Singular and short-term anesthesia exposure in the developing brain induces persistent neuronal changes consistent with chronic neurodegenerative disease.

The potential adverse impact of inhalational anesthetics on the developing brain was highlighted by the addition of a medication warning by the U.S. Food and Drug Administration for their use in the pediatric population.

Effect of combining anesthetics in neonates on long-term cognitive function.

Background: With growing evidence that anesthesia exposure in infancy affects cognitive development, it is important to understand how distinct anesthetic agents and combinations can alter long-term memory. Investigations of neuronal death suggest that combining anesthetic agents increases the extent of neuronal injury. However, it is unclear how the use of simultaneously combined anesthetics affects cognitive outcome relative to the use of a single agent.

Effect of general anesthesia in infancy on long-term recognition memory in humans and rats.

Anesthesia in infancy impairs performance in recognition memory tasks in mammalian animals, but it is unknown if this occurs in humans. Successful recognition can be based on stimulus familiarity or recollection of event details. Several brain structures involved in recollection are affected by anesthesia-induced neurodegeneration in animals.

Biphasic change of progenitor proliferation in dentate gyrus after single dose of isoflurane in young adult rats.

Background: Isoflurane exposure causes improvement in long-term neurocognitive function in young adult rats; this is associated with an increase in dentate gyrus (DG) progenitor proliferation 4 days after anesthesia. However, the number of new neurons that were born from cells that incorporated bromodeoxyuridine (BrdU) 4 days after anesthesia is not affected by anesthesia. We tested the hypothesis that progenitor proliferation continues to increase past 4 days, which would imply the possibility that the number of new neurons after anesthesia could be increased if BrdU labeling occurred at a later time point.

Propofol at clinically relevant concentrations increases neuronal differentiation but is not toxic to hippocampal neural precursor cells in vitro.

Background: Propofol in the early postnatal period has been shown to cause brain cell death. One proposed mechanism for cognitive dysfunction after anesthesia is alteration of neural stem cell function and neurogenesis. We examined the effect of propofol on neural precursor or stem cells (NPCs) grown in vitro.

Delayed environmental enrichment reverses sevoflurane-induced memory impairment in rats.

Background: Anesthesia given to immature rodents causes cognitive decline, raising the possibility that the same might be true for millions of children undergoing surgical procedures under general anesthesia each year. We tested the hypothesis that anesthesia-induced cognitive decline in rats is treatable. We also tested if anesthesia-induced cognitive decline is aggravated by tissue injury.

Review article: Neurotoxicity of anesthetic drugs in the developing brain.

Anesthesia kills neurons in the brain of infantile animals, including primates, and causes permanent and progressive neurocognitive decline. The anesthesia community and regulatory authorities alike are concerned that is also true in humans. In this review, I summarize what we currently know about the risks of pediatric anesthesia to long-term cognitive function.

Beyond anesthetic properties: the effects of isoflurane on brain cell death, neurogenesis, and long-term neurocognitive function.

Anesthetic drugs cause brain cell death and long-term neurocognitive dysfunction in neonatal rats. Recently, human data also suggest that anesthesia early in life may cause cognitive impairment. The connection between cell death and neurocognitive decline is uncertain.

Isoflurane does not affect brain cell death, hippocampal neurogenesis, or long-term neurocognitive outcome in aged rats.

Background: Roughly, 10% of elderly patients develop postoperative cognitive dysfunction. General anesthesia impairs spatial memory in aged rats, but the mechanism is not known. Hippocampal neurogenesis affects spatial learning and memory in rats, and isoflurane affects neurogenesis in neonatal and young adult rats.

Beyond anesthetic properties: the effects of isoflurane on brain cell death, neurogenesis, and long-term neurocognitive function.

Anesthetic drugs cause brain cell death and long-term neurocognitive dysfunction in neonatal rats. Recently, human data also suggest that anesthesia early in life may cause cognitive impairment. The connection between cell death and neurocognitive decline is uncertain.

Increasing the duration of isoflurane anesthesia decreases the minimum alveolar anesthetic concentration in 7-day-old but not in 60-day-old rats.

Background: While studying neurotoxicity in rats, we observed that the anesthetic minimum alveolar anesthetic concentration (MAC) of isoflurane decreases with increasing duration of anesthesia in 7-day-old but not in 60-day-old rats. After 15 min of anesthesia in 7-day-old rats, MAC was 3.5% compared with 1.

Isoflurane differentially affects neurogenesis and long-term neurocognitive function in 60-day-old and 7-day-old rats.

