Ketamine-midazolam as a Sedative Agent in Endoscopic Retrograde Cholangiopancreatography.

Study Overview
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Brief Summary
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Does Ketamine-Midazolam have a better efficacy and safety profile compared to Midazolam - Pethidine in Endoscopic Retrograde Cholangiopancreatography (ERCP)?

Detailed Description
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Ketamine- Midazolom is more efficacious in producing desired sedative state and have a better safety profile as a sedative agent in ERCP compared to Midazolam- Pethidine. The usage of sedative agent in ERCP depends on surgeon's preferences and availability of the drugs. The most commonly used sedatives in ERCP is Midazolam with pethidine. The use of Midazolam , however, is related to: 20-45% failure of sedation during ERCP Cardio-respiratory depression - apnoea: 15.4%, hypotension: 15.7%, bradycardia: 6.8% Due to the proven efficacy and safety profile of ketamine-midazolam as a sedative agent in procedural sedation, the investigators propose that the use of ketamine-midazolam as a sedative agent in ERCP is more effective and better safety profile when compared to Midazolam- Pethidine. The synergistic effect means to reduce the total dose of midazolam used.

Official Title
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Combination Use of Intravenous Ketamine-midazolam as a Sedative Agent in Endoscopic Retrograde Cholangiopancreatography ; A Randomized Control Trial

Conditions
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Cholangitis, Pancreatic Cancer, Choledocholithiasis, Choledochal Cyst

Intervention / Treatment
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* Drug: Ketamine
* Drug: Midazolam
* Drug: Pethidin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults > 18 years old which able to give valid consent Patient planned for ERCP (either emergency or elective) American Society of Anaesthesiologist (ASA) score of I-III Exclusion Criteria: Known hypersensitivity towards Ketamine or Midazolam Increased intracranial pressure, acute stroke (<3 months), intracranial haemorrhage (<3 months) Severe hypertension (BP>170/110) and tachycardia (Heart rate >110) Acute myocardial infarction, acute coronary syndrome (< 6 months) Tachyarrhythmia Pregnancy Intravenous drug user (IVDU) or substance abuse patient History of hallucination Child's Pugh class C

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Interventional Model Description: Patients will be randomized into the intervention or control group (Intervention group will receive Ketamine - Midazolam and control group will receive Midazolam- Pethidine as a sedative agent in ERCP
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine - Midazolam arm<br>Initial IV Ketamine of 0.5mg/kg with IV Midazolam 0.02mg/kg given over 1 minute. If depth of sedation not adequate, to give another bolus of IV ketamine 0.25mg/kg after 2 minutes with IV Midazolam 0.01mg/kg. If depth of sedation not adequate, to give another bolus of IV Ketamine 0.25mg/kg after 2 minutes and IV Midazolam 0.01mg/kg. Failure of sedation: inadequate sedation for the intention to treat: patient will be arranged for MAC (monitored anaesthesia care) with anaesthesia team | Drug: Ketamine<br>* Administration described in arm/ group description<br>* Other names: KETAMINE- MIDAZOLAM;Drug: Midazolam<br>* Administration described in arm/ group description<br>* Other names: KETAMINE-MIDAZOLAM;|
| Active Comparator: Midazolam - Pethidine arm<br>Initial IV Midazolam 0.05mg/kg given over 1 minute with IV Pethidine 0.7mcg/kg. If depth of sedation not If adequate, to give another bolus of IV Midazolam 0.02mg/kg after 2 minutes and IV Pethidine 0.7mcg/kg. If depth of sedation not adequate, to give another bolus of IV Midazolam 0.02mg/kg after 2 minutes. Failure of sedation: inadequate sedation for the intention to treat: patient will be arranged for MAC (monitored anaesthesia care) with anaesthesia team. | Drug: Midazolam<br>* Administration described in arm/ group description<br>* Other names: KETAMINE-MIDAZOLAM;Drug: Pethidin<br>* Administration described in arm/ group description<br>* Other names: MIDAZOLAM-PETHIDIN;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the efficacy of Ketamine- Midazolam as a sedative agent in ERCP in terms of sedation failure rate. | Sedation failure rate is defined as inability of the sedation used to adequately sedate a patient for initiation and completion of procedure using ramsay sedation scale where the scale is 1 to 6, where higher score is better. Score of 1 is determined as sedation failure. | Evaluated at specific timepoints during the procedure which are: introduction of scope, canulation of bile duct, during sphincerotomy, trawling of stones, removal of stent and removal of scope | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare pre and post procedure mean arterial pressure (MAP) | To detect if there are changes in MAP calculated from participants blood pressure readings | Measured at specific time-pointswhich are: pre-sedation, 2 minutes after initiation of sedation and 5 minutes after the procedure is completed | 
| To compare surgeon satisfaction in terms of sedation quality between both arms using a likert scale of 1 to 5 where a higher score is better | Measured using likert scale | Single point asessment at the end of the procedure | 
| To compare participant satisfaction in terms of procedure experience between both groups using likert scale of 1 to 10 where the higher score is better | Measured using likert scale | Single point asessment at 2 hours after completion of procedure | 
| To compare the number of participants that developed an adverse event that led to abandonment of procedure | Adverse event by monitoring patient vital signs including blood pressure, pulse rate, oxygen saturation and procedure will be abandoned if the parameters reach a pre-set cut-off point. Systolic blood pressure <90mmHg or >180mmHg, Pulse rate of <60/min or >150/min and oxygen saturation <95% despite supplemental oxygen therapy via nasal canula. | Evaluated at specific timepoints during the procedure which are: introduction of scope, canulation of bile duct, during sphincerotomy, trawling of stones, removal of stent and removal of scope | 
| To compare the depth of sedation | The depth of sedation is evaluated using ramsay sedation scale where the scale is 1 to 6, where higher score is better | Evaluated at specific timepoints during the procedure whch are: introduction of scope, canulation of bile duct, during sphincerotomy, trawling of stones, removal of stent and removal of scope | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ketamine, Midazolam, sedation, ERCP