Hydroxyzine Dihydrochloride Premedication is a Necessity for Strabismus Surgery

Study Overview
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Brief Summary
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Oculocardiac reflex (OCR) is usually happening in pediatric strabismus surgery and observed just when the surgent pulls the ocular muscles. The reflex is one of the trigemino-vagal reflexes, and causes bradycardia, arrhythmia, and even cardiac arrest during eye surgery. Premedication for relaxation with drugs like hydroxyzine dihydrochloride or midazolam before surgery of the pediatric population is often used in Turkey, although it is not recommended in foreign countries. Some recent studies showed that when midazolam and hydroxyzine dihydrochloride used together not only, they lessen agitation before surgery but also they prevent emergence agitation. The primary aim of this prospective observational study is to show the effect of hydroxyzine dihydrochloride on preventing the pediatric patient from Oculocardiac reflex related to strabismus surgery.

Detailed Description
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Strabismus surgery is a frequently performed surgery in the Turkish population from one year of age to adults. Oculocardiac reflex(OCR) is the most recent complication happens during the operation, and it occurs approximately 20% to 80% according to its definition, in strabismus surgery. OCR is defined as the presence of dysrhythmia or a sudden heart rate decreased by 20% after traction on the extraocular muscles. OCR is one of the trigemino-vagal reflexes and causes bradycardia, arrhythmia and even cardiac arrest during eye surgery. To prevent patients from this complication the operator and anesthesiologist must cooperate during the operation because the first treatment is to stop traction of the muscle, the second one is to use atropine after diagnosing bradycardia. Oculocardiac reflex related trials were done for decades; searching for how and when it happens, which ocular muscles are related mostly, or which patients are at risk of OCR( age, heart rate related) are the most researched ones. According to our knowledge, there is no research about a premedication to prevent OCR during strabismus surgery. Before this study has planned by the investigator, the investigator had seen many OCR occurrence related to strabismus surgery, treated either with pausing the surgery or with atropin intravenous utilization in other clinics. After started working in this university hospital the investigator recognized those pediatric patients whom premedicated do not need to treat in the strabismus surgery because the OCR incidence was decreased dramatically. The investigator has planned this observational research at Yeditepe University Hospital because in this hospital pediatric patients receive variable oral premedication for sedation before surgery and for the prevention of emerging agitation. In Yeditepe University Hospital oral premedication( with variable drugs and variable doses) is nearly always ordered by anesthesiologists unless there is a comorbidity or allergy anamnesis related to the drugs planning to use. This current study is planned as observational. The investigator does not allow to give any orders about premedications or treatments before or during strabismus surgery. The Induction and the maintenance of anesthesia are also variable because there is no intervening to the anesthetist who performs anesthesia. The anesthetist who orders the premedication and performs anesthesia during strabismus surgery is not related to the trial and do not know the aim of the trial. The investigator is informed about the surgery on the day of the operation. The investigator and the patient's encounter before the study are about having the written consent form after explanation of the study. The only time to discriminate the patient from the study, by the anamnesis of the patient that is taken (about any comorbidities) during the encounter, according to the trials eligibility criteria if the patient and the patient has approved for including the trial. The investigator has even no permission to access the demographic data of the patient from the clinical papers which nurses have prepared because the investigator is not the anesthesiologist of the patient. Therefore the demographic data of the patient and the premedication performed to the patient is recorded after the operation retrospectively as the ethical committee approved. So, this current trial is not randomized, and there is no placebo group also, as a control group which is needed for an interventional one. Patients included to this trial were grouped after the end of the operation according to the premedication utilized, while the patient is awake in the service room after the operation, by having permission to access the demographic data and the premedication that had utilized before operation retrospectively. The prospective part of this study is planned to perform in the operation theatre observationally without knowing which premedication is utilized to the patient. In the operation theatre, the investigator observes the patient coming to the operation theatre and records the patients Ramsey Sedation Score before the operation starts. The heart rate 1, the heart rate 2 and the heart rate 3 data are planned to be recorded from the EKG monitorisation of the patient; in cooperation with the operator( the operator warns the investigator before the traction of the orbital muscle and informs about the name of the orbital muscle.). The investigator calculates the difference between the heart rate3 and heart rate2 and records if OCR occurred or not. If OCR occurred, the investigator observes and records how it is treated by the anesthesiologist in the operation theatre and the orbital muscle name which OCR occurred during its traction. The investigator is also not allowed to order any treatment about OCR during the operation. Because it is hard to plan this kind of an observational study the investigator had two years of paperwork to explain the planning of this observational study to be approved from both Yeditepe University Clinical Trials Ethical Committee, and from The Turkish Ministry of health, Turkish Medicines and Medical Devices Agency. A medical doctor from another clinic is charged with the monitorisation of this clinical trial by the ethical committee of the Yeditepe University whose identity is not known by the investigator. The primary aim of this prospective observational trial is to compare three different premedication methods observationally, to see if there is any difference in the OCR occurrence in strabismus surgery. The secondary aim is to compare the Ramsey Sedation Scores of the patients before surgery, the heart rates during the operation and their effect on OCR. The hypothesis is that; the pediatric patients premedicated with hydroxyzine dihydrochloride would be prevented from OCR during strabismus surgery because of the drug's side-effect of tachycardia while they are sedated before surgery as a positive effect.

