Effect of Monochromatic Light on Incidence of Emergence Delirium in Children
Phase: NA
Conditions: Emergence Delirium, Anesthesia Emergence Delirium
Sponsor: Baylor College of Medicine

Title: EFFECT OF MONOCHROMATIC LIGHT ON THE INCIDENCE OF EMERGENCE 
DELIRIUM IN CHILDREN; A SINGLE BLINDED RANDOMIZED CONTROLLED TRIAL 
 
Protocol ID#: H-39878 
Drafted 9/8/17 
IRB submit 8/15/17 
Collaborators:  
Adam C. Adler, MD, MS- Principle Investigator  
Arvind Chandrakantan, MD, MBA, FAAP 
 
Background: 
 
Emergence delirium/emergence agitation (ED/EA) is a behavioral phenomenon of unclear 
etiology consisting of short lived behavioral changes that can be both traumatic to families and 
pose a safety risk to patients and staff. ED is characterized by a variety of presentations, 
including crying, excitation and agitation, that occur during the early stage of recovery 
from general anesthesia, generally in the first 30 minutes.  
Involuntary activity in the bed and even thrashing about during an episode of ED can lead to 
dislodgement of IV cannulas, surgical dressings and or surgically placed items such as drains and 
catheters.  
Emergence delirium occurs in children of all ages following an anesthetic with halogenated 
agents (e.g. sevoflurane/isoflurane) with or without having undergone a surgical procedure (e.g. 
MRI patients). Electroencephalograms (EEG) in patients experiencing emergence delirium show 
diffuse background slowing.  Presently, the treatment for ED is to revert the patient back to a 
hypnotic state mainly with sedatives so that they may “reset” themselves postulating that by re-
inducing a hypnotic state, the brain has time to resolve this issue. The hypothesis of this study is 
that during ED, there is failure of organized EEG activity, especially alpha wave activity and that 
by enhancing alpha activity, the incidence of ED may be reduced without the need for additional 
pharmaceuticals which may be costly, delay recovery and are not without adverse effects 
specifically cardiopulmonary depression.   
 
Monochromatic light (ML) has been used in a variety of clinical and non-clinical applications to 
affect a variety of changes. Exposure to light of short wavelength within the visible spectrum 
(450-470nm) has been associated with effects on circadian rhythm, neuroendocrine and 
neurobehavioral changes and enhanced cognitive performance. Blue ML has been studied safely 
to enhance work-place alertness and productivity. Clinically, blue ML has been used safely for 
decades in the neonatal intensive care unit to treat jaundice.  
 
Blue ML, has been known to suppress melatonin secretion and enhance alertness and workplace 
performance. The effect occurs within the retinal photoreceptive ganglion cells which mediate 

the observed responses. The effect is even present in visually blind persons lacking outer retinal 
function. Short exposure to bursts of blue light has revealed enhanced neural activity on 
functional MRI. Use of blue ML has been shown to enhance EEG activity in the alpha range 
(awake range) compared with light of greater wavelengths. If using blue ML in the operating 
room may enhance alpha EEG activity, (a circadian marker for alertness) it may be possible to 
reduce the incidence of emergence delirium in the post-operative period and therefore the 
amount of (non-pain) sedative medication needed in recovery.  
 
Purpose: 
 
Emergence delirium is associated with a safety risk to patients and staff members in the fact that 
these children are uncontrollable and often thrashing which may result in self-inflicted injury 
(falls and collision with bedframe) or perturbation of intravenous or surgically placed devices. At 
present, the treatment involves re-sedating these patients (e.g. propofol or dexmedetomidine). 
These medications are certainly not without risk. If intravenous access has been lost, intra-nasal 
or intra-muscular administration of medications can be dangerous or impractical to administer at 
times of delirium.   
 
The primary aim of this study is to ascertain if perioperative exposure to non-invasive 
monochromatic blue light can reduce the incidence of emergence delirium. 
 
The secondary aim involves assessing the need for rescue interventions (e.g. hypnotic agents – 
propofol or dexmedetomidine).  
 
Protocol/Risk/Subjects: 
 
Patient identification 
Patients ages 2-6 years undergoing routine tonsillectomy and adenoidectomy requiring general 
anesthesia would be identified for inclusion. Exclusion criteria would include: American Society 
of Anesthesiology classification other than 1,2; history of migraine headaches, ocular disorders, 
seizure history, psychiatric conditions, parental refusal, developmental delay and those patients 
on medication for attention deficit disorders or caffeine stimulants. Patients with 
contraindications to receiving inhalation agents, use of premedication with midazolam or 
dexmedetomidine would also be excluded.  
 
Randomization 
After enrollment and consent, each patient will be randomized to either placebo or intervention 
group. 110 sealed envelopes randomizing patients to the exposure group A (monochromatic 
light) or bulb B (placebo) white light bulb with blue outer coating.  
 

