Pharmacological interventions for painful sickle cell vaso‐o | Figure 1

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Pharmacological interventions for painful sickle cell vaso‐occlusive crises in adults

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Medicines for treating painful sickle cell crises in adults

Bottom line

We are uncertain which medicines provide the best pain relief for adults experiencing a painful sickle cell crisis.

Background

People with sickle cell disease have abnormally shaped red cells in their blood. Sickle cell disease is the most common inherited blood disorder around the world. It is estimated globally that 367 million to 500 million people are carriers. People with sickle cell disease have a higher chance of life‐threatening complications, such as infection, severe chest pain and stroke in early life, and kidney or liver damage in adulthood.

A pain crisis is the most common problem of sickle cell disease and can require several treatments at once, usually in an emergency situation. The first priority is to control the pain, using medicines (such as opioids, non‐steroidal anti‐inflammatories, paracetamol, and blood thinners) or relaxation, hypnosis, heat, ice, or acupuncture.

Study characteristics

In September 2019, we searched for clinical trials that used medicines in any setting to treat painful sickle cell crises. We found nine trials, with 594 adults (aged 17 to 42 years) who had sickle cell disease, experiencing a combined total of 638 painful episodes.

Key results

The studies looked at different comparisons of the medicines butorphanol, cetiedil, fentanyl, ketoprofen, ketorolac, metoclopramide, morphine, paracetamol, placebo, tinzaparin, and tramadol. Only three studies compared the same two drugs (non‐steroidal anti‐inflammatory drugs such as ibuprofen, aspirin, or naproxen, with a placebo (pretend treatment)) and we had very limited data to be able to investigate the effects on pain scores from these medicines.

Side effects were rare and were generally mild.

Quality of the evidence

We rated the quality of the evidence from studies using four levels: very low, low, moderate, or high. Very low‐quality evidence means that we are very uncertain about the results. High‐quality evidence means that we are very confident in the results. For pain relief and side effects, we rated the quality of evidence as very low.

We downgraded the quality of the evidence to very low because there were not enough data (e.g. too few participants). For some outcomes the quality of the evidence is unknown because there was no evidence available.

Read the full Cochrane Review here

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\ \ Introduction and aims\ Sprains, strains, and bruises are common injuries, and people with these injuries often require pain relief, given as a tablet or capsule that is swallowed (oral). Many types of oral painkillers are available to treat such injuries. We wanted to know whether there were any differences in people's pain, swelling, function, or unwanted side effects when sprains, strains, and bruises were treated with oral non‐steroidal anti‐inflammatory drugs (NSAIDs, e.g. ibuprofen) compared with paracetamol, opioids (e.g. codeine), complementary or alternative medicines, or combinations of these.\ This is an update of a Cochrane review published in 2015.\ What did we do?\ We searched medical databases up to January 2020 for studies that compared NSAIDs with other painkillers in people with sprains, strains, and bruises. Study participants could be any age. We assessed the included studies to judge the reliability (certainty) of the evidence. We categorised the evidence as being of high, moderate, low, or very low certainty. High certainty means we are confident in the evidence, moderate certainty means we are fairly confident, low or very low certainty means that we are unsure or very unsure of the reliability of the evidence.\ Results of our search and description of studies\ We included 20 studies, with 3305 participants. Seven studies included people with ankle sprain only. Three studies included children only. Most of the participants of the other studies were young adults, and there were slightly more men than women. Few participants were aged over 65 years. Eleven studies compared NSAIDs with paracetamol, six studies compared NSAIDs with opioids, and four studies compared NSAIDs with paracetamol combined with an opioid. Studies reported outcomes at times varying from one hour after taking the medication, up to 10 to 14 days.\ Main results\ There is no difference between NSAIDs and paracetamol in pain after one to two hours, or after two to three days (high‐certainty evidence), and there may be no difference after a week or more (low‐certainty evidence). There is low‐certainty evidence that NSAIDs may make little difference to swelling after a week or more. We are uncertain whether NSAIDs make a difference to return to function after a week or more (very low‐certainty evidence). There is low‐certainly evidence that NSAIDs may slightly increase unwanted side effects related to the gut.\ There is probably no difference between NSAIDs and opioids in pain at one hour (moderate‐certainly evidence), and there may be no difference four or seven days after taking medication (low‐certainty evidence). We are uncertain whether NSAIDs make a difference to swelling after 10 days (very low‐certainty evidence). There is low‐certainty evidence that NSAIDs may increase return to function in 7 to 10 days. There is moderate‐certainty evidence that NSAIDs probably result in fewer unwanted side effects, such as nausea and dizziness, compared with opioids.\ The evidence suggests that there is little or no difference between NSAIDs and paracetamol combined with opioids in pain, swelling, return to function, or unwanted side effects. However, the evidence was very low certainty, so we are uncertain of these results.\ No studies reported the risk of re‐injury after treatment.\ We found no studies comparing NSAIDs with complementary or alternative medicines.\ Conclusions\ The body of evidence to date has found no difference between NSAIDs and other pain killers for pain relief for strains, sprains, and bruises in younger people. However, we need more, and better evidence on return to function and unwanted side effects in all age groups, particularly in older people.](https://app.figure1.com/case-detail/1b22ae79-f8d2-4864-a092-abfc66c02fca)

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