Sickle-related pain

• Vaso-occlusion can result in crises characterized by acute pain, which is the most common cause of hospitalization for SCD (150). People typically present with severe joint, back, chest or extremity pain. Vaso-occlusive crises may be triggered by infection, temperature extremes, dehydration, hypoxia, acidosis, or may be spontaneous. During pregnancy, sickle-cell crises are the most common maternal complication, occurring in 55.8% of SCD pregnancies (151, 152).
• The WHO [African Region] SICKLE Package of Interventions for Sickle Cell Disease Management highlights the importance of managing sickle-related pain within 30 minutes of presentation to care (23). Vasoocclusive episodes are often an inciting event for acute chest syndrome, which is a leading cause of mortality in SCD (23). Pain medications in the general pregnant population
• Paracetamol: Paracetamol is considered safe for use throughout pregnancy (153).
• NSAIDs: The use of NSAIDs during the first trimester is associated with an increased risk of congenital anomalies (154). After 30 weeks of gestation, NSAIDs can lead to premature closure of the ductus arteriosus and neonatal pulmonary hypertension, and reduce fetal renal blood flow and urine production, leading to a reduced amniotic fluid volume (153).
• Opioids: For the woman, long-term opioid use during pregnancy can lead to maternal dependence (153). For the neonate, opioid use in pregnancy is associated with low birth weight, preterm birth, stillbirth and maternal death. Neonatal withdrawal syndrome has also been described in neonates with prolonged exposure in utero. The limited data on the safety of opioid analgesics during the first 30 weeks of pregnancy do not indicate an increased risk of fetal toxicity (153). Opioid use, especially around the time of delivery, may lead to neonatal respiratory depression and/or neonatal withdrawal symptoms (153). It is therefore prudent to report maternal opioid use in pregnancy to the neonatal care team. Pain medications in people with SCD
• The pain of mild sickle-cell crises is generally managed with paracetamol, a NSAID, codeine phosphate, or dihydrocodeine tartrate (155). Severe crises may require the use of morphine or diamorphine hydrochloride; concomitant use of a NSAID may potentiate analgesia and allow lower doses of the opioid to be used (155). Pethidine hydrochloride is generally avoided if possible because accumulation of a neurotoxic metabolite can precipitate seizures; the relatively short half-life of pethidine hydrochloride necessitates frequent injections (155). Considerations in people with SCD
• Guidance from the WHO African Region is that pain management includes both symptom management and prevention, including use of disease-modifying agents; individualized and tailored treatment; management of pain across different levels of the health system; and response to acute pain crisis that includes rapid assessment of recent analgesic use, rapid administration of therapy, and reassessment and readministration if pain persists (23).
• NSAIDs: NSAIDs may be important adjuvant analgesic agents in the management of SCD pain in pregnancy. Concomitant use of a NSAID may potentiate analgesia and allow lower doses of an opioid to be used (155). NSAIDs may be used at the lowest effective dose for the time period needed when other medications are insufficient to control pain (153). The GDG noted, however, that women with SCD may have comorbid kidney disease/renal dysfunction. Use of NSAIDs in individuals with chronic renal disorders is considered contraindicated due to the risks of nephrotoxicity (156).
• Opioids: The GDG noted that the WHO [African Region] sickle package of interventions for sickle cell disease management suggests that opioids be made available in centres with physicians.