Is there a role for inhaled therapy in sickle cell crisis?
Date First Published:
October 26, 2011
Last Updated:
October 27, 2011
Report by:
Emma Green, CT3 (Royal Manchester Childrens Hospital)
Search checked by:
Emma Green, Royal Manchester Childrens Hospital
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
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
Search Details:
(("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])
Outcome:
18 articles generated through search
2 relevent articles. One pilot RCT and one full RCT
2 relevent articles. One pilot RCT and one full RCT
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| Preliminary Assessment of Inhaled Nitric Oxide for Acute Vaso-occlusive Crisis in Pediatric Patients With Sickle Cell Disease 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 | ||||
| Nitric Oxide for Inhalation in the Acute Treatment of Sickle Cell Pain Crisis Gladwin, Kato et al. 2011 USA | Patients aged over 10 years presenting with acute vaso occlusive crisis with known sickle cell diseease | Prospective, multicenter, double-blind, randomized, placebo-controlled clinical trial for up to 72 hours of inhaled nitric oxide gas vs inhaled nitrogen placebo in 150 participants presenting with vaso occlusive crisis of sickle cell disease at 11 centres between October 5, 2004, and December 22, 2008. |
Small study number (150) despite high numbers of eligable patients Long list of conflicts of interest declared by authors Overlapping of confidence intervals with broad ranges for primary outcome means that small differences may not have been detected Patients who withdrew from treatment were still included in the overall evaluation. These patients were recorded in the consort diagram |
Author Commentary:
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.
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.
Bottom Line:
There is no evidence that inhaled therapy can improve symptoms of an acute vaso occluaive crisis in sickle cell disease.
References:
- Weiner, Hibbard et al.. Preliminary Assessment of Inhaled Nitric Oxide for Acute Vaso-occlusive Crisis in Pediatric Patients With Sickle Cell Disease
- Gladwin, Kato et al.. Nitric Oxide for Inhalation in the Acute Treatment of Sickle Cell Pain Crisis