Bronchoscopy and Bispectral Index (BIS) - Guided Sedation
Condition: Bronchoscopy
Study type: Interventional
Phase: Phase 4

Summary: 
      Bronchoscopy is performed on a daily basis for diagnostic and therapeutic purposes. This
      procedure may cause anxiety and discomfort requiring the use of sedative drugs.

      In this study the investigators titrate the administration of sedatives using bispectral
      analysis of the EEG. The investigators compared 2 drugs, propofol versus midazolam regarding
      patient subjective tolerance, recovery of brain function, safety and operator's satisfaction.
    

Detailed description: 
      Sedation using anxiolytic, hypnotic and /or analgesic drugs is currently used during flexible
      bronchoscopy (FB) to facilitate the diagnostic process and improve patient comfort.[The
      technique of sedation varies widely and depends primarily on the experience of the chest
      physician. FB can also be done without sedation. However, according to a recent survey, 80%
      of patients prefer to be sedated during FB and it is also well known that the operator has a
      tendency to overstate the tolerance of patients during the procedure.

      The use of benzodiazepines for sedation undoubtedly enhances the perception and tolerance
      during FB and they are by far the most widely used drugs because of their ease of
      administration, their speed of action and the possibility to administer an antidote. The
      drawback of these sedative agents is related to a high variable individual sensitivity, which
      can lead to drug overdose and to severe respiratory depression requiring ventilatory
      assistance. In addition, their sedative and amnesic effects might persist several hours after
      the procedure.

      Over the last decade, major advances in technology and pharmacology have resulted in better
      cerebral monitoring of anaesthesia with tools like electroencephalographic bispectral index
      and synthesis of sedative agents of short duration of action as propofol (P).

      P is a lipidic emulsion used intravenously for induction and maintenance of anaesthesia. Its
      effect begins rapidly and ends faster than midazolam (M). The main advantage of P is
      therefore a faster recovery of mnesic, cognitive and motor functions, whereas M induces
      anterograde amnesia (1-2 h after bolus) and slower motor reaction . This gives to P a keen
      interest in ambulatory practice. While P is commonly and safely used in several
      gastroenterological endoscopic procedures, its use by pneumologist is currently hampered by a
      lack of expertise and could benefit from collaboration with the anaesthesia team.

      This is a randomised trial comparing recovery of brain function and patient subjective
      tolerance following FB after administration either of P or M for sedation. Patients and
      operators are blinded to the sedative drug, which is administered and titrated by another
      chest physician.

      For each procedure, the staff consists of a chest physician trained in FB (operator), a
      physician in charge of sedation and two nurses for technical assistance and proper data
      recording. Before the procedure, blood pressure (BP), heart rate (HR), oxygen saturation
      (SaO2) and weight are recorded. The patient is placed in supine position, fitted with a nasal
      oxygen cannula and a peripheral intravenous access (18-20 G) for the infusion of
      crystalloids. Oxygen is administered only if SaO2 was < 92%. Local anaesthesia is done using
      lidocaïne 10 % and 1% in the pharynx and central airways respectively. The sedative drugs
      syringes and lines are hidden from the operator by a sheet. Sedation is then started with P
      or M according to randomization for any FB as follows: We inject in both groups a 5 ml bolus
      of lidocaine 1% (50 mg) (prevention of pain associated with P injection), followed by either
      a 40 mg (4 ml) bolus of P or 2 mg of M. The re-injection of 20 mg (2ml) of P or 2 mg of M was
      allowed every 2 minutes to achieve and maintain BIS values between 70 and 85 and OAA/S of
      3-4. Blood pressure, oxygen saturation, heart rate, BIS and OAA/S are monitored continuously
      and recorded every 3 minutes during the procedure and at 5, 15, 30, 45 and 60 minutes after
      its end. We record the time necessary to achieve the targeted BIS value after the injection
      of the sedative drug, the duration of FB, the electroencephalographic recovery time, defined
      as the time to reach a BIS value > 90 after the end of FB and total doses of M and P.

      Sixty minutes and 24 hours after FB, operator and patient, both blinded to the allocation,
      evaluate the tolerance to the FB with visual analogic scales (VAS) (1 mm: excellent
      tolerance, 100 mm very low tolerance) to assess 1) the global tolerance of the procedure and
      2) the intensity of 4 key symptoms during FB (pain, nausea, breathlessness and cough).

      Before the procedure and 15 and 60 minutes after the procedure, patients are asked to
      complete CPT trials to evaluate cognitive recovery.
    

Intervention name(s): Propofol; Midazolam
Intervention type(s): Drug; Drug
Intervention description(s): i.v. propofol titration until adequate depth of sedation; i.v. midazolam titration until adequate depth of sedation
Intervention MeSH terms: Midazolam; Propofol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment
Keywords: bispectral analysis; bronchoscopy; midazolam; propofol; recovery; sedation