15 years old girl #without-symptoms reported. She started a | Figure 1

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15 years old girl #without-symptoms reported. She started a year ago with this lesion that had increased its #size from 1cm to 5cms. #Blood_smear reported as follows: Hb: 10, anysocytosis, hypocromic rbc, few microcytic cells, few target cells. Plts: 340

Review question

We reviewed the evidence about the effects of inhaled nitric oxide for relieving pain crises in people with sickle cell disease.

Background

Sickle cell disease is a condition that affects the red blood cells. Normal red blood cells are round, but in people with sickle cell disease some of the red blood cells can have an abnormal shape. They look like a crescent (or an old-time tool called a 'sickle'). The abnormally-shaped cells easily become stuck in blood vessels which can cause episodes of severe pain called 'pain crises'. The pain can be in the bones, chest, or other parts of the body, and can last from several hours to days. Painkillers are the main treatment of these pain crises. Another suggested treatment is inhaled nitric oxide, which is a gas that can relax the blocked blood vessels so they can widen and allow the sickled cells to pass. We wanted to evaluate whether inhaled nitric oxide is effective in relieving pain in people with sickle cell disease.

Search date

The evidence is current to: March 2018.

Trial characteristics

The review included three trials with 188 people (equal numbers of males and females) with sickle cell disease who were experiencing a pain crisis. Most participants were adults, except for one trial conducted in a children's hospital where most participants were children over 10 years of age. The trials compared inhaled nitric oxide with a control (room air), which does not provide pain relief, and people were selected for one treatment or the other at random. The treatments in two trials lasted for four hours and in the third trial lasted for eight hours.

Key results

Only one large trial (150 participants) reported no difference in the time until the pain stopped between nitric oxide or room air. This trial was also the only trial to report on the frequency of pain crises in the follow-up period and we found little or no difference between inhaled nitric oxide and room air for a return to the emergency department or for re-admission to hospital. All three trials reported pain scores; the larger trial found no difference between nitric oxide or room air at each time-point up to eight hours, but the two smaller trials (38 participants) reported a benefit of inhaled nitric oxide in relieving the pain after four hours, but these trials were small and limited compared to the first trial.

All three trials reported that inhaled nitric oxide had no effect on decreasing the use of painkillers, but did not provide any data we could analyse. Two trials reported the average duration of stay in hospital; in the large trial those who were given room air had a shorter stay, and one of the smaller trials (at the children's hospital) reported a shorter stay in those treated with inhaled nitric oxide. Only the larger trial reported harmful effects of nitric oxide and found that treatment made little or no difference.

We could not combine the available data from the three included trials due to differences in the reporting of outcomes. Therefore, the currently available evidence is not enough to give a definitive answer about the use of inhaled nitric oxide for people with sickle cell disease experiencing a pain crisis.

Future trials, preferably large-scale and long-term, should be carried out to provide strong evidence in this area. Investigators should measure and report outcomes important to patients (e.g. measures of pain and time to pain resolution and amounts of analgesics used) as well as use of healthcare services in a standardised way.

Quality of the evidence

We judged the evidence we were able to analyse to be of low quality. We believe that the results in this review were affected because not all planned outcomes were reported in two of the trials and the trials were only small. Furthermore, the fact that the pharmaceutical industry financed the smaller adult trial should be considered when looking at the results of this trial.