Anesthesia and Developing Brain

Shridevi Pandya Shah* and Ornella Lemonius

Department Anesthesiology, Rutgers-NJMS, USA

*Corresponding author: Shridevi Pandya Shah, Department Anesthesiology, Rutgers-NJMS, USA

Received: August 08, 2014; Accepted: August 10, 2014; Published: August 11, 2014

The advent of pediatric anesthesia in the mid-1800s was the era of increased surgical intervention in the pediatric population. The first documented case of anesthesia in a child was the administration of ether by Dr. Crawford Long on an 8-year-old child for toe amputation in 1842. As the field of pediatric surgery evolved, pediatric anesthesia followed suite and currently approximately 450,000 pediatric surgeries are performed annually in the United States. Of these, approximately 25% are in children under the age of 3 years [1].

Presently used anesthetics act by two principal mechanisms; either by increased inhibition via GABA receptors or by decreasing excitation through NMDA receptors. In pediatric and obstetrical medicine it is common practice to utilize anesthetic agents that act by either of these mechanisms. Consequently, when evidence based medicine confirmed that anesthesia had neurotoxic effects in the brain of infantile animals, including primates and caused progressive, permanent neurocognitive decline; it became prudent for regulatory authorities and anesthesiologists to be concerned.

In late 1990s the neuroapoptotic effects of agents that agonize the GABA receptors and antagonize excitatory NMDA receptors was described by Franks and Leib (1994) and Jevtovic-Todoric et al. (1998) respectively [2]. Later, in 2003, a study performed on seven day old Sprague Dawley rats using combination anesthesia (nitrous oxide, isoflurane, midazolam) showed significant neurodegeneration in the laterodorsal, anteventral thalamic nuclei and parietal cortex and suppression of long term potentiation in the hippocampus resulting in loss of memory and spatial learning [3].

In 2011, Paule et al. published a study on the effect of ketamine in neonatal rhesus monkeys which showed cognitive delay at a later age. Additionally, long term impairment of cognitive function in monkeys exposed to ketamine in utero at gestational age 120-123 days was confirmed at age 1.5 and 3 years [4].

Multiple studies performed on rats at our institution by Dr. Xiong and his team supports the current evidence. His study showed significant reduction of the neuron population in the CA 1 and CA 3 regions of the hippocampus at postnatal age 10 and 28 days following exposure to propofol in utero [5]. Additionally, there was substantial reduction in synaptiphysin expression in the hippocampus of postnatal age 28 days as well as memory impairment [6].

Despite numerous studies documenting the neuroapoptotic effects of certain anesthetic agents; other studies have shown some agents to have neuroprotective effects.

In 2012, Ponte et al. showed that administration of clonidine eliminated the adverse effects of ketamine in the mouse model [7]. The protective effects of clonidine on ketamine induced apoptosis and behavioral changes were demonstrated. Moreover, when used alone, clonidine was shown to have no negative effects on apoptosis or behavior. However, further studies are needed to elucidate the mechanism of clonidine associated neuro-protection and to determine whether or not these beneficial properties are evident in other anesthetics.

Other agents shown to have neuroprotective properties include melatonin and lithium. Melatonin partially inhibits apoptotic pathways and decreases activation of caspase-3 [8]. Lithium prevents the suppression of ketamine induced and propofol induced ERK phosphorylation, thereby reducing apoptosis [9].

The role of newer agents such as caspase inhibitors, antiinflammatories, growth factors (erythropoietin, stem cells), antioxidants (melatonin, allopurinol) and xenon modulation of NMDA - 2^nd messenger system are currently under investigation. Although promising, further studies need to be performed to document their effectiveness on neuroprotection [10].

There has been extensive literature on protective effects of hypothermia in varieties of settings in adults as well as children and preterm babies. In 2012, Tagin et al, showed reduction in the risk of death or major neurodevelopmental disability at age 18 months in newborns with moderate hypoxic ischemic encephalopathy [11].

Almost half million babies are born prematurely (less than 37 weeks of gestation) each year in the United States. Preterm infants are subject to hospitalization and surgery is often required to sustain life [12]. Given the current research findings, the Federal Drug Agency (FDA) has provided preliminary recommendations stating that if possible, anesthesia should be postponed until the child is at least 6 months of age. Consequently, there exists a need for ongoing research to further elucidate safer anesthetic agents and techniques.

Anesthesia and Developing Brain

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