Time out
I am taking a time out because I want to go back to 2014. At that time there were no mandatory guidelines regarding the administration of procedural sedation in cosmetic practice in Hong Kong. Because of the call to the emergency services from the clinic the fatal event was flagged up to the police. An investigation was begun with the first action being sealing the scene of the potential crime to allow for documentation and processing. There was a fundamental flaw in this initial processing that caused considerable confusion many years later. Indeed, it was not until during the trial that the lack of precision in the documentation of the crime scene was revealed. Photographs are used to document such aspects as syringes, drug vials, etc to record what drugs were used during the procedure. In the documentation given to the medical experts was a picture of four empty vials of propofol. These had been removed from the sharps bin where they had been discarded. There were empty vials and used syringes from previous procedures as the sharps bin is not emptied after each procedure. It appears that there was some breakdown in communication so that the entire contents of the sharps bin were not recorded and the four empty vials of propofol which were in the photographs were not the only empty vials of propofol in the bin. It is for this reason that the comments on the drug dosages were misleading. The vials were 20mls each giving a total of 80mls. The concentration of propofol was 10mg/ml so the working assumption was that the maximum dose of propofol was 800mg. This was given over three hours to a patient weighing 113.5 kg. This gives a rate of 2.3 mg/kg/hour. This is well within the limits of infusion recommended for maintaining procedural sedation in an adult (1.5-4.5mg propofol/kg bodyweight/hour). This is a very safe dosage, but it was wrong. As the Judge comments, credit must be given to Dr Mainland for her very patient review of the CCTV data which indicated a much larger dosage was given.
The following is an extract from the Judge’s Reason for Sentence:
Para 18 – 20
18. After Lee was infused with the combination of sedative drugs at the start of the procedure she was deeply sedated and unconscious. It transpired only at trial after the careful viewing of the CCTV recordings by the prosecution expert Dr Mainland an anaethesiologist, that Lee was infused with seven separate syringes of propofol. The first syringe started at about 1134 hours and the seventh and last syringe at about 1409 hours. A total of 14 ampoules which amounted to 2,800 mg of propofol was administered to Lee.
19. This belated uncovering emerged as the prosecution only synchronized the two CCTV camera recordings after the trial had commenced. This occasioned the viewing of both camera recording in the operation room together as complete picture as opposed to only a partial viewing of one camera recording each time.
20. Communication and response was lost with Lee almost from the beginning of the operation save for a short period between the 5th and 6th syringe of propofol when Lee came out of deep sedation and said the words “painful, painful, painful and don’t press on my hand” at about 1348 hours. Dr Mainland explained that Lee came out of deep sedation because there was a break of about 6½ minutes between the 5th and 6th syringe of propofol and as a result Lee’s sedation became lighter. However shortly thereafter Lee was infused with the 7th syringe of propofol and was under deep sedation again.
[This timeline does not make sense as the patient was responding to pain at 13:48 and the last syringe was commenced at 14:09 (according to the Judge). With each syringe in the pump holding two vials of propofol (20ml each) that gives a volume of 40ml total. 40ml at 90ml per hour gives a time of 26 minutes per syringe in the pump. The Judge is confused and rightly so. This is a complex matter and I do not think we can blame the Judiciary for not understanding what is going on. What we can blame them for is the arrogance that they display in pretending that they do.]
What does this all mean? What are the recommended dosages for propofol when used for general anaesthesia and for procedural sedation?
Recommendations for dosage for an adult patient: (source: https://www.medicines.org.uk)
For general anaesthesia:
Induction: ~1.5 to 2.5 mg propofol/kg body weight (bolus)
Maintenance: ~4 to 12 mg propofol/kg body weight/h (infusion)
For procedural sedation:
Induction: ~0.5 to 1mg propofol/kg body weight over 1 to 5 minutes for onset of sedation
Maintenance: ~1.5 to 4.5 mg propofol/kg body weight/h (infusion)
Ms Lee had a bolus of 60mg of propofol (i.e. 0.53mg/kg body weight). Then she received an infusion to maintain a deep level of consciousness. This dose was 8.2mg/kg/hr. Using the infusion pump the rate was set at 90ml/hour.
Why this rate? This comes back to how do doctors learn their prescribing habits. According to a personal communication from Dr Kwan, the Korean Plastic Surgeon whom she visited told her a rough rule of thumb was to use an infusion rate of 1ml/kg/hour and reduce the rate if there were any concerns. Thus, Dr Kwan kept within the “guidelines” that she had been given and that she had seen to be safe and effective in Korea. Is that a crime?!
This never came out in the trial as no defence was mounted. It was bizarre and ludicrous. This underlines why the adversarial system is so inadequate when establishing the truth in these complex medical situations. In an inquisitorial system a key question would have been to find out why a doctor did what they did.
Propofol is a fascinating drug and it is not just in the purview of anaesthetists to take an interest in the clinical neuroscience aspects of its use. These two YouTube videos are very insightful and take a basic science approach to understanding how propofol affects the brain. It creates oscillations that interfere with normal communications in this highly sophisticated organ. These oscillations can be measured and can reflect the degree of unconsciousness in a patient under anaesthesia or sedation.
https://youtu.be/lss9V79zn5Q
https://youtu.be/fkGcmHRNMT4
It would appear intuitively obvious that one of the safest ways to use propofol is to do so in the context of brain monitoring. That is the basis of the work of Dr Barry Friedberg who is the Pioneer of Brain Monitored Propofol Ketamine aka Goldilocks anesthesia. This is not new, and Dr Friedberg has been working on this since 1993. He has written more about procedural sedation in Cosmetic Surgery than any other single author and has published the definitive text: Friedberg, B. (Ed.). (2007). Anesthesia in cosmetic surgery. Cambridge University Press.
Finally for this blog when talking about propofol a number of terms are relevant:
Distribution half-life: the time required for plasma concentration of a drug to decrease by 50% (for propofol this is measured in minutes).
Elimination half-life: the time it takes for the total amount in the body to be reduced by 50%. (for propofol this is measured in hours).
Context sensitive half-life: the time taken for blood plasma concentration of a drug to decline by one half after an infusion designed to maintain a steady state has been stopped. The "context" is the duration of infusion (for propofol this is time and not dose dependent and there is little difference between a two-hour infusion and a three-hour infusion).
There is a good discussion of context sensitive half-life available in the free online source
https://derangedphysiology.com/main/
cicm-primary-exam/required-reading/pharmacokinetics/
Chapter%20323/context-sensitive-half-time
What does this all mean? I am not sure at the moment. What I am sure about is that Hong Kong needs some consensus guidelines for procedural sedation and at this time they do not have them. Guidelines without consensus have no basis or place in a Court of Law. Consensus guidelines are based on facts, not opinions.