Official Title
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Hydroxyzine Dihydrochloride Premedication is a Necessity for Pediatric Patients Undergoing Strabismus Surgery; An Observational Clinical Trial Controlled With Midazolam

Conditions
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Hydroxyzine, Strabismus, Reflex, Oculocardiac, Bradycardia Sinus

Intervention / Treatment
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* Drug: Midazolam
* Drug: Hydroxyzine Dihydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Strabismus, surgery needed Esotropia, surgery needed Exclusion Criteria: Chronic disease Arrhythmia Glaucoma(narrow-angle)

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Midazolam<br>Demizolam, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with cherry juice of maximum 5 ml. in Yeditepe University Hospital to the pediatric patients by the anesthesiologists. In all groups patients are not selected to the groups and premedication and doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively. | Drug: Midazolam<br>* Demizolam 15mg/ml ampules, given orally with cherry juice<br>* Other names: Zolamide,8680184750025,N05CD08;|
| Midazolam&Hydroxyzine dihydrochloride1/2<br>Midazolam and Hydroxyzine dihydrochloride, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with hydroxyzine dihydrochloride (dose of 0.5 mg/kg) in Yeditepe University Hospital to the pediatric patients by the anesthesiologists. In all groups patients are not selected to the groups and premedication doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively. | Drug: Midazolam<br>* Demizolam 15mg/ml ampules, given orally with cherry juice<br>* Other names: Zolamide,8680184750025,N05CD08;Drug: Hydroxyzine Dihydrochloride<br>* Atarax 2mg/ml syrup, given orally<br>* Other names: VALIDOL,8699705590019,N05BB01;|
| Midazolam&Hydroxyzine dihydrochloride<br>Midazolam and Hydroxyzine dihydrochloride, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with the maximum dose of 1mg/kg hydroxyzine dihydrochloride in Yeditepe University Hospital to the pediatric patients by the anesthesiologists. In all groups patients are not selected to the groups and premedication doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively. | Drug: Midazolam<br>* Demizolam 15mg/ml ampules, given orally with cherry juice<br>* Other names: Zolamide,8680184750025,N05CD08;Drug: Hydroxyzine Dihydrochloride<br>* Atarax 2mg/ml syrup, given orally<br>* Other names: VALIDOL,8699705590019,N05BB01;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart Rate-1 | The lowest heart rate observed from EKG monitorization at the time-out after the anesthesia induction, and just before the surgery starts. Heart rate-1 is a data, not an assessing change, which is recoded during the time-out. The time-out is when the patient's name, the procedure, the surgent name is repeated before the operation starts. | 1 minute, at the time out, through study completion an average of 6 months | 
| Heart Rate-2 | The heart rate observed from EKG monitorization at the time operator warns the investigator just before the traction of the orbital muscle. Heart rate-2 is a data, not an assessing change, which is recorded during the operation at the time operator warns. The heart rate observed from EKG monitorization, before every orbital muscle traction at the time the operator's warning before traction. | 1 minute, at the strabismus surgery operation, through study completion an average of 6 months | 
| Heart Rate-3 | The lowest heart rate observed from EKG monitorization, after every orbital muscle traction within 120 seconds. Heart rate-3 is a data, not an assessing change, which is recorded within 120 seconds after traction applied. | within 120 seconds after the orbital muscle traction, at the strabismus surgery operation, through study completion an average of 6 months | 
| Number of Observed Oculocardiac Reflex(OCR) | The OCR is a heartbeat anomaly(bradycardia, any arrhythmia, or cardiac arrest) associated with traction applied to the extraocular muscles during strabismus surgery. The specific criteria were as follows: the lowest heart rate observed within 120 seconds from EKG monitorization, after every orbital muscle traction, was less than 20% of the heart rate observed directly preceding traction of the orbital muscle. Additionally, any kind of arrhythmia or cardiac arrest occurrence within 120 seconds after orbital muscle traction was also defined as an OCR. | 2 minutes, at the strabismus surgery operation after recording Heart Rate-3, through study completion an average of 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ramsay Sedation Score | If Awake; Ramsay 1: Anxious, agitated, restless; Ramsay 2: Cooperative, oriented, tranquil; Ramsay 3: Responsive to commands only If Asleep; Ramsay 4: Brisk response to a light glabellar tap or loud auditory stimulus; Ramsay 5: Sluggish response to a light glabellar tap or loud auditory stimulus; Ramsay 6: No response to a light glabellar tap or loud auditory stimulus | After patient transferred into the operation theatre and before anesthesia induction, through study completion an average of 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Strabismus surgery, Oculocardiac reflex, Hydroxyzine dihydrochloride, Midazolam, Premedication, The Ramsay Scale