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Three Part Question

In [patients presenting with acute sickle crisis] are there any [inhaled therapies] which would [reduce pain]

Clinical Scenario

A patient attends A&E with a painful sickle crisis. They have taken oral anlgesia including rescue oramorph with limited effect.
You are unable to obtain IV access and wonder if there are any inhaled therapies (apart from oxygen) which could help the patient.
You ask your registrar who is uncertain so you decide to check BestBETS

Search Strategy

Medline using PubMed overface
(("inhalation"[MeSH Terms] OR "inhalation"[All Fields] OR "inhaled"[All Fields]) AND ("therapy"[Subheading] OR "therapy"[All Fields] OR "therapeutics"[MeSH Terms] OR "therapeutics"[All Fields]) AND sickle[All Fields] AND ("cells"[MeSH Terms] OR "cells"[All Fields] OR "cell"[All Fields]) AND ("Crisis"[Journal] OR "crisis"[All Fields])) AND ("humans"[MeSH Terms] AND English[lang])

Search Outcome

18 articles generated through search
2 relevent articles. One pilot RCT and one full RCT

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Weiner, Hibbard et al. 2003 USA	Pilot study with 20 patients age 10 - 21 with sickle cell and acute vaso-occlusive sickle crisis	Double blind RCT pilot study using inhaled nitric oxide vs placebo	Change in pain at 4 hours using visual analogue scale	No statistical difference in pain at 4, 6 and 24 hours	Pilot study therefore only 20 participants with 80% power Patients were given IV morphine in conjunction with inhaled nitric oxide therefore IV access still required Patients in placebo group were younger than the trial group with statistical significance P= 0.05) Defined as paediatric patients but patients up to age 21 years included in study. No children under age 10 included in study
			Parenteral narcotic use	Statistically less narcotic use in first 6 hours. Overall less use but no statistical significance after 6 hours
			Length of hospitalization	78 hours (mean) for nitric oxide group vs. 100 hours (mean) for placebo group. Not statistically significant (p=0.19)
			Secondary outcomes: BP, SPO2, MetHb levels	No statistically significant difference between the 2 groups

Comment(s)

There are few papers which look at the effect of inhaled treatment for therapy in acute vaso occlusive sickle cell disease. The current evidence only evaluates nitric oxide (which is not the same as nitrous oxide or entonox) and the current RCT's show no evidence that inhaled therapy improves symptoms. Sickle cell disease has a lot of considerations in anaesthetic practice and it must be remembered that hypoxia can cause further sickling and methaemoglobin is also a consideration in the use of inhaled agents.

Clinical Bottom Line

There is no evidence that inhaled therapy can improve symptoms of an acute vaso occluaive crisis in sickle cell disease.

References

1. Weiner, Hibbard et al. Preliminary Assessment of Inhaled Nitric Oxide for Acute Vaso-occlusive Crisis in Pediatric Patients With Sickle Cell Disease JAMA, August 25, 2004—Vol 292, No. 8
2. Gladwin, Kato et al. Nitric Oxide for Inhalation in the Acute Treatment of Sickle Cell Pain Crisis JAMA, March 2, 2011—Vol 305, No. 9