The machine used for the study will be the Drager Photo-Therapy 4000 currently in use through 
the NICU at Texas Children’s Hospital. The bulb is the standard Drager approved Osram Dulux 
18W/830 commercially available bulb. This bulb produced light of 450-470nm wavelength, well 
within the visible spectrum. The protective plexi shield will remain in place. The bulb for the 
placebo group contains white florescent bulbs Osram Dulux 18W/830 with a blue plastic 
covering that will produce light containing all wavelengths in the visible spectrum but will 
appear blue due to the outer cover. To ensure that this bulb does not produce any monochromatic 
light, a calibration meter, (Solarmeter Model 9.4 Blue Light Meter measuring 422-499nm with 
range from 0-199.9 mW/cm² Blue Light) will be used. 
 
Patients will be evaluated for emergence delirium by two nurses blinded to the study arm.  
 
Each patient will be given a study specific number for de-identification of data avoiding use of 
any identifiers (name, DOB, MRN, date of service etc.).  
 
 
Anesthetic Description  
A standard and routine anesthetic will ensue for these patients in line with routine operative 
practices at Texas Children’s Hospital, including an inhalational induction (mask) using 
sevoflurane 8%v/v with oxygen/nitrous oxide 3/7 L/min respectively, followed by intravenous 
cannula placement. Propofol will be administered if needed to facilitate oral endotracheal 
intubation at the discretion of the anesthesia attending. Dexamethasone (0.5mg/kg), ondansetron 
(0.1mg/kg) and morphine (0.1-0.2mg/kg) will be administered for anti-inflammatory, antiemetic 
and analgesic effects respectively. Intravenous fluid (lactated ringer solution) will be 
continuously infused with the appropriate volume to be determined by the anesthesia provider. 
Maintenance of anesthesia will be with sevoflurane with the concertation titrated to maintain an 
appropriate level of hypnosis as determined by the anesthesia provider. At the conclusion of the 
surgery, the patient will undergo routine deep extubation according to the routine practice of the 
anesthesia providers of record. On arrival to the PACU, the Drager phototherapy lamp will be 
illuminated over the patients head and neck. Randomization will determine if the patient will be 
exposed to ML blue light or the placebo bulb (white bulb with blue over coating). The PACU 
staff and the anesthesiologist will be blinded to study arm. The placebo bulb will provide blue 
light of all wavelengths as to not compromise blinding. The light will remain active and over the 
patient until the patient has been in the post anesthesia recovery unit (PACU) for 30 minutes.  
 
Postoperative evaluation for emergence delirium 
Two PACU nurses blinded to the patient group will be asked to complete the PAED scoring 
scale for evaluation of emergence delirium. They will be asked to complete the scoring 
evaluation upon arrival to the PACU and at 10 minutes, 20 minutes and 30 minutes following 
arrival. Two nursing evaluations will be used to reduce inter-observer bias. A patient 

experiencing emergence delirium will receive standard pharmacologic treatment as determined 
by the anesthesiology provider irrespective of study participation. Blinding of the nurse and 
anesthesia team will help to ensure that the nursing staff will call the anesthesia providers with 
any and all usual questions and the anesthesia provider to react and treat potential ED as per 
usual practice without being biased by the study.  
The study will end at this point without the need for additional follow-up or patient contact 
related to the study. 
Statistical Analysis Plan  
 
Sample size/Data Analysis:  
 
The PAED behavioral scale will be used to assess the incidence of emergence delirium. The 
PAED scale is a reliable tool to measure ED and involves five items: eye contact, purposeful 
actions, awareness of the surroundings, restlessness, and inconsolability. While other scales 
exist, the PAED scale is the standard for assessment of ED and is the only validated scale. A 
PAED score of >12 will be used to define ED.  
Cohort means and standard deviations (SD) or counts and frequencies as appropriate for the 
variables collected. We will compare the blue light and Sham groups using the Student’s t-test 
for continuous variables (e.g., age, PAED score) and the chi-square test for categorical variables 
(e.g. % female, ASA category). For counts < 5, the Fisher’s exact test will be used.  For baseline 
comparisons, absolute standardized differences instead of p-values will be used to compare the 
groups.  
Given the prospective collection of data, missing data for the PAED scores over time indicated a 
patient woke up or experienced emergence delirium and so no imputation will be performed. To 
adjust for any remaining confounding among the variables collected, a logistic regression model 
with the outcome being emergence delirium and a second logistic regression model with the 
outcome being either ED or the patient had a PAED score of 12 or more at time periods 10, 20, 
and 30 min. Both regression models used as independent predictors the following variables: 
treatment group, age, weight, gender, and ASA category. Robust standard errors were derived to 
account for any within-cluster correlation at the individual nurse level given the possible serial 
correlation of outcomes within each nurse caring for his or her patients.  
An a priori calculation of sample size was done using an incidence of 40% of emergence 
delirium in similar patient population. We assumed an absolute reduction of 25% (ie, 40% to 
15%) in incidence of emergence delirium to be clinically significant. To detect this difference at 
80% power with a two-sided alpha of 0.05, required a sample size of 98 participants.  
 
