title: Intrathecal inflammatory masses: is the yearly opioid dose increase an early indicator?
abstract: OBJECTIVE
  The objective of this study is to investigate the association between intrathecal drug, flow rate, drug concentration, and drug dose with the formation of intrathecal inflammatory masses.
  
  
  METHODS
  A retrospective longitudinal study of 56 consecutive patients receiving long-term intrathecal analgesic administration was undertaken through screening of medical records. Data regarding drug flow rate, dose per day, and concentration of drugs administered were recorded for morphine, diamorphine, bupivicaine, clonidine and baclofen and averages computed.
  
  
  RESULTS
  The average follow-up time post-implant was 91 ± 55 months (range: 9-209). Four of the 56 patients were diagnosed with intrathecal granuloma indicating a rate of 7%, the equivalent to 0.009 events per patient year. Twenty-one of the patients had received morphine either alone or combined; 22 had received diamorphine either alone or mixed; and 13 crossed over from morphine to diamorphine or the inverse. None of the patients with granuloma crossed over before diagnosis. A significant correlation was found between opioid dose (r= 0.275, p < 0.05), yearly increase of the opioid dose (r= 0.433, p < 0.05), and granuloma formation. Clonidine appeared to have a protective effect for the non-granuloma patients. No association was found with flow rate (r= 0.056) or opioid concentration (r= 0.214).
  
  
  CONCLUSIONS
  This is the first detailed study showing an association of diamorphine with granulomas. This study supports the previous finding of intrathecal opioid dose being a risk factor for intrathecal granulomas and clonidine being protective. In addition we have found that the yearly increase in opioid dose is a risk factor for granulomas and could serve as an indicator for closer surveillance.
authors: Faculty of Health, Birmingham City University, Birmingham, UK;             Department of Pain Management, Russells Hall Hospital, Dudley, UK; and             Pain Management Unit, University Hospital Birmingham, Birmingham, UK.
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authors: RV
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