Clinical Trial – High-flow Oxygen for Vaso-occlusive Pain Crisis

Sickle cell disease (SCD) is characterized by recurrent vaso-occlusive pain crisis (VOC),
which may evolve to acute chest syndrome (ACS), the most common cause of death among adult
patients with SCD. Currently, there is no safe and effective treatment to abort VOC or
prevent secondary ACS. Management of VOC mostly involve a symptomatic approach including
hydration, analgesics, transfusion, and incentive spirometry, which was investigated in a
very limited number of patients (<30). The polymerisation of HbS is one major feature in the pathogenesis of vaso-occlusion. Among factors determining the rate and extent of HbS polymer formation, the hypoxic stimulus is one of the most potent and readily alterable. Current guidelines recommend oxygen therapy in patients with VOC in order to maintain a target oxygen saturation of 95%. Low-flow nasal oxygen (LFNO) is routinely used to achieve this normoxia approach, particularly in patients at risk of secondary ACS because they may experience acute desaturation. In contrast, various case series suggest a potential beneficial role of intensified oxygen therapy targeting hyperoxia for the management of VOC, particularly with the use of hyperbaric oxygen, but the latter is difficult to implement in routine clinical practice. A recent high-flow nasal oxygen (HFNO) technology allows the delivery of humidified gas at high fraction of inspired oxygen (FiO2) through nasal cannula. The FiO2 can be adjusted up to 100% (allowing hyperoxia that may reverse sickling) and the flow can be increased up to 60 L/min (which generates positive airway pressure and dead space flushing, that may prevent evolution of VOC towards ACS by alleviating atelectasis and opioid-induced hypercapnia). In patients with acute respiratory failure, HFNO has been shown to improve patient's comfort, oxygenation, and survival as compared to standard oxygen or non-invasive ventilation. The aim of the present study is to test the efficacy and safety of HFNO for the management of VOC and prevention of secondary ACS. The investigators will use a multi-arm multi-stage (MAMS) design to achieve these goals. HFNO will be delivered through AIRVO 2 (Fisher and Paykel Healthcare, New Zealand), a device that incorporates a turbine allowing its use in hospital wards.

Clinical Trial – Effect of Intrathecal Morphine on Chronic Pain After Elective Caesarean Section

The incidence of chronic post-surgical pain (CPSP) after caesarean section (CS) is reported
to be as high as 18%, reflecting it to be a significant clinical problem. Studies related to
prevention of progression of acute post-CS pain to its chronicity are sparse. Current
guidelines on post-CS analgesia recommend the use of intrathecal (IT) opioids to spinal
anaesthesia for improved post-CS pain relief. Despite its frequent use, studies related to
the IT morphine use and its association with post-CS chronic pain are lacking.

A recent prospective observation study revealed a significant reduction in persistent pain
after CS when IT morphine was used as an adjuvant to spinal anaesthesia. However, there is no
any randomized controlled trial (RCT) that has explored this association to date. We
hypothesized that spinal morphine would reduce the incidence of persistent pain after CS.