Effect of Dexmedetomidine on the Minimum Alveolar Concentration of Sevoflurane

The anesthetic potency of an inhalational anesthetic is measured by the minimum alveolar
concentration (MAC), or the dose required to suppress movement to a surgical stimulus in 50%
of patients. This measure of potency may also be used to assess the effects of other agents
on the MAC of the inhalational agent. Sedative agents reduce MAC of inhalational anesthetic
agents. Two human adult studies have shown that Dexmetomidine decreased the minimum alveolar
concentration of Isoflurane and Sevoflurane. Age has an important effect on the MAC of
inhalational anesthetics in children. Sevoflurane is a commonly used polyflourinated methyl
ether with a low blood:gas partition coefficient, which facilitates a rapid increase in
alveolar and tissue anesthetic partial pressures and subsequent rapid emergence from
anesthesia. Additionally, Sevoflurane is non-stimulating to airway reflexes facilitating
smooth inhalational induction of anesthesia. The MAC of Sevoflurane is also dependent on age
with the MAC in neonates (<28 days) 3.3%, infants between 6-12 months of age 3.2%, and
infants 6-12 months of age and children 1-12 years of age 2.5%. MAC is affected by several
factors. Hypothermia, hyponatremia, hypo-osmolality, metabolic acidosis, hypoxia,
hypercarbia, anemia, pregnancy, nitrous oxide, opioids, propofol, benzodiazepines, and acute
alcohol use decrease MAC whereas hyperthermia, cocaine, amphetamines, hypernatremia, chronic
alcohol use increase MAC. Dexmetomidine is an alpha-2 agonist that has been used as a
premedication, an adjunct to analgesia, and an adjunct to general inhalational anesthesia.
Alpha-2 adrenergic agonist additionally decease the stress response to surgery. Alpha-2
adrenergic agonists have sedative, hypnotic, and analgesic properties and have been reported
to decrease the amount of other sedative, analgesic, and general inhalational anesthetics in
not only animal studies but also human studies. A concentration-response relationship has
been reported in adults receiving Dexmedetomidine using the visual analog scale (VAS)
sedation scale (0-100) with a 0 as very alert and 100 as very sedated. A score of 40
correlated with a Dexmedetomidine concentration of 0.7mcg/mL and a score of 60 with a plasma
concentration of 1.2mcg/mL. The sedated target concentration from a pooled population of
children and neonates has been reported to be between 0.4 and 0.8 mcg/mL. Additionally, a
plasma concentration of 0.6mcg/mL has been estimated as satisfactory for sedation in the
adult ICU. Inhalational anesthetics have been shown to cause neuroapoptosis and
neurodegenerative changes in various animal models; however, the human data from
retrospective and epidemiologic studies in children exposed to inhalational anesthetics is
inconclusive. There are ongoing trials to determine the effect of exposure from inhalational
anesthetics on neurodevelopment outcomes. There is emerging evidence that Dexmedetomidine is
not associated with neuroapoptosis or other neurodegenerative changes. Dexmedetomidine has
actually been shown to attenuate Isoflurane-induced neurocognitive impairment in neonatal
rats. There is no information regarding the reduction of MAC of Sevoflurane in children with
clinically applicable Dexmetomidine dosing regimens. Additionally, determining the degree of
reduction of Sevoflurane MAC by Dexmedetomidine may be helpful in providing an alternative
anesthetic regimen such as the routine use of Dexmedetomidine and Sevoflurane in order to
decrease the potential neuroapoptotic effects of inhalational anesthetic agents.

Exclusion Criteria:

1. Interstitial lung disease, chest wall disease, or bronchospastic disease with no
flare-ups in the past 2 weeks of presentation

2. History of difficult intubation or ventilation

3. Airway malformation

4. Congenital heart disease

5. Cardiac arrhythmias

6. Central nervous system disease, including developmental delay, cerebral palsy, or
seizure disorder

7. History of or family history of malignant hyperthermia

8. Electrolyte disorders

9. Gastrointestinal disease

10. Hepatic dysfunction

11. Renal dysfunction

12. Metabolic disease, such as diabetes

13. Obesity, defined as a body mass index greater than the 95% percentile for age

14. Preterm infant (less than 37 weeks gestational age) 15. Use of any medications
(anticonvulsants, opioids, benzodiazepines, antibiotics, antihistamines drugs that
induce hepatic enzymes) that may affect MAC.

Inclusion Criteria

All patients age 1 month- 3 years presenting for surgery.