Evaluation of a New Protocol for Adult Procedural Sedation With Ketamine-propofol in a 1 on 4 Ratio

Study Overview
=================
Brief Summary
-----------------
Procedural sedation is the monitored use of sedatives and/or analgesics in a patient who must endure a short painful or frightening procedure, bringing the patient into a sedative state while retaining his spontaneous breathing and respiratory reflexes. Examples of these procedures are cardioversion, repositioning of a shoulder luxation or incision of a skin abscess, and these are frequently performed at the emergency ward. An easy and unambiguous protocol for procedural sedation was composed at the emergency department of the University Hospital of Ghent applicable for nearly all patients and procedures. This protocol included recommendations for necessary monitoring such as continuous electrocardiogram, intermittent blood pressure measurements, oxygen saturation and capnography, as well as safety precautions for standby medications or medical devices for hemodynamic and airway control. As sedative drug a mixture of ketamine and propofol (ketofol) in a 1 on 4 ratio was selected based on the available literature. Both ketamine and propofol are known to neutralise each other's undesirable effects and ketamine adds an analgesic quality. Ketofol has proven effective and safe in studies and is non-inferior to propofol. Though it is most often used in a 1 on 1 ratio, both pharmacological and clinical studies favour a 1 on 4 ratio. An adult patient presenting at the investigating hospital in need of procedural sedation, who agreed the informed consent for procedural sedation was treated according to this protocol. Patients with an American Society of Anesthesiologist physical status classification system status of III or more, with an anticipated difficult airway or intoxicated patients were discussed with the anaesthesiology department to decide the feasibility of sedation in the emergency ward setting. Pregnant patients were excluded. Associated to this newly implemented protocol, an observational prospective study was associated to verify the safety and effectivity, and to score the physicians satisfaction. A separate informed consent was obtained for participation in the study to permit inclusion of patient and procedural data into a registry. Data was registered by the physician responsible for the sedation in a questionnaire. The investigators hypothesized the protocol with ketofol in a 1 on 4 ratio would be safe and effective and would serve to facilitate procedural sedation by emergency physicians.

Detailed Description
-----------------
Procedural sedation is the monitored use of sedatives and/or analgesics in a patient who must endure a short painful or frightening procedure, bringing the patient into a sedative state while retaining his spontaneous breathing and respiratory reflexes. Examples of these procedures are cardioversion, repositioning of a shoulder luxation or incision of a skin abscess, and these are frequently performed at the emergency ward. An easy and unambiguous protocol for procedural sedation was composed at the emergency department of the University Hospital of Ghent applicable for nearly all patients and procedures. This protocol included recommendations for necessary monitoring such as continuous electrocardiogram, intermittent blood pressure measurements, oxygen saturation and capnography, as well as safety precautions for standby medications or medical devices for hemodynamic and airway control. As sedative drug a mixture of ketamine and propofol (ketofol) in a 1 on 4 ratio was selected based on the available literature. Both ketamine and propofol are known to neutralise each other's undesirable effects and ketamine adds an analgesic quality. Ketofol has proven effective and safe in studies and is non-inferior to propofol. Though it is most often used in a 1 on 1 ratio, both pharmacological and clinical studies favour a 1 on 4 ratio. According to the protocol ketofol 1 on 4 was prepared by mixing 1ml of ketamine (50mg) and 20ml of propofol (200mg) in a single syringe and administrated as a loading dose of 1ml/10kg, followed by a stepwise titration in aliquots of 0,5ml/10kg. Above 65 years the loading dose was halved. An adult patient presenting at the investigating hospital in need of procedural sedation, who agreed the informed consent for procedural sedation was treated according to this protocol. Patients with an American Society of Anesthesiologist physical status classification system status of III or more, with an anticipated difficult airway or intoxicated patients were discussed with the anaesthesiology department to decide the feasibility of sedation in the emergency ward setting. Pregnant patients were excluded. Associated to this newly implemented protocol, an observational prospective study was associated to verify the safety and effectivity, and to score the physicians satisfaction. A separate informed consent was obtained for participation in the study to permit inclusion of patient and procedural data into a registry. Data was registered by the physician responsible for the sedation in a questionnaire. The investigators hypothesized the protocol with ketofol in a 1 on 4 ratio would be safe and effective and would serve to facilitate procedural sedation by emergency physicians.

