May 2014

Mark your calendar!

SmartTots Workshop

Friday, June 20, 2014: Crystal City Marriott at Reagan National Airport, Washington, DC

Open to all interested professionals. No registration fee.

Workshop Objectives:

  1. Develop a shared understanding of the recent and ongoing studies regarding pediatric anesthesia neurotoxicity, including rationale, study design, and results to date.
  2. Determine what additional studies are needed, including study design and cost.
  3. Identify strategies for a proposal to government sources to raise the funds required to conduct the needed studies.

Please contact Rebekah Davies, IARS Program Manager for more information or to register for the workshop.  [email protected]   415-296-6905

Research News & Updates

Comparative Analysis of Outcome Measures Used in Examining Neurodevelopmental Effects of Early Childhood Anesthesia Exposure

When assessing cognition in children with early exposure to anesthesia, the results may depend on the outcome measure used. Neuropsychological and International Classification of Diseases, 9th Revision, Clinical Modification-coded clinical outcomes showed an increased risk of deficit in exposed children compared with that in unexposed children, whereas academic achievement scores did not. This may explain some of the variation in the literature and underscores the importance of the outcome measures when interpreting studies of cognitive function.  Read more

The association between brain injury, perioperative anesthetic exposure, and 12-month neurodevelopmental outcomes after neonatal cardiac surgery: a retrospective cohort study. 

After adjustment for multiple relevant covariates, we demonstrated an association between VAA exposure, brain injury, ICU length of stay, and lower neurodevelopmental outcome scores at 12 months of age. These findings support the need for further studies to identify potential modifiable factors in the perioperative care of neonates with CHD to improve neurodevelopmental outcomes.  Read more

Anesthetic neurotoxicity

This article provides an overview of the currently available data from both animal experiments and human clinical studies regarding the effects of sedatives and anesthetics on the developing brain.  Read more

Anesthesia and the Developing Brain: Relevance to the Pediatric Cardiac Surgery

Children potentially at greater risk for anesthetic neurotoxicity, based on a prolonged anesthetic exposure early in development, are those receiving anesthesia for surgical repair of congenital heart disease. These children not only receive prolonged anesthetic exposure during surgical repair but also repeated anesthetic exposures during a critical period of brain development. Their propensity to abnormal brain development, as a result of congenital heart disease, may modify their risk of anesthetic neurotoxicity. This review article provides insight into basic science and clinical investigations as it relates to this unique group of children.  Read more

Neonatal exposure to sevoflurane causes significant suppression of hippocampal long-term potentiation in postgrowth rats.

Our present findings indicate that neonatal exposure to sevoflurane at a higher concentration can cause alterations in the hippocampal synaptic plasticity that persists into adulthood.  Read more

Anaesthetics-Induced Neurotoxicity in Developing Brain: An Update on Preclinical Evidence

The mechanisms and human applicability of anaesthetic neurotoxicity and neuroprotection have remained under intense investigation over the past decade. Ongoing pre-clinical investigation may have significant impact on clinical practice in the near future. This review represents recent developments in this rapidly emerging field. We summarize laboratory data published after 2010, in the field of anaesthetics-induced neurotoxicity and its impact on cognitive function, and we discuss findings in mechanisms of early-life anaesthetics-induced neurotoxicity, the role of human stem cell-derived models in detecting such toxicity, and new potential alleviating strategies.  Read more

Basic aspects of the potential toxicity of anesthetic drugs

During the last decade, numerous in vitro and in vivo experimental studies in newborn animal models have established the neurotoxic effects of most anesthetic and sedative drugs used in pediatrics.  These data are insufficient to change our practices, however progress in experimental research will help us identify the safest therapeutic strategies and neuroprotective treatments.   Read more

Subclinical Carbon Monoxide Limits Apoptosis in the Developing Brain After Isoflurane Exposure

It is possible that low-flow anesthesia designed to target rebreathing of specific concentrations of CO may be a desired strategy to develop in the future in an effort to prevent anesthesia-induced neurotoxicity in infants and children.  Read more

Neurotoxic effects of dexmedetomidine in fetal cynomolgus monkey brains

The underlying mechanism by which dexmedetomidine reduces neuronal injury during a prolonged anesthesia remains unclear. In this study, we compare the neurotoxic effects of dexmedetomidine and ketamine, a general anesthetic with a different mechanism of action, in fetal cynomolgus monkeys.  In utero treatment with ketamine resulted in marked apoptosis and degeneration primarily in layers I and II of the frontal cortex. In contrast, fetal brains from animals treated with dexmedetomidine showed none to minimal neuroapoptotic or neurodegenerative lesions at both low- and high-dose treatments.  Read more

Dexmedetomidine Reduces Isoflurane-Induced Neuroapoptosis Partly by Preserving P13K/Akt Pathway in the Hippocampus of Neonatal Rats

Prolonged exposure to volatile anesthetics, such as isoflurane and sevoflurane, causes neurodegeneration in the developing animal brains. Recent studies showed that dexmedetomidine, a selective α2-adrenergic agonist, reduced isoflurane-induced cognitive impairment and neuroapoptosis. The mechanisms for the effect are not completely clear.  Our results suggest that dexmedetomidine pretreatment provides neuroprotection against isoflurane-induced neuroapoptosis in the hippocampus of neonatal rats by preserving PI3K/Akt pathway activity.  Read more

Isoflurane exposure in newborn rats induces long-term cognitive dysfunction in males but not females

There is mounting evidence that children exposed to anesthetic agents sustain lasting effects on learning and memory. Rodent models have shown that isoflurane exposure in newborns induces acute neuroapoptosis and long-term cognitive impairment.  In our study on male and female Sprague Dawley rats, we found that isoflurane exposure significantly increased neuronal death in each brain region with no difference between sexes. However, only males were impaired in the recognition of objects in different locations and contexts. Males also exhibited deficient social memory while females were intact.  Read more

Exposure to general anesthesia in early life and the risk of attention deficit/hyperactivity disorder development: a nationwide, retrospective matched-cohort study

Exposure to general anesthesia before 3 years of age was not associated with ADHD.  Read more

Neuroprotective gases–fantasy or reality for clinical use?

In this review, we summarize the literature concerning the neuroprotective effect of each gas and its underlying mechanisms, extract common targets reported for the neuroprotective effects of different gases, highlight the conflicting observations from clinical trials and further discuss the possible hindrances impeding clinical applications in order to propose future research perspectives and therapeutic exploitations.  Read more

Neonatal Morphine in Extremely and Very Preterm Neonates: Its Effect on the Developing Brain, a Review

Preterm infants requiring intensive care experience procedures requiring management of stress and pain. This overview of research on the use of morphine and its neurodevelopmental effects on neonates finds no definite conclusions concerning the effects of neonatal morphine on long term neurodevelopmental outcomes. More prospectively designed trials should be conducted using reliable and validated pain assessment scores to evaluate effects of morphine on long term neurodevelopmental outcomes in preterm infants.  Read more