Sedation Complications in Urology During Spinal Anesthesia With Dexmedetomidine or Midazolam Regarding OSA Risk

Study Overview
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Brief Summary
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Light to moderate sedation is recommended during surgery with spinal anesthesia . This study is exploring which sedation drug is better, midazolam or dexmedetomidine for transurethral resection of bladder and prostate in patients with or without high risk for obstructive sleep apnea (OSA). Patients were divided in two groups regarding OSA risk, and each group received midazolam or dexmedetomidine for sedation. Investigators observed intraoperative complications of airway and factors that are disturbing surgeon(movement due to participants coughing and restlessness) because one could puncture bladder or prostate and cause perforation.

Detailed Description
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All participants were premedicated with diazepam 5mg 12 hours and 1 hour before surgery. Thromboprophylaxis (enoxaparin 4000-6000 IU) depending on the body weight was given at least 12 hours before surgery. Participants were divided by STOP-BANG(Snoring history, Tired during the day, Observed stop breathing while sleep, High blood pressure, BMI more than 35 kg/m2, Age more than 50 years, Neck circumference more than 40 cm and male Gender) questionnaire into one of two groups: high OSA and low&medium OSA. Each group was then allocated by permuted block randomisation into midazolam or dexmedetomidine group. The randomisation list was obtained from R program. The group allocations were contained in closed envelope that were opened before surgery after the completed enrollment procedure. Participants got IV cannula with switch for continuous intravenous infusion in operating theatre. Non invasive monitoring (electrodes for ECG, blood pressure cuff and pulse oximeter) was placed before induction of spinal anesthesia. Skin was disinfected and 40mg of 2% Lidocaine was given subcutaneously at lumbar vertebrae 3/4 level. 25 G spinal needle was used and after dura and arachnoidea were pierced 12.5-15 mg of 0.5% Levobupivacaine was applied. Participants were then positioned in uniform lithotomy position and 9cm pillow was inserted. After sensory block, defined as the absence of pain at T10 dermatome, was induced by needle-tip test by the anaesthesiologist, the surgery was initiated. Time after subarachnoid block was T0 and sedation with midazolam or dexmedetomidine was started via continuous intravenous infusion. Midazolam was started with 0.25 mg/kg of ideal body mass, and dexmedetomidine with 0.5 ug/kg through 10 minutes. Every 10 minutes sedation level was observed with Ramsay sedation scale (RSS). Drug was titrated to achieve RSS of 4 or 5 (closed eyes and patient exhibited brisk or sluggish response to light glabellar tap or loud auditory stimulus). Independent blinded doctor was assessing RSS level, vital parameters and signs of airway obstruction every 10 minutes. Every 10 minutes systolic, diastolic and mean arterial pressure(MAP) were noticed along with heart rate, oxygen saturation by pulse oximetry(SpO2), RSS level and adverse intraoperative events: snoring as sign of airway obstruction, cough and restlessness as disturbing factors to surgeon. If peripheral oxygen fell below 90% supplemental oxygen was delivered by facemask with reservoir bag at flow of 10 L/min. End tidal carbon dioxide(CO2)was measured for detection of possible apnea. If oxygenation was still inadequate chin lift and jaw thrust maneuver were performed and oropharyngeal airway was inserted if needed. If heart rate fell below 50 bpm atropine 0.1 mg/kg was given and if systolic blood pressure fell below 100 mmHg(or MAP < 65 mmHg) ephedrine 5mg bolus was given. Total crystalloid infusion volume was noticed at the end of surgery. All measurements were performed every 10 minutes and 1 hour after surgery in urology intensive care. High risk OSA participants underwent cardiorespiratory polygraphy at Center for sleep medicine Split.

Official Title
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Comparison of Intraoperative Complications in Patients With or Without High Risk for Obstructive Sleep Apnea During Sedation With Midazolam or Dexmedetomidine Within Transurethral Resections of Bladder and Prostate

Conditions
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Anesthesia, Anesthesia Complication, Osa Syndrome, Transurethral Resection of Prostate, Sedation Complication, Intraoperative Complications, Snoring, Airway Obstruction

Intervention / Treatment
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* Procedure: Spinal anesthesia with intraoperative dexmedetomidine sedation
* Procedure: Spinal anesthesia with intraoperative midazolam sedation
* Drug: Dexmedetomidine
* Drug: Midazolam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: elective transurethral resection of bladder and prostate American Society of Anesthesiologists (ASA) physical status classification system: I, II, III Exclusion Criteria: regional anesthesia contraindications American Society of Anesthesiologists (ASA) physical status classification system: IV Atrioventricular cardiac block II and III degree Psychotic disorders Participants with tracheostomy Dementia Allergy on Dexmedetomidine or Midazolam

