechanism of an isoflurane-induced neurotoxic effect in the developing rodent brain.
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