title: Severe prolonged sedation associated with coadministration of protease inhibitors and intravenous midazolam during bronchoscopy.
abstract: OBJECTIVE
  To determine whether human immunodeficiency virus (HIV)-positive patients who received intravenous midazolam during an inpatient bronchoscopy procedure were more likely to experience severe prolonged sedation if they were taking antiretroviral therapy that included a protease inhibitor versus those who were not taking any antiretroviral therapy.
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  Tertiary care academic medical center.
  
  
  METHODS
  Two hundred forty-one HIV-positive adults who received intravenous midazolam while undergoing bronchoscopy between January 1, 2003, and December 31, 2006, were analyzed; 51 patients were taking an antiretroviral regimen that included a protease inhibitor (exposed group), whereas 190 patients were not taking any antiretroviral agents (nonexposed group).
  
  
  RESULTS
  Patient demographics, medication administration records, and bronchoscopy data were collected from electronic databases and patient medical records. The exposed and nonexposed groups had similar demographic characteristics except that patients in the exposed group had lower HIV viral loads and were less likely to have altered mental status or respiratory distress before bronchoscopy. In addition, the exposed group had a higher proportion of males and patients with hepatitis B or C virus coinfection. The incidence of severe prolonged sedation was 9.80% in the exposed group versus 1.58% in the nonexposed group (relative risk [RR] 6.21, 95% confidence interval [CI] 1.53-25.12). Specific protease inhibitors associated with severe prolonged sedation were atazanavir-ritonavir and lopinavir-ritonavir. Length of hospital stay was approximately 3 days longer in the exposed group compared with the nonexposed group.
  
  
  CONCLUSIONS
  Although the interaction between intravenous midazolam and protease inhibitors is well known, this study was the first systematic evaluation, to our knowledge, of the risk of severe prolonged sedation in a cohort of hospitalized HIV-positive patients. Coadministration of protease inhibitors with intravenous midazolam was associated with severe prolonged sedation as well as increased length of hospital stay. Therefore, concomitant use of these drugs should be closely monitored, or alternative sedatives for procedural sedation should be considered.
authors.affiliation: Department of Pharmacy, The Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD 21287, USA. ajenh1@jhmi.edu
authors.forename: Alice Jenh
authors.initials: AJ
authors.lastname: Hsu
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Carson
authors.forename: Rex
authors.initials: R
authors.lastname: Yung
authors.forename: Paul A
authors.initials: PA
authors.lastname: Pham
mesh_terms: D000328:Adult; D001999:Bronchoscopy; D015331:Cohort Studies; D016208:Databases, Factual; D054810:Deep Sedation; D004347:Drug Interactions; D057286:Electronic Health Records; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D007275:Injections, Intravenous; D007902:Length of Stay; D008297:Male; D008874:Midazolam / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D017320:HIV Protease Inhibitors; D006993:Hypnotics and Sedatives; D008874:Midazolam