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: factorial randomised controlled trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: High risk OSA Dexmedetomidine<br>High risk OSA defined by STOP BANG questionnaire Intraoperative sedation during spinal anesthesia for transurethral resection of bladder and prostate | Procedure: Spinal anesthesia with intraoperative dexmedetomidine sedation<br>* Skin was disinfected and 40mg of 2% Lidocaine was given subcutaneously at lumbar vertebrae 3/4 level. 25 G spinal needle was used and after dura and arachnoidea were pierced 12.5-15 mg of 0.5% Levobupivacaine was applied.<br>Drug: Dexmedetomidine<br>* Dexmedetomidine 0.5 ug/kg during first 10 minutes after successful spinal anesthesia. Dose maintained to keep patient in moderate sedation with closed eyes and Ramsay sedation scale 4 and 5 level<br>* Other names: Dexmedetomidine sedation;|
| Active Comparator: High risk OSA Midazolam<br>High risk OSA defined by STOP BANG questionnaire Intraoperative sedation during spinal anesthesia for transurethral resection of bladder and prostate | Procedure: Spinal anesthesia with intraoperative midazolam sedation<br>* Skin was disinfected and 40mg of 2% Lidocaine was given subcutaneously at lumbar vertebrae 3/4 level. 25 G spinal needle was used and after dura and arachnoidea were pierced 12.5-15 mg of 0.5% Levobupivacaine was applied.<br>Drug: Midazolam<br>* Midazolam 0.25 mg/kg ideal body weight during first 10 minutes after successful spinal anesthesia. Dose maintained to keep patient in moderate sedation with closed eyes and Ramsay sedation scale 4 and 5 level<br>* Other names: Midazolam sedation;|
| Active Comparator: Low&Medium OSA Dexmedetomidine<br>Low&Medium OSA defined by STOP BANG questionnaire Intraoperative sedation during spinal anesthesia for transurethral resection of bladder and prostate | Procedure: Spinal anesthesia with intraoperative dexmedetomidine sedation<br>* Skin was disinfected and 40mg of 2% Lidocaine was given subcutaneously at lumbar vertebrae 3/4 level. 25 G spinal needle was used and after dura and arachnoidea were pierced 12.5-15 mg of 0.5% Levobupivacaine was applied.<br>Drug: Dexmedetomidine<br>* Dexmedetomidine 0.5 ug/kg during first 10 minutes after successful spinal anesthesia. Dose maintained to keep patient in moderate sedation with closed eyes and Ramsay sedation scale 4 and 5 level<br>* Other names: Dexmedetomidine sedation;|
| Active Comparator: Low&Medium OSA Midazolam<br>Low&Medium OSA defined by STOP BANG questionnaire Intraoperative sedation during spinal anesthesia for transurethral resection of bladder and prostate | Procedure: Spinal anesthesia with intraoperative midazolam sedation<br>* Skin was disinfected and 40mg of 2% Lidocaine was given subcutaneously at lumbar vertebrae 3/4 level. 25 G spinal needle was used and after dura and arachnoidea were pierced 12.5-15 mg of 0.5% Levobupivacaine was applied.<br>Drug: Midazolam<br>* Midazolam 0.25 mg/kg ideal body weight during first 10 minutes after successful spinal anesthesia. Dose maintained to keep patient in moderate sedation with closed eyes and Ramsay sedation scale 4 and 5 level<br>* Other names: Midazolam sedation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Airway complications | Snoring detection, SpO2 and patient respiration monitoring, If SpO2 fell below 90% supplemental oxygen was delivered by facemask with reservoir bag at flow of 10 L/min. If oxygenation was still inadequate chin lift and jaw thrust maneuver were performed and oropharyngeal airway was inserted. | During surgery | 
| Coughing and restlessness | Participants have to be relaxed and calm during surgery and sedation. Theirs coughing and restlessness result in movement that is disturbing to surgeon because they could puncture bladder/prostate with resectoscope and cause perforation. So when surgeon complains about participants movement due to theirs coughing and restlessness investigators check that on list. | During surgery | 
| Cardiorespiratory polygraphy | OSA classification with apnea hypopnea index(AHI) for High risk OSA participants | up to 30 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arterial blood pressure | Systolic, diastolic and mean arterial blood pressure changes, Ephedrine use if systolic blood pressure < 100 mmHg or MAP<65 mmHg | During surgery | 
| Symptomless Multi-Variable Apnea Prediction(sMVAP) index | OSA risk calculated by gender, age and BMI | up to 30 weeks | 
| Medications | Medications that participant use regularly | During surgery | 
| Heart rate | Atropine 0.1 mg/kg use if pulse<50 | During surgery | 
| Cigarette smoking | Participant is active cigarette smoker or nonsmoker | During surgery | 
| ASA status | Participant ASA status | During surgery | 
| Crystalloid infusion | Volume of crystalloid infusion at the end of surgery | During surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dexmedetomidine, Midazolam, STOP BANG questionnaire, Intraoperative complications, Spinal anesthesia, Cardiorespiratory polygraphy, sMVAP index, Sedation