| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1
Department of Anaesthesiology, Medical School of Hannover, Carl-Neuberg-Str.
1, 30625 Hannover, Germany.
2
Present address: University Department of Anaesthesiology, The University of
Liverpool, Duncan Building, Daulby St., Liverpool L69 36A, United
Kingdom.
3
Department of Neuroradiology, Medical School of Hannover, 30625 Hannover,
Germany.
Received July 6, 2000;
accepted after revision September 19, 2000.
Address correspondence to S. Münte.
Abstract
 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
SUBJECTS AND METHODS. Fifty-four patients scheduled for MR imaging were included in this prospective study. Anxiety and sedation of patients were evaluated before drug administration, immediately before MR imaging, and at the end of the procedure. The Spielberger State-Trait Anxiety Inventory, the visual analogue scale of anxiety, and a five-point sedation scale were used. Half the patients received intranasal spray applications of 4 mg midazolam, whereas the other patients received a placebo, in a randomized, double-blind study design (six sprayings of 0.5% midazolam solution or NaCl 0.9%, respectively). The intensity of the sensation of burning of the nasal mucosa was rated by patients using a three-point scale (no, slight, or strong burning). The quality of scan images was evaluated by a radiologist using a five-point scale (0 = extremely poor, 5 = excellent).
RESULTS. No cancellations occurred with patients who received midazolam, whereas four of 27 patients receiving placebo panicked and terminated the scanning procedure. The initial anxiety and sedation scores did not differ between the groups. Patients who received midazolam spray were more sedated and less anxious immediately before entering the MR scanner and reported a more intense slight transient burning of the nasal mucosa than those in the placebo group. The quality of the MR image was higher in the midazolam group.
CONCLUSION. A sizeable reduction in MR imaging—related anxiety and improved MR image quality were seen with patients who received intranasal midazolam spray. With the exception of transient burning of the nasal mucosa, no adverse effects were reported. This simple and safe method is useful in sedating patients for MR imaging and other minor procedures.
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Benzodiazepines are the most frequently used drugs in clinical situations
associated with anxiety and panic reactions
[6]. For minor therapeutic and
diagnostic procedures, midazolam seems to be superior to other benzodiazepines
because of its short duration of action (20-40 min) and elimination half-life
of only 1 hr 30 min to 3 hr. The anxiolytic and sedative effects can be
observed after relatively low doses, which are associated with minimal risks
[7]. Midazolam is applicable
via IV, intramuscular, oral, rectal, and intranasal routes. The necessity of
venous cannulation may be a disadvantage of IV administration. Moreover, IV
administration requires additional monitoring of respiratory function (pulse
oxymetry), which can be difficult in an MR scanner. The intranasal route
appears to offer a significant advantage over orally or rectally administered
midazolam because it bypasses the portal system and does not underlie the high
hepatic first-pass elimination. Midazolam is rapidly absorbed from the highly
vascular nasal mucosa directly into the systemic circulation and, therefore,
has a higher systemic availability than for other methods of administration
(
50%) with an onset of action within minutes
[8,
9]. Given as an intranasal
spray instead of drops, the absorption of midazolam via nasal mucosa has been
reported to be virtually complete (83%) because little of the substance is
swallowed [10]. The rapid
onset of action has also been explained by direct connections between nasal
mucosa and brain via perineurium of the olfactory nerves
[9,
11,
12].
The purpose of this study was to examine the effect of midazolam nasal spray on anxiety and MR image quality in patients scheduled for MR examination using a double-blind, placebo-controlled design. Moreover, we wanted to develop a simple and safe application technique for midazolam for clinical use in anxious patients. Only MR images of the head or upper body were studied, because these have been reported to evoke more subjective anxiety than MR imaging of the lower body [13].
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Midazolam Spray and Placebo Spray
The drug was administered as a standard injectable solution ([midazolam]
Dormicum 5 mg/mL, Hoffmann-La Roche, Grenzach-Wyhlen, Germany; or 0.9% NaCl)
with a spray bottle, with three successive puffs into each nostril. The spray
bottle delivered a fine aerosol and the mean midazolam dose per activation was
0.675 mg (range, 0.582-0.745 mg). Thus, each patient of the verum group
received an average dose of 4 mg (range, 3.5-4.5 mg) midazolam.
Spielberger State-Trait Anxiety Inventory
The German version of the Spielberger State-Trait Anxiety Inventory form X1
was used to measure state anxiety (how one feels at a particular moment), and
form X2 was used to assess trait anxiety (how one usually feels). The state
anxiety score is based on 20 items for which a person rates anxiety on a scale
from 1 (almost never) to 4 (very much so). The trait anxiety score is composed
in a similar fashion with 20 questions designed to measure anxiety. The
Spielberger State-Trait Anxiety Inventory has previously been validated for
various situations and populations in several studies
[14,
15]. Each questionnaire
required 3-5 min for completion.
Visual Analogue Scale of Anxiety
The Visual Analogue Scale of Anxiety comprised an undivided 100-mm line,
with 0 meaning "I am not anxious at all," and 100 meaning "I
am extremely anxious." Patients were instructed to