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

Procedural Sedation and Analgesia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04028141
• Other study ID #: B670201834755
• Status: Completed
• Start date: February 1, 2018
• Est. completion date: March 31, 2019

Study information

• Verified date: July 2019
• Source: University Hospital, Ghent
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: March 31, 2019
• Est. primary completion date: March 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Procedural Sedation and Analgesia

Intervention

Drug:
• Procedural sedation with ketofol in a 1 on 4 ratio
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.

Locations

Country	Name	City	State
Belgium	University Hospital of Ghent - Emergency Department	Ghent	East-Flanders

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Ghent

Country where clinical trial is conducted

Belgium, 

References & Publications (6)

Andolfatto G, Abu-Laban RB, Zed PJ, Staniforth SM, Stackhouse S, Moadebi S, Willman E. Ketamine-propofol combination (ketofol) versus propofol alone for emergency department procedural sedation and analgesia: a randomized double-blind trial. Ann Emerg Med. 2012 Jun;59(6):504-12.e1-2. doi: 10.1016/j.annemergmed.2012.01.017. Epub 2012 Mar 7. — View Citation

Ferguson I, Bell A, Treston G, New L, Ding M, Holdgate A. Propofol or Ketofol for Procedural Sedation and Analgesia in Emergency Medicine-The POKER Study: A Randomized Double-Blind Clinical Trial. Ann Emerg Med. 2016 Nov;68(5):574-582.e1. doi: 10.1016/j.annemergmed.2016.05.024. Epub 2016 Jul 22. — View Citation

Godwin SA, Caro DA, Wolf SJ, Jagoda AS, Charles R, Marett BE, Moore J; American College of Emergency Physicians. Clinical policy: procedural sedation and analgesia in the emergency department. Ann Emerg Med. 2005 Feb;45(2):177-96. Review. — View Citation

Jalili M, Bahreini M, Doosti-Irani A, Masoomi R, Arbab M, Mirfazaelian H. Ketamine-propofol combination (ketofol) vs propofol for procedural sedation and analgesia: systematic review and meta-analysis. Am J Emerg Med. 2016 Mar;34(3):558-69. doi: 10.1016/j.ajem.2015.12.074. Epub 2015 Dec 29. Review. — View Citation

Miner JR, Moore JC, Austad EJ, Plummer D, Hubbard L, Gray RO. Randomized, double-blinded, clinical trial of propofol, 1:1 propofol/ketamine, and 4:1 propofol/ketamine for deep procedural sedation in the emergency department. Ann Emerg Med. 2015 May;65(5):479-488.e2. doi: 10.1016/j.annemergmed.2014.08.046. Epub 2014 Oct 16. — View Citation

Yan JW, McLeod SL, Iansavitchene A. Ketamine-Propofol Versus Propofol Alone for Procedural Sedation in the Emergency Department: A Systematic Review and Meta-analysis. Acad Emerg Med. 2015 Sep;22(9):1003-13. doi: 10.1111/acem.12737. Epub 2015 Aug 20. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	American Society of Anesthesiologist physical status classification status participant	American Society of Anesthesiologist physical status classification status I, II, III of IV	start of procedure
Other	Age of participant	Age of participant in years	start of procedure
Other	Type of procedure	Reduction of luxation or fracture ( shoulder, ankle/foot, hip, elbow, other … (possibility to fill in)); Abscess incision; Cardioversion; Chest drain placement; Other: … (possibility to fill in)	start of procedure
Primary	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.
Primary	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	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
Secondary	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
Secondary	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.
Secondary	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)
Secondary	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