Background: Sickle cell disease (SCD) is one of the most common genetic diseases in the
world, affecting approximately 310,000 births each year and causing >100,000 deaths.
Vaso-occlusive crisis (VOC) is the most frequent complication of SCD, leading to bone pain,
thoracic pain and/or abdominal spasms and is the main cause of death in patients with SCD. It
is linked to sickling which is often triggered by internal and external environmental
conditions such as acidosis, cold, dehydration, hyperthermia, infection and especially
hypoxia. Sickling is initially reversible if local oxygenation supply and conditions are
improved.
Rationale: The use of hyperbaric oxygen therapy (HBOT) should enable the patient's tissues to
receive the extra oxygen necessary by increasing the amount of dissolved O2 in blood which in
turn would limit sickling. A pilot study of 9 patients showed the potential positive effects
of HBOT on VOC induced pain. International guidelines indicate that SCD-induced VOC is one of
the potential indications for HBOT, even though the evidence available is weak.
Aim and objectives: To demonstrate the analgesic effect of HBOT for VOC and to analyse the
procedure's safety, impact on the biological markers of SCD-induced VOC, progression of SCD
and cost-effectiveness.
Methodology: This study will be a multicentric, double-blind, randomised controlled trial.
Any patient presenting at one of the participating centres' Emergency Departments (EDs) with
VOC is eligible to be evaluated, included and randomized. Inclusion criteria: Patients aged 8
years or over with a major SCD, having a VOC non-responsive to level 2 analgesics (WHO
classification), with or without Acute Chest Syndrome (ACS). Exclusion criteria: Pregnancy,
indication for artificial ventilation, proven contraindication for HBO, blood velocity > 200
cm/sec previously measured with transcranial Doppler, previous history of stroke, patient
requiring more than 2 l/min of normobaric oxygen in order to achieve an SpO2 (peripheral
oxygen saturation) ≥ 92%. Patients with exclusion criteria, although precluded from the
randomisation process, will however be eligible to undergo the HBOT intervention and become
part of the cohort. Measurements and procedures: In all cases, included patients will receive
usual care for VOC, including hydration, analgesics (patient-controlled analgesia with
morphine), normobaric oxygen therapy and where medically indicated, antibiotic therapy and/or
transfusions. Within 4 to 12 hours of their initial consultation at their hospital's ED,
patients who have agreed to participate in the study will be randomised between the HBOT
intervention group (2 Atmosphere Absolute pressure [ATA], 95 min, FIO2 = 1) and the placebo
group (1.3 ATA, 95 min, FIO2 = 0.21). Patients will undergo a first session in the hyperbaric
chamber and then return to their ward. The second (and third) session (for both groups) will
systematically take place within 24 h (max. 36 h) of the first session. If the visual
analogue scale (VAS) pain score is ≤ 2 without the use of level 3 analgesics at the standard
dosage, subsequent sessions will be cancelled. Difference in the visual analogue scale (VAS)
pain score before and after HBOT and other outcomes will be compared between the intervention
and placebo groups. A superiority of HBOT compared placebo group in VOC should be
demonstrated, with decrease of pain, length of stay and cost.
Expected results and their impact: Expected benefits of HBOT are the reduction of: pain
experienced, duration of the crisis, number of transfusions required, the number of morphine
doses, reduction of length of stay and reduction in the frequency of ACSs and VOCs.
