Inhaled nitric oxide for treating pain crises in people with | Figure 1

%27%3e%3cg%20id=%27Group-14%27%20transform=%27translate(13.000000,%20103.176124)%27%3e%3cg%20id=%27Group-Copy-5%27%20transform=%27translate(0.000000,%20182.676124)%27%3e%3crect%20id=%27Rectangle-8%27%20fill=%27%23E2E0DE%27%20x=%270%27%20y=%270%27%20width=%2736%27%20height=%2736%27%20rx=%2718%27%3e%3c/rect%3e%3cpath%20d=%27M28,27.6503435%20C28,22.127496%2023.5228474,17.6503435%2018,17.6503435%20C12.4771525,17.6503435%208,22.127496%208,27.6503435%20M18,16.3472505%20C20.8165136,16.3472505%2023.099749,14.0640151%2023.099749,11.2475015%20C23.099749,8.43098783%2020.8165136,6.1477524%2018,6.1477524%20C15.1834863,6.1477524%2012.9002509,8.43098783%2012.9002509,11.2475015%20C12.9002509,14.0640151%2015.1834863,16.3472505%2018,16.3472505%20Z%27%20id=%27Combined-Shape%27%20fill=%27%23FFFFFF%27%20fill-rule=%27nonzero%27%3e%3c/path%3e%3c/g%3e%3c/g%3e%3c/g%3e%3c/g%3e%3c/svg%3e)

Deleted account

Some actions are only available when you log in.

Report case

Report this to our moderators

Inhaled nitric oxide for treating pain crises in people with sickle cell disease

You can view up to 4 cases without signing up Sign up for unlimited access

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 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.

Read the full Cochrane Review here

Comment

Sign up to add a comment

More about this case

ResolvedVerified literature

Why you should join Figure 1

Sign up to explore now

Similar cases

\ \ We reviewed the evidence on the effect of drugs that aim to prevent people with sickle cell disease losing protein or albumin (a protein made in the liver) in their urine.\ Sickle cell disease is a group of inherited conditions that often lead to kidney damage. High protein or albumin levels in urine is a strong predictor of future kidney failure. Angiotensin‐converting enzyme (ACE) inhibitors are often given to reduce the level of protein or albumin in urine and to protect the kidneys from damage. However, we do not know very much about how effective and safe these are in people with sickle cell disease.\ The evidence is current to: 22 August 2021.\ We only included one study (with 22 adults with sickle cell disease) in the review. The participants had high levels of protein (proteinuria) or albumin (microalbuminuria) in their urine and were randomly selected to be treated for six months with either captopril (an angiotensin‐converting enzyme inhibitor) or placebo (dummy drug with no active medication).\ The results from this small and very low‐quality study were not convincing. This study did not show that ACE inhibitors could reduce the level of protein or albumin in the urine. The levels of creatinine (a chemical compound left over from energy‐producing processes in muscles; a high level can indicate kidney failure) and potassium in the blood were reported as constant throughout the study. No serious adverse events were noted, although the potential for causing low blood pressure should be highlighted. More long‐term studies involving multiple centers and larger numbers of participants are needed.\ Certainty of the evidence\ Overall certainty of the evidence was very low, since we thought there was either a high or unclear risk of bias from all aspects that may contribute to biasing the results (e.g. randomisation, the way treatment allocations were concealed, whether all participants recruited were analysed, whether all planned outcomes were reported, as well as blinding of participants, research personnel and outcome assessment).](https://app.figure1.com/case-detail/1719ba9a-cd65-4747-b14d-dac5a5f26ea0)

\ \ An overview of Cochrane Reviews on red blood cell transfusions to treat or prevent sickle cell disease-related complications; 15 reviews met the inclusion criteria for this overview. However, only four reviews (which included nine trials and 1052 participants) had results that could be reported.\ Key results\ In the four reviews there was no difference in the risk of death with any comparison. We found that long-term red blood cell (RBC) transfusions compared to standard care, probably decrease the risk of stroke in children and adolescents at high risk of stroke (abnormal transcranial doppler (TCD) ultrasound (high blood flow to the brain) or a previous silent stroke (a stroke with no outward symptoms and where a person is typically unaware they have suffered a stroke)) and may also decrease their risk of painful crisis and acute chest syndrome.\ Red blood cell transfusions may also decrease the risk of silent stroke in children with abnormal TCD ultrasound when compared to standard care.\ There was a lack of evidence for treating adults with SCD-related complications and that important outcomes, including quality of life were often not measured or reported.\ The quality of the trials included in the reviews was variable across the trials and in relation to the outcomes.](https://app.figure1.com/case-detail/1b61f171-ae36-4c55-9188-3e038af13ce5)

\ \ 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.](https://app.figure1.com/case-detail/2073455e-639a-40c4-b80e-7f40e88aebc6)

\ \ Antibiotics for treating acute chest syndrome in people with sickle cell disease\ Review question\ We reviewed the evidence about the effects and safety of antibiotics (alone or in combination) as compared to other antibiotics, placebo (a 'dummy' treatment) or standard treatment. We wanted to know if the different antibiotic treatments were effective, if they were safe, and which doses worked best for treating acute chest syndrome in people with sickle cell disease. This is an update of a previously published Cochrane Review.\ Background\ Sickle cell disease affects millions of people throughout the world. Acute chest syndrome is a major cause of illness and death in people with sickle cell disease. Symptoms include fever, chest pain and a raised white blood cell count. Acute infection of the lung tissue is a major cause of acute chest syndrome. Antibiotics are often given to treat these lung infections, but there is no worldwide standard treatment.\ Search date\ The evidence is current to: 10 July 2019.\ Study characteristics\ This update was unable to find any trials to include in this review.\ Key results\ While we conclude that a randomised controlled trial should attempt to answer these questions, we do not envisage further trials of this intervention will be conducted, and hence the review will no longer be regularly updated. Until there is firm evidence, clinicians should treat acute chest syndrome on a case by case basis and according to the diagnosis and the treatment available.](https://app.figure1.com/case-detail/4d343811-bfe8-4c1f-ae28-0784721483ad)

Trending now

\ \ A 52-year-old man presented with a 20-minute history of chest pain radiating to the left shoulder and neck, associated with dyspnea and diaphoresis.\ He had a history of hypertension, long-term smoking, and a sedentary lifestyle.\ On physical examination, bibasilar crackles were noted on lung auscultation. An electrocardiogram (ECG) was performed in the primary care setting, and the patient was promptly referred to the emergency department.](https://app.figure1.com/case-detail/ae0fe999-6875-4474-94f0-ad823dbb9b3a)

\ \ A 28-year-old woman presented with a 3-day history of intense pruritus over the lower back. She reported no recent travel or exposure to new environments. She cares for a small kennel with approximately eight dogs rescued from the streets.\ Physical examination revealed multiple small vesicles, some clustered and others scattered, predominantly involving the lumbar region and the left gluteal area.](https://app.figure1.com/case-detail/c271070f-2bc7-4052-9895-635277e1a7d5)

\ \ A 4-month-old male infant presented with skin lesions localized to the chin for the past 3 days. Physical examination revealed multiple small pustules with surrounding inflammatory signs on the chin, along with a few scattered papules on the chest.](https://app.figure1.com/case-detail/48f41642-b9db-4089-b120-a94ee52328de)

\ \ patient in late teens presenting after a collapse, no chest pain, no previous cardiac history, no history of sudden death in family, are there any features in this ekg that would warrant further work-up or is this just a pediatric ekg?](https://app.figure1.com/case-detail/2af390e1-ace8-40ed-ba1c-98fb2d72f4c5)