Background: Anesthetic agents cause cell death in the developing rodent brain and long-term, mostly hippocampal-dependent, neurocognitive dysfunction. However, a causal link between these findings has not been shown. Postnatal hippocampal neurogenesis affects hippocampal function into adulthood; therefore, the authors tested the hypothesis that isoflurane affects long-term neurocognitive function via an effect on dentate gyrus neurogenesis.

Isoflurane inhibits growth but does not cause cell death in hippocampal neural precursor cells grown in culture.

Background: Isoflurane causes long-term hippocampal-dependent learning deficits in rats despite limited isoflurane-induced hippocampal cell death, raising questions about the causality between isoflurane-induced cell death and isoflurane-induced cognitive function. Neurogenesis in the dentate gyrus is required for hippocampal-dependent learning and thus constitutes a potential alternative mechanism by which cognition can be altered after neonatal anesthesia. The authors tested the hypothesis that isoflurane alters proliferation and differentiation of hippocampal neural progenitor cells.

Effect of hypercarbia and isoflurane on brain cell death and neurocognitive dysfunction in 7-day-old rats.

Background: Millions of neonates undergo anesthesia each year. Certain anesthetic agents cause brain cell death and long-term neurocognitive dysfunction in postnatal day (P)7 rats. Despite its intuitive appeal, a causal link between cell death and neurocognitive decline after anesthesia has not been established.

Epidural blood patch for headache after lumboperitoneal shunt placement.

Headaches complicating lumboperitoneal (LP) shunt placement have been attributed to shunt failure with resultant high intracranial pressure or to overdrainage with resultant low intracranial pressure. In this case, a 17-yr-old girl had symptoms of a low-pressure headache after LP shunt placement alleviated by an epidural blood patch. The success of this therapy suggests postdural puncture as a possible cause for low-pressure headache after LP shunt placement.

Reversal of direct thrombin inhibition after cardiopulmonary bypass in a patient with heparin-induced thrombocytopenia.

Unlabelled: We treated persistent hemorrhage after cardiopulmonary bypass in a heart transplant recipient who had received anticoagulation with the direct thrombin inhibitor bivalirudin by a combination therapy aimed at reducing the plasma concentration of the thrombin antagonist (hemodialysis and modified ultrafiltration), increasing the concentration of thrombin at bleeding sites (recombinant factor VIIa), and increasing the plasma concentration of other coagulation factors (fresh frozen plasma and cryoprecipitate). The bleeding was controlled, and there was no thrombotic complication.

Implications: A combination of modified ultrafiltration, hemodialysis, and the administration of recombinant factor VIIa, fresh frozen plasma, and cryoprecipitate may reverse the anticoagulant effect of bivalirudin.

Deep hypothermic circulatory arrest and the femoral-to-radial arterial pressure gradient.

Objectives: To determine the femoral-to-radial arterial pressure gradient, as well as the factors associated with them, in patients receiving cardiopulmonary bypass (CPB) with profound hypothermia and circulatory arrest.

Design: Retrospective automated hemodynamic record review.

Setting: University hospital.

Profound hypoxemia resulting from shunting across an inadvertent atrial septal tear after left ventricular assist device placement.

Unlabelled: Defects within the interatrial septum (IAS) can be a source of significant right-to-left shunting and hypoxemia, particularly after placement of a left ventricular assist device (LVAD). We report a case of LVAD placement in which an unrecognized IAS tear occurred intraoperatively, leading to profound arterial desaturation. Transesophageal echocardiography (TEE) was instrumental in making the diagnosis.

Use of recombinant factor VIIa as a rescue treatment for intractable bleeding following repeat aortic arch repair.

Hemorrhage, refractory to aggressive conventional therapy, at a rate of 16 L/hr following separation from cardiopulmonary bypass for aortic arch repair, was controlled with a dose of 90 microg/kg of recombinant factor VIIa, repeated once after 2 hours.

gamma-Aminobutyric acid-A receptors contribute to isoflurane neuroprotection in organotypic hippocampal cultures.

Unlabelled: The mechanisms by which anesthetics such as isoflurane reduce cell death in rodent models of cerebral ischemia remain incompletely defined. Reduction in glutamate excitotoxicity explains some but not all of isoflurane's neuroprotection. Because isoflurane potentiates gamma-aminobutyric acid (GABA) receptor-mediated ion fluxes and GABA(A) receptor agonists have neuroprotective effects, we hypothesized that GABA(A) receptors contribute to isoflurane neuroprotection.