Prospero propofol registration.pdf

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Participants/ population
The target population consists of paediatric patients (age ranging from 28 days to 19 years) receiving sedation using
propofol for more than 60 minutes in a hospital (intensive care unit, operating room, emergency room, or any other
location within the hospital) or other medical setting (for example dentist offices). The indication for sedation will not
be a restriction at this time; instead,
it will be the subject of a subgroup analysis. This is a review of adverse events of propofol infusion in paediatric
patients, so it has broad inclusion criteria (any children receiving propofol infusion for sedation).

Intervention(s), exposure(s)
The intervention being studied is the use of propofol as an anaesthetic drug given by continuous infusion. It is not
clear the length of infusion necessary to cause PRIS. The case reports are usually associated with prolonged use
(more than 48 hours) and in high doses (more than 4 mg/kg/hour). We will include patients receiving infusions lasting
60 minutes or longer, as an arbitrary number.
Further, we will exclude studies in which propofol bolus or infusion was given in more than one study arm, in order
to have a propofol free comparison group and to limit the possible risk factor to one single arm. As propofol does not
provide analgesia, the group receiving propofol can also receive other sedative, analgesic drugs concomitantly.

Comparator(s)/ control
The comparison group, will be any sedative or analgesic agent different from propofol, alone or in combination.

Primary outcomes
The primary outcome is the report of PRIS or any other serious adverse events resulting in cardiac arrest (with return
to spontaneous circulation or use of extra-corporeal life support) or death associated with propofol use as a
continuous infusion in paediatric patients. The follow-up time to measure the primary outcome for this study will be
the development of the outcome of interest (PRIS or cardiac arrest) or time of hospital discharge for patients who did
not develop the primary outcome.
The primary outcomes will be defined as the following:
Cardiac arrest, a reduction of cardiac output requiring any of the following: chest compressions; defibrillation,
epinephrine boluses or cardiac mechanical support (extra-corporeal life support (ECLS); or ventricular assist device
Propofol infusion syndrome (PRIS) will be defined as metabolic acidosis, arterial pH 7.3 along with a serum
bicarbonate 18 mg/dL; plus the presence of any signs in any the below categories (adapted from Roberts 2009):
1. rhabdomyolysis (the breakdown of muscle fibres resulting in the release of muscle fibre contents (myoglobin) into
the bloodstream), defined as creatine phosphokinase (CPK)  10,000 IU/L or positive serum or urine myoglobin test
or positive urinary casts for haemoglobin;
2. hypotension (initiation of a vasopressor agent or increase of  20% from baseline;
3. hepatic transaminitis (increase in aspartate aminotransferase or alanine aminotransferase, or both, 3 times above
4. hypertriglyceridaemia (serum triglyceride concentration 400 mg/dL);
5. hypoxia (partial pressure of arterial oxygen  60 mm Hg);
6. hyperthermia (temperature  38.3 °C);
7. cardiac dysfunction that includes asystole, pulseless electrical activity, ventricular fibrillation, sustained
ventriculartachycardia of 30 seconds or longer, myocardial failure (ejection fraction 40%), or bradycardia (heart rate
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