title: Quantification of respiratory depression during pre-operative administration of midazolam using a non-invasive respiratory volume monitor.
abstract: BACKGROUND
  Pre-operative administration of benzodiazepines can cause hypoventilation-a decrease in minute ventilation (MV)-commonly referred to as "respiratory compromise or respiratory depression." Respiratory depression can lead to hypercarbia and / or hypoxemia, and may heighten the risk of other respiratory complications. Current anesthesia practice often places patients at risk for respiratory complications even before surgery, as respiratory monitoring is generally postponed until the patient is in the operating room. In the present study we examined and quantified the onset of respiratory depression following the administration of a single dose of midazolam in pre-operative patients, using a non-invasive respiratory volume monitor that reports MV, tidal volume (TV), and respiratory rate (RR).
  
  
  METHODS
  Impedance-based Respiratory Volume Monitor (RVM) data were collected and analyzed from 30 patients prior to undergoing orthopedic or general surgical procedures. All patients received 2.0 mg of midazolam intravenously at least 20 minutes prior to the induction of anesthesia and the effects of midazolam on the patient's respiratory function were analyzed.
  
  
  RESULTS
  Within 15 minutes of midazolam administration, we noted a significant decrease in both MV (average decrease of 14.3% ± 5.9%, p<0.05) and TV (22.3% ± 4.5%, p<0.001). Interestingly, the corresponding RR increased significantly by an average of 10.3% ± 4.7% (p<0.05). Further analysis revealed an age-dependent response, in which elderly patients (age≥65 years, n = 6) demonstrated greater reductions in MV and TV and a lack of compensatory RR increase. In fact, elderly patients experienced an average decrease in MV of 34% ± 6% (p<0.05) compared to an average decrease of 9% ± 6% (p<0.05) in younger patients.
  
  
  CONCLUSIONS
  We were able to quantify the effects of pre-operative midazolam administration on clinically significant respiratory parameters (MV, TV and RR) using a non-invasive RVM, uncovering that the respiratory depressive effect of benzodiazepines affect primarily TV rather than RR. Such respiratory monitoring data provide the opportunity for individualizing dosing and adjustment of clinical interventions, especially important in elderly patients. With additional respiratory data, clinicians may be able to better identify and quantify respiratory depression, reduce adverse effects, and improve overall patient safety.
authors.affiliation: Neurology Department, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Luis N
authors.initials: LN
authors.lastname: Gonzalez Castro
authors.affiliation: Anesthesiology Department, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
authors.forename: Jaideep H
authors.initials: JH
authors.lastname: Mehta
authors.affiliation: Research Department, Respiratory Motion Inc., Waltham, Massachusetts, United States of America.
authors.forename: Jordan B
authors.initials: JB
authors.lastname: Brayanov
authors.affiliation: Anesthesiology Department, Vidant Medical Center, Greenville, North Carolina, United States of America.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Mullen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000758:Anesthesia / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008176:Lung Volume Measurements; D008297:Male; D008874:Midazolam / Q000009:adverse effects*; D008875:Middle Aged; D008991:Monitoring, Physiologic; D012131:Respiratory Insufficiency / Q000139:chemically induced / Q000503:physiopathology*; D056152:Respiratory Rate / Q000187:drug effects; D013990:Tidal Volume / Q000187:drug effects*
chemical_list: D008874:Midazolam