1-A study to compare the contribution of inhaled anesthetic agents to emergence agitation,
showed an increased incidence of emergence agitation with sevoflurane anaesthesia compared
to halothane independent of any painful stimulus.
2-Davis et al., found a 15 %incidence of agitation in children who received halothane, but
more than 50 %of children who received desflurane anaesthesia experienced agitation.
3-Children receiving midazolam preoperatively had an almost nine-fold higher risk of
developing postoperative delirium than those who did not receive midazolam.
4-Possible causes of EA include rapid awakening in unfamiliar settings, pain (wounds, sore
throat, bladder distension, etc.), stress during induction, hypoxemia, airway obstruction,
noisy environment, anesthesia duration, child’s personality, premedication and type of
anesthesia. Prolonged Episodes of agitation lasting for up to 2 days have been described.
5-Since anesthesia depresses central nervous system inhibitory centers and causes
imbalances in neurotransmitters such as serotonin and dopamine and acetylcholine, it too
may contribute to the appearance of this adverse event. Other inhaled anesthetics, such as
desflurane and isoflurane, have also been inked with the occurrence of emergence agitation.
6-Sevoflurane, isoflurane and desflurane all induce similar electroencephalographic changes
during anesthesia, which are different to those provoked by halothane. This fact might
explain the low incidence of agitation when patients are anesthetized with halothane.
7-Elevated lactate and glucose concentrations in the parietal cortex due to sevoflurane
anesthesia, and the occurrence of clinically silent sevoflurane-induced epileptogenic
activity have been proposed to induce EA .
8-Studies have reported that alterations of brain network connectivity vary with the level of
sedation. During emergence from general anesthesia, thalamocortical connectivity in sensory
networks, and activated midbrain reticular formation are preserved. However, delayed recovery
of impaired functionality of subcortical thalamo -regulatory systems could contribute to defects
in cortical integration of information, which could lead to confusion or an agitated state .
9-To Prevent Emergence Agitation : (A-Pharmacological methods ):
Total intravenous anesthesia -Propofol -Opioids -Ketamine -Magnesium sulfate -Tramadol
Nefopam- Dexmedetomidine -Regional analgesia -Multimodal analgesia - Avoidance of
premedication with benzodiazepines (especially in adults).
(B-Non-pharmacological methods): Informing the patient of predictable pain or discomfort prior
to anesthesia - Removing indwelling invasive devices as early as possible -Parental presence
during induction of anesthesia and recovery (in pediatric patients) -Family-centered behavioral
preparation for surgery .
10-Differential diagnosis and prompt treatment should also be performed for conditions that
can lead to disorientation, such as increased intracranial pressure, bladder distention, upper
airway obstruction, hypo- and hyperglycemia, hypotension, hypoxia, and hypercarbia .
11-The Mdoloris Anaesthesia Nociception Index (ANI) monitor (Mdoloris Medical Systems, Lille,
France) is a computer-based ECG monitor that does beat-to-beat analysis of heart rate
variability ( HRV) for adequate analgesia. It evaluates HRV via signals from two separate monitor
electrodes placed on the patient’s chest. The Narcotrend (NCT) EEG monitor (Monitor Technik,
Bad Bramstedt, Germany) measures brain wave activity. With increasing depth of anaesthesia,
the brain wave activity follows a similar brain wave pattern as during normal sleep. Reduced
propofol consumption and tight correlation with end tidal sevoflurane have been
12-Emergence delirium (ED) was first described in the literature in the early 1960s.In the longer
term, children with ED are 1.4 times more likely to have new onset of maladaptive behavioural
changes (sleep disturbance, separation anxiety, eating disturbance) for up to 2 weeks after
surgery. Failure of a child to make eye contact who is also unaware of his or her surroundings is
more likely consistent with ED. Abnormal facial expression, inconsolability and crying while the
patient is making eye contact and is aware of his or her surrounding is more likely from pain.
