Ketamine potentiates cerebrocortical damage induced by the common anaesthetic agent nitrous oxide in adult rats

Jevtović-Todorović, Vesna; Benshoff, N.; Olney, John W.

doi:10.1038/sj.bjp.0703479

Cited by 84 publications

(77 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When these drugs, including virtually all anesthetics, are administered to young animals (including primates), neurodegeneration results. 2,4,5,7,9,10 Few studies provide insight into the potential clinical significance of these observations. [11][12][13] Recently, we reported an association between multiple, but not single, exposures to anesthesia/surgery before the age of 4 and subsequent learning disabilities (LDs).…”

mentioning

confidence: 99%

Cognitive and Behavioral Outcomes After Early Exposure to Anesthesia and Surgery

Flick¹,

Katusic²,

Colligan³

et al. 2011

Pediatrics

838

548

View full text Add to dashboard Cite

WHAT'S KNOWN ON THIS SUBJECT:Exposure to virtually all anesthetic drugs has been shown to cause neurodegeneration in young animals. Studies of learning and cognition in children exposed to anesthesia and surgery have been few, have relied on single outcome measures, and have not controlled for comorbidity. WHAT THIS STUDY ADDS:In this study of children exposed to anesthesia/surgery before the age of 2, multiple group and individual measures of learning and behavior are examined by using a matched design with adjustment for comorbidity using 2 separate methods. abstract + BACKGROUND: Annually, millions of children are exposed to anesthetic agents that cause apoptotic neurodegeneration in immature animals. To explore the possible significance of these findings in children, we investigated the association between exposure to anesthesia and subsequent (1) learning disabilities (LDs), (2) receipt of an individualized education program for an emotional/behavior disorder (IEP-EBD), and (3) scores of group-administered achievement tests. METHODS:This was a matched cohort study in which children (N ϭ 8548) born between January 1, 1976, and December 31, 1982, in Rochester, Minnesota, were the source of cases and controls. Those exposed to anesthesia (n ϭ 350) before the age of 2 were matched to unexposed controls (n ϭ 700) on the basis of known risk factors for LDs. Multivariable analysis adjusted for the burden of illness, and outcomes including LDs, receipt of an IEP-EBD, and the results of groupadministered tests of cognition and achievement were outcomes. RESULTS:Exposure to multiple, but not single, anesthetic/surgery significantly increased the risk of developing LDs (hazard ratio: 2.12 [95% confidence interval: 1.26 -3.54]), even when accounting for health status. A similar pattern was observed for decrements in groupadministered tests of achievement and cognition. However, exposure did not affect the rate of children receiving an individualized education program. CONCLUSIONS:Repeated exposure to anesthesia and surgery before the age of 2 was a significant independent risk factor for the later development of LDs but not the need for educational interventions related to emotion/behavior. We cannot exclude the possibility that multiple exposures to anesthesia/surgery at an early age may adversely affect human neurodevelopment with lasting consequence.

show abstract

mentioning

confidence: 99%

Cognitive and Behavioral Outcomes After Early Exposure to Anesthesia and Surgery

Flick¹,

Katusic²,

Colligan³

et al. 2011

Pediatrics

838

548

View full text Add to dashboard Cite

show abstract

“…To administer a specific concentration of N 2 O/oxygen and isoflurane in a highlycontrolled environment, the anesthesia chamber was used [8,9,11]. Animals were kept normothermic throughout the experiment, as previously described [12]. For control experiments, air was substituted for the gas mixtures.…”

Section: Methodsmentioning

confidence: 99%

General anesthesia activates BDNF-dependent neuroapoptosis in the developing rat brain

et al. 2006

Self Cite

View full text Add to dashboard Cite

Brain-derived neurotrophic factor (BDNF) is important in supporting neuronal development. BDNF imbalance due to excessive neuronal inhibition can result in the apoptotic degeneration of developing neurons. Since general anesthetics cause profound depression of neuronal activity and are known to induce widespread degeneration in the developing brain, we studied their potential to activate BDNF-mediated developmental neuroapoptosis. When P7 rats (at the peak of brain development) were exposed to a commonly-used and highly pro-apoptotic anesthesia protocol (midazolam, isoflurane, nitrous oxide) for a period of 2, 4 or 6 h, we found that anesthesia modulates the key steps in BDNF-activated apoptotic cascade in two of the most vulnerable brain regions--cerebral cortex and thalamus in time-dependent fashion by activating both Trk-dependent (in thalamus) and Trk-independent p75NTR dependent (in cerebral cortex) neurotrophic pathways. beta-estradiol, a sex hormone that upregulates the protein levels of the activated Akt, protects against anesthesia-induced neuroapoptosis.

show abstract

“…Most drugs have GABA-mimetic and/or NMDA antagonist properties, raising the question of whether combined use of sedative drugs has additive or synergistic neurotoxic effects (30,73). For example, coadministration of even low concentrations of ketamine and nitrous oxide synergistically enhances their neurotoxic effects (74). Sedative concentrations of midazolam and ketamine induce apoptosis in the infant mouse brain more effectively than either of these drugs alone (23).…”

Section: Experimental Data On the Effects Of Analgesics And Sedative mentioning

confidence: 99%

Use of Analgesic and Sedative Drugs in the NICU: Integrating Clinical Trials and Laboratory Data

et al. 2010

View full text Add to dashboard Cite

Recent advances in neonatal intensive care include and are partly attributable to growing attention for comfort and pain control in the term and preterm infant requiring intensive care. Limitation of painful procedures is certainly possible, but most critically ill infants require unavoidable painful or stressful procedures such as intubation, mechanical ventilation, or catheterization. Many analgesics (opioids and nonsteroidal anti-inflammatory drugs) and sedatives (benzodiazepines and other anesthetic agents) are available but their use varies considerably among units. This review summarizes current experimental knowledge on the effects of sedative and analgesic drugs on brain development and reviews clinical evidence that speaks for or against the use of common analgesic and sedative drugs in the NICU but avoids any discussion of anesthesia during surgery. Risk/benefit ratios of intermittent boluses or continuous infusions for the commonly used sedative and analgesic agents are discussed in the light of clinical and experimental studies. The limitations of extrapolating experimental results from animals to humans must be considered while making practical recommendations based on the currently available evidence.

show abstract

Ketamine potentiates cerebrocortical damage induced by the common anaesthetic agent nitrous oxide in adult rats

Cited by 84 publications

References 31 publications

Cognitive and Behavioral Outcomes After Early Exposure to Anesthesia and Surgery

Cognitive and Behavioral Outcomes After Early Exposure to Anesthesia and Surgery

General anesthesia activates BDNF-dependent neuroapoptosis in the developing rat brain

Use of Analgesic and Sedative Drugs in the NICU: Integrating Clinical Trials and Laboratory Data

Contact Info

Product

Resources

About