Determinants of the Pattern of Emergence From Anesthesia in Patients Undergoing Anterior Temporal Lobectomy and Amygdalohippocampectomy
Conditions: Emergence From Anesthesia
Sponsor: Lashmi Venkatraghavan

 
 
 
 
Determinants of the pattern of emergence from anesthesia in 
patients undergoing anterior temporal lobectomy and 
amygdalohippocampectomy 
 
 
ClinicalTrials.gov  
NCT02360098 
Date: 1 Dec 2014 
 
 
 
 
 
 
 
 
 
 
 
 
 

ClinicalTrials.gov  
NCT02360098  
Date: 1 Dec 2014 
2 
 
 
 
Determinants of the pattern of emergence from anesthesia in patients 
undergoing anterior temporal lobectomy and amygdalohippocampectomy 
Principal Investigator:   
Dr Lashmi Venkatraghavan, MD, FRCA, FRCPC  
Associate Professor, University of Toronto,  
Department of Anesthesia, Toronto Western Hospital, University Health Network,   
Phone: +1 (416) 603-5118   
Email: lashmi.venkatraghavan@uhn.ca  
 
Co-Investigators: 
Dr. Suparna Bharadwaj, MD  
Dr. Jigesh Mehta, MD  
Dr. Pirjo Manninen, MD 
  
Introduction  
Smooth and quick emergence (wake up) from anesthesia is an important consideration in patients 
undergoing neurosurgical procedures as blood pressure changes associated with violent 
emergence can cause intracranial hemorrhage and brain swelling. Delirium and agitation can be 
dangerous and have serious consequences for the patient such as injury, increased pain, 
hemorrhage, selfextubation and removal of catheters requiring physical or chemical restraint. On 
the other hand, the unarousable patient may pose dangerous airway complications and limit 
neurological assessment in the immediate postoperative period.   
Epilepsy surgery involves resecting epileptogenic tissues including limbic structures which may 
be functionally normal. Hence the emergence process can be complicated in patients having 
diseased limbic structures or those having therapeutic removal of limbic structures as in epilepsy 
surgery. Limbic structures are responsible for memory, language and executive function and 
hence loss of some of these higher functions is to be expected in the postoperative period. 
Preoperative neuropsychological assessments are often used to predict their risk for 
postoperative loss of higher functions and behavior changes. In our experience the investigators 
have seen that there is a spectrum of emergence characteristics in patients undergoing temporal 
lobectomy that can vary from dangerously agitated patient to much sedated, unarousable patient. 
Delirium and agitation can be dangerous and have serious consequences for the patient such as 
injury, increased pain, hemorrhage, self-extubation and removal of catheters requiring physical 
or chemical restraint. On the other hand, the unarousable patient may pose dangerous airway 
complications and limit neurological assessment in the immediate postoperative period. Hence it 
is essential to have a clue about post anesthesia emergence behavior in patients having epilepsy 

ClinicalTrials.gov  
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Date: 1 Dec 2014 
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surgeries. The aim of this study is to look at the pattern of emergence from anesthesia after 
epilepsy surgery and to determine if preoperative neuropsychological assessment help predict the 
pattern of emergence in patients undergoing anterior temporal lobectomy and 
amygdalohippocampectomy. 
Background 
Emergence from anesthesia starts with activation of deep brain structures namely subcortical and 
limbic regions of the brain.  Later they become functionally coupled with other parts of brain 
including frontal and inferior parietal cortex. Arousal (spoken command) induced brain 
activations during emergence from anesthesia are mostly localized in deep, phylogenetically old 
brain structures (limbic cortex or mesial temporal structures) than in neocortex.1  
Physiologically, when emerging from deep anesthesia there will first be signs of autonomic 
arousal, followed by a slow return of brainstem reflexes, eventually leading to reflexive or 
uncoordinated movements that occur somewhat before subjects can willfully respond to simple 
commands. Thus, emergence of a conscious state, precedes the full recovery of neocortical 
processing required for establishing contact with the surroundings.  The prevalence of epilepsy is 
around 0.4–0.8%2 and 20–30% of these patients will develop medically refractory seizures2-4 and 
hence present for surgical treatment.  
Epilepsy surgery involves resecting epileptogenic tissues including limbic structures which may 
be functionally normal. Anterior temporal lobectomy and amygdalohippocampectomy is a well-
established surgical treatment for the patients with temporal lobe epilepsy and these parts of the 
brain have a role in the emergence from general anesthesia. Due to asymmetry of temporal 
neocortical (dominant vs nondominant) and mesial temporal functional representations, the loss 
of these structures and hence their functions in the postoperative period complicates emergence 
from anesthesia in these patients3.  Preoperative neuropsychological assessments are often used 
to predict the risk for postoperative loss of higher functions and behavior changes. 
Rationale 
There are no study related interventions in this study and perioperative care of these patients will 
be as per our standard practice. The only study related protocol would be collecting the data on 
the emergence from anesthesia. The data will be collected from the time of turning off the 
anesthetic agents till the discharge from recovery room. Data collected include, vital signs, 
Glasgow coma scale (GCS), and Riker agitation- sedation score. The patients will be assessed 
every 5 minutes for the first 30 minutes and every 10 minutes for the next 60 minutes. 
Study Objective and Hypothesis   
The aim of this study was to look at the pattern of emergence from anesthesia after epilepsy 
surgery and to determine if preoperative neuropsychological assessment help predict the quality 
of emergence in patients undergoing anterior temporal lobectomy (ATL) and 
amygdalohippocampectomy (AH).  

ClinicalTrials.gov  
NCT02360098  
Date: 1 Dec 2014 
4 
 
We hypothesized that there will be a relationship between preoperative neuropsychological 
assessment scores and the limbic structure (hippocampus, amygdala and thalamus) volumes with 
the quality of emergence from anesthesia in patients undergoing anterior temporal lobectomy and 
amygdalohippocampectomy.   
Study Design 
This prospective, observational study will be conducted after approval from institutional ethics 
board and written informed consent will be obtained from each subject.  
Eligibility Criteria 
Inclusion Criteria: 
  -  Adult patients above the age of 18 who are scheduled for elective anterior temporal 
lobectomy and amygdalohippocampectomy under General Anesthesia 
Exclusion Criteria: 
- Lack of informed consent 
- Patients needing intensive care unit postoperatively 
 
Study Procedure  
Standard perioperative management   
Anesthesia and neurosurgical care of the patients is as per the standard institutional practice. 
Preoperatively all patients will be seen by the anesthesiologists in the pre-anesthesia consult 
clinic.  
Intraoperatively, all patients will have standard monitoring consisting of electrocardiography 
(ECG), pulse oximetry, end–tidal carbon dioxide (ETCO2), invasive and non-invasive blood 
pressure, temperature, urine output, depth of anesthesia (Entropy) and end tidal anesthetic agent 
concentration.  
Anesthesia induction will be with propofol (1-2 mg/kg), fentanyl (2-3mcg/kg) and rocuronium 
(0.8-1.2mg/kg).  
Anesthesia will be maintained with oxygen, air, sevoflurane (0.8-1 MAC (Minimal Alveolar 
Concentration)) and remifentanyl infusion titrated to keep entropy within 45-55.   
After induction and positioning, the surgery (ATL and/or AH) will be proceeded as per standard. 
After dural closure, inhalational agent concentration will be decreased gradually to MAC of 0.6 
and fentanyl 1-2mcg/kg administered for additional analgesia.  
After the closure of scalp, inhalational agent will be turned off. 
Remifentanyl infusion will be turned off once the head is disengaged from head pins and after 
completion of the head dressing.  
The patients will be allowed to wake up with “no touch technique”.  

ClinicalTrials.gov  
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Date: 1 Dec 2014 
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Extubation will be done when the patients are breathing adequately, spontaneously and obeying 
commands.  
Post-surgery, patients recovered in the post anesthesia care unit (PACU) before being discharged 
to the neurosurgical critical care unit.   
Data Collection 
Data will be collected from the time of turning off the anesthetic agents till the discharge from 
recovery room.  Patients will be assessed every 5 minutes for the first 30 minutes and every 10 
minutes for the next 60 minutes. Data collected will include patient demographics, preoperative 
neuropsychological assessment data, Age, Intelligence quotient (IQ), Verbal, visual, language 
memory , education, History of psychiatric illness, Dexterity of the patient and side of surgery, 
Time of emergence from anesthesia, Vital signs, Glasgow Coma Scale (GCS) score, and Riker 
agitation score  (7-agitated;dangerous agitation, 6-very agitated, 5-agitated, 4-nonagitated;calm 
and cooperative, 3-sedated but arousable, 2-very sedated, 1-unarousable ). 
Data Analysis  
There are no previous studies looking at the emergence characteristics in patients with temporal 
lobectomy. As this is an observational study, there are no cause effect relationship to calculate 
sample size.  Emergence characteristics were classified as either smooth emergence (Riker scale 
3-4) or agitated emergence (Riker scale >4).  Correlation coefficients will be used to compare the 
data between preoperative neuropsychological scores and the emergence characteristics (smooth 
vs. agitated) and the time of emergence. Quantitative variables like hemodynamics will be 
analyzed using student`s t-test. Qualitative variables like sex distribution will be analyzed using 
Chi-square test. A p-value less than 0.05 is considered significant.  
CONCLUSION 
Smooth emergence (wake up) from anesthesia is an important consideration in patients 
undergoing neurosurgical procedures as blood pressure changes associated with violent 
emergence can cause intracranial hemorrhage and brain swelling. At the same time, emergence 
should also be quick so that patients' neurological function can be assessed at a timely manner. 
Pattern of emergence from anesthesia is poorly investigated and understood.  
REFERENCES  
1. Jaakko W. Långsjo, Michael T. Alkire, et al. Returning from Oblivion: Imaging the Neural 
Core of Consciousness. The Journal of Neuroscience. 2012; 32:4935– 4943  
2. Hauser WA, Rich SS, Annegers JF, et al. Seizure recurrence after a 1st unprovoked seizure: an 
extended follow-up. Neurology 1990;40: 1163–70.  
3. Gilliam F. The impact of epilepsy on subjective health status. Curr Neurol Neurosci Rep 2003; 
3:357–62  

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Date: 1 Dec 2014 
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4. Friedman EB, Sun Y, Moore JT, et al. A conserved behavioral state barrier impedes transitions 
between anesthetic-induced unconsciousness and wakefulness: evidence for neural inertia. PLoS 
One. 2010; 5: e11903.