All p-values < 0.05 were considered statistically significant. 
 
Risk/Discomfort: 
 
The study procedure poses no additional risk to patients. The major risk is loss of confidentiality.  

Use of monochromatic light has been safely tested in numerous human studies and used 
routinely in the NICU without identified patient risk using the same Drager machines at TCH.  
The moment the patient is awake and making purposeful eye contact with the PACU RN, the 
lights will be terminated. The risk of phototherapy is well known from nearly 40 years of clinical 
use in neonates. The risk of phototherapy is predominantly in neonates, especially preterm 
infants with jaundice, all requiring prolonged and continuous exposure to high intensity light for 
many days. This study will not include any neonates (with immature retina) or long term 
exposure of >30 min. The study will be terminated the moment the patient is awake and making 
purposeful eye contact with the PACU RN to avoid unnecessary discomfort.  
 
Benefits: 
The study benefits include improved understanding of emergence delirium and potential for both 
reduction in the incidence of emergence delirium and the use of pharmacologic agents.  
 
Consent procedures: 
The parental or legal guardian permission form will be signed prior to the beginning of surgery.  
 
Confidentiality: 
Personal Health Information(PHI) will be safeguarded at all times. Patients will be assigned a 
study ID number; their name or other identifying information will not be used in any 
presentations or publications resulting from this research.  Data will be kept in a locked office to 
which only departmental personnel have access.  Data files will be stored on a secure hospital 
network drive. 
 
 
Sample collection: 
Patients will be enrolled prospectively and randomized to either study or placebo arms. In 
addition, each patient will be assigned a random non-identifiable study number to ensure 
anonymity. 
The following information will be recorded:  
Age in months, gender, duration of procedure, duration from induction to extubation,  
Recovery time (defined as arrival in PACU to first spontaneous eye opening or response to 
verbal command)  
PAED behavioral scoring sheet will be completed at: (T=0 on PACU arrival, 10, 20 and 30 
minutes post PACU arrival). Nurse determination of occurrence of ED.  
Administration of supplemental dexmedetomidine, propofol, opioid or benzodiazepine in PACU 
will be noted if given. Opioid given to treat pain will be noted as such.  
 
 
References: 

 
Sikich N, Lerman J: Development and psychometric evaluation of the Pediatric Anesthesia Emergence Delirium 
Scale.  Anesthesiology 2004; 100:1138-45. 
Deiner S, Silverstein JH. Postoperative delirium and cognitive dysfunction. Br. J. Anaesth 2009 103 (suppl 1): i41-
i46. 
Zeitzer JM, Dijk DJ, Kronauer R, Brown E, Czeisler C. Sensitivity of the human circadian pacemaker to nocturnal 
light: melatonin phase resetting and suppression. J Physiol 2000;526 Pt 3:695-702. 
Hébert M, Martin SK, Lee C, Eastman CI. The effects of prior light history on the suppression of melatonin by light 
in humans. J Pineal Res 2002;33(4):198–203. 
Rahman SA, Flynn-Evans EE, Aeschbach D, Brainard GC, Czeisler CA, Lockley SW. Diurnal spectral sensitivity of 
the acute alerting effects of light. Sleep 2014;37(2):271-81. 
Viola AU, James LM, Schlangen LJ, Dijk DJ. Blue-enriched white light in the workplace improves self-reported 
alertness, performance and sleep quality. Scand J Work Environ Health 2008;34(4):297-306.  
Bajwa SA, Costi D, Cyna AM. A comparison of emergence delirium scales following general anesthesia in children. 
Paediatr Anaesth 2010;20(8):704-11.  
Vandewalle G, Collignon O, Hull JT, Daneault V, Albouy G, Lepore F, Phillips C, Doyon J, Czeisler CA, Dumont 
M, Lockley SW, Carrier J. Blue light stimulates cognitive brain activity in visually blind individuals. J Cogn 
Neurosci 2013;25(12):2072-85.  
Vandewalle G, Schmidt C, Albouy G, Sterpenich V, Darsaud A, Rauchs G, Berken PY, Balteau E, Degueldre C, 
Luxen A, Maquet P, Dijk DJ. Brain responses to violet, blue, and green monochromatic light exposures in humans: 
prominent role of blue light and the brainstem. PLoS One 2007;2(11):e1247. 
Watcha MF, Ramirez-Ruiz M, White PF, Jones MB, Lagueruela RG, Terkonda RP. Perioperative effects of oral 
ketorolac and acetaminophen in children undergoing bilateral myringotomy. Can J Anaesth 1992;39(7):649-54.