Official Title
-----------------
Prospective Observational Evaluation of a New Protocol for Adult Procedural Sedation With Ketamine-propofol in a 1 on 4 Ratio at the Emergency Department of a Tertiary Hospital

Conditions
-----------------
Procedural Sedation and Analgesia

Intervention / Treatment
-----------------
* Drug: Procedural sedation with ketofol in a 1 on 4 ratio


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All adult patients presenting to the university hospital of Ghent and in need of procedural sedation as determined by the treating physician, who underwent procedural sedation by the standard protocol using ketofol in a 1 on 4 ratio. Exclusion Criteria: pregnant patient procedural sedation not performed at the emergency department

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| participants undergoing procedural sedation<br>The study gathered observational data about participants who underwent procedural sedation according to the new standard protocol with ketofol in a 1 on 4 concentration. The participant was observed for complications or cardiorespiratory interventions by the sedating physician until he was fully awake. Thirty minutes after the awakening, the participant was questioned for his remembrance and perception of the sedation and procedure. He was observed for complications until discharge | Drug: Procedural sedation with ketofol in a 1 on 4 ratio<br>* The participant was brought to a zone where advanced life support could be optimally administered and where all necessary drugs and materials for treatment of complications are present. Oxygen saturation, continuous electrocardiogram, intermittent blood pressure measurement (every 2 minutes) and capnography were applied. A 20 gauge intravenous line was inserted. The participant was placed in semi-recumbent position and was given oxygen for at least 3 minutes through a non-rebreather mask unless contra-indications applied. Ketofol 1 on 4 was prepared by mixing 1ml of ketamine (50mg) and 20ml of propofol (200mg) in a single syringe. It was administrated as a loading dose of 1ml/10kg, corresponding to 0,952mg/kg propofol and 0,238mg/kg ketamine, and followed by titration in aliquots of 0,5ml/10kg every 1 to 2 minutes until desired depth of sedation was achieved, and then every 3-5 minutes to retain the desired depth of sedation. The loading dose was halved if above 65 years.<br>* Other names: Ketofol;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory complication or intervention | Complication: desaturation (< 92%), apnea (absent end-tidal CO2 for > 15s and no breathing movements), hypoventilation (respiratory frequency < 8 /minute), airway obstruction (absent end-tidal CO2 for > 15s and breathing movements), laryngospasm (partial or complete airway obstruction, not responding to airway repositioning or introduction of naso- or oropharyngeal cannula), aspiration due to vomiting Intervention: airway repositioning (head tilt or chin lift), pain stimulus for breathing stimulation, introduction of naso- or oropharyngeal cannula, positive pressure ventilation, introduction of laryngeal mask or endotracheal tube | From start of sedation, until half an hour after participant woke up from sedation ( participant fully communicative and obedient for commands). On average a total monitoring time of 40 minutes. | 
| Hemodynamic complication or intervention | Complication: hypotension (systolic blood pressure less than 90mmHg, or drop of 10% of systolic blood pressure ) Intervention: fluid bolus given, use of inotropes | From start of sedation, until half an hour after participant woke up from sedation ( participant fully communicative and obedient for commands). On average a total monitoring time of 40 minutes. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Success of procedure | sedation adequate for performing procedure (yes/no) | From start of sedation, until participant woke up from sedation ( participant fully communicative and obedient for commands). Assessment was made at time of awakening | 
| Amnesia | amnesia of the procedure by the patient (yes/no) | Assessed 30 minutes after awakening ( participant fully communicative and obedient for commands) and addressing the moment of performance of the procedure during sedated state | 
| Agitation or hallucination | Agitation during or after sedation (yes/no) Hallucination during or after sedation (yes/no) If hallucination: Pleasant / neutral / unpleasant | From start of sedation, until half an hour after participant woke up from sedation ( participant fully communicative and obedient for commands). On average a total monitoring time of 40 minutes. | 
| Duration of sedation | Time from start of sedation till completely awake, expressed in minutes | Start of sedation until awakening ( participant fully communicative and obedient for commands) | 
| Satisfaction sedating physician | - satisfaction of the sedation with the current protocol, score on a five point Likert scale (++ / + / + - / - / - - , meaning very satisfied / satisfied / neither satisfied nor dissatisfied / dissatisfied / very dissatisfied ) | Assessed 30 minutes after awakening ( participant fully communicative and obedient for commands), concerning the period from start of sedation until 30 minutes after awakening | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ketofol, propofol, ketamine, emergency department