13-Intranasal dexmedetomidine 1-3 µg·kg administered preoperatively was found to reduce
the incidence of ED. Gabapentin may be an effective prophylactic in children, although it has not
been shown to be effective in adults. Acupuncture may be an important technique in decreasing
ED. A double-blind, randomised controlled trial in Japan showed a decrease in ED in paediatric
patients who received an electrical stimulation on the heart 7 (HT7) acupuncture site with a
peripheral nerve stimulator. Video distraction has also been shown to be as effective as an
anxiolytic as parental presence.
14-The highest incidences of excitement were correlated with the ‘youth of the patient, the
excellence of his health, barbiturate and scopolamine pre- anaesthetic medication,
cyclopropane or ether anaesthesia and operative procedures associated with pain or emotional
stress’. The Face, Legs, Activity, Cry, Consolability (FLACC) scale and the Paediatric Anaesth
Emergence Delirium (PAED) scale have been applied in efforts to differentiate between ED and
pain in children 2–6 yr of age after tonsilectomy, adenoidectomy, or both. Inconsolability and
restlessness were not reliable enough to differentiate between the two in the early
postoperative period. 15-The PAED scale, developed in 2004 for children >2 yr of age. A
prospective randomized controlled trial of children (1–12 yr of age) undergoing magnetic
resonance imaging with a laryngeal mask airway with sevoflurane, showed a decreased
incidence of EA when sevoflurane was transitioned to propofol 3 mg/ kg (via divided bolus)
before emergence. 16- ED has not been carefully examined for longer-term consequences.
16-Epileptiform EEG events were common in children during sevoflurane anesthesia. The low
initial concentration technique and shorter exposure time of sevoflurane may be associated
with a decreased occurrence of these paradoxical discharges. More studies are needed to
confirm these findings.
17-Central CNS stimulation of parasympathetic outflow and inhibition of sympathetic outflow
from the locus cereleus in the brainstem play a prominent role in the sedation and anxiolysis
produced by these agents. Decreased noradrenergic output from the locus cereleus allows for
increased firing of inhibitory neurons including gamma amino butyric acid (GABA). Primary
analgesic effects and potentiation of opioid-induced analgesia result from the activation of α2-
adrenergic receptors in the dorsal horn of the spinal cord and the inhibition of substance P
18-Melatonin :Preoperative oral administration of melatonin (0.2 or 0.4 mg kg−1), despite it
having no effect on preoperative anxiety, has been shown to have greater benefits than
midazolam 0.5 mg orally in decreasing incidence of emergence delirium. A dose-dependent
effect was found. The incidence of ED was 25.6% with midazolam and 8.3 and 5.4% with
melatonin 0.2 and 0.4 mg kg−1, respectively.
19-Children who received sevoflurane/isoflurane for the
induction/maintenance of anesthesia were twice as likely
to develop EA when compared with children who had
any other anesthetic regimen.
20-Failure to find a link between minutes under deep
anesthesia (BIS <45) and EA was noted.
21-In children, agitation during sevoflurane induction
can be reduced by optimizing the preoperative
preparation (as for any technique of induction),
administering a sedative premedication, using a high
inspired concentration of sevoflurane in 50% N2O.
22-Severe emergence agitation might be related to a
central anticholinergic syndrome as diagnosed
empirically with a successful treatment with
23-The incidence of sevoflurane-induced
emergence agitation was significantly lower in
children premedicated with a midazolam and
hydroxyzine combination compared to those
premedicated with midazolam only.
25-The application of DEX added to the LIDO
local anesthesia cartridge was found to
significantly benefit anxious patients with
previous unpleasant dental treatment
*** p-value < 0.05 means that the null
hypothesis is rejected and the distribution is
***When the sample size is small,
there are only a few independent
pieces of information, and therefore
only a few degrees of freedom.
When the sample size is large, there
are many independent pieces of
information, and therefore many
degrees of freedom.