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When you thought you had heard everything about Propofol with recent media cover over the unfortunate event involving a pop star, a paper from Iran suggest that there would be a role for its use in refractory migraines!
What was this paper about?
This study was set to evaluate the role and efficiency of intravenous Propofol in patients presenting to the ED with refractory migraines defined as headaches not resolved with usual analgesics (NSAIDs, triptans, dexamethasone, opioids etc.). It is believed its pharmacological effects are related to the active molecule binding to the gamma-aminobutyric acid (GABA) receptors that are downregulated in migraines.
Interesting concept indeed in theory but can we draw hard line clinical conclusions from a case series considering that they are at the bottom of the pyramid of evidence?
The authors recruited eight patients presenting to ED with refractory migraine headaches as defined above. A small number of patients indeed making this trial open to systematic errors (bias) and random errors (chance).
The crucial recruitment process is not clearly defined either: one could not work out if these patients had a formal diagnosis of migraine (and that is why they had taken triptans and opioids prior to ED presentation) or if they were diagnosed at point of presentation using the International Headache Society (IHS) criteria as suggested by the paper. A stringent selection of recruited patients is needed indeed in any trail as this will affect the generalisability of your findings and the recommended steps of identification of patients, assessment of eligibility, consent and recruitment/randomisation information is clearly missing here.
A Visual Analogue Scale (VAS) was recorded at the point of recruitment and after treatment that consisted of boluses of IV Propofol to alleviate the headache. If you are not familiar with the VAS then you can have a look here. It is a validated tool to record pain in subjects but such an assessment is highly subjective, when looking at change within individuals, and are of less value for comparing across a group of individuals at one time point.
They have been also valid point raised during the Twitter JC session about its reliability in acute severe pain and during the administration of a sedative.
Furthermore the authors did not define what they considered therapeutic effect and it is difficult therefore to interpret their results.
The authors followed up all patients by phone for 72 h after discharge from the ED. Of eight patients being followed up during this time period, six were found to remain without symptoms. One case however experienced a headache at follow-up and another one also reported recurrence 36 h later. Both were relieved by NSAIDs.
The authors concluded after expanding pharmacology in the discussion, that Propofol is an effective, rapid-acting, safe drug and with few side effects for relieving refractory migraine headaches.
Take home message:
Can we draw conclusions from a simply descriptive study involving small numbers, with a dubious recruitment process and potentially unreliable measurements? Let us not be completely negative about this theoretically interesting concept as any large multi-centre trial usually starts with a pilot study like this one!
A dose finding study probably needs to be established to establish the efficacy of Propofol in this clinical context and a randomised controlled trial or a cross-over trial is probably needed before hard conclusions can be drawn for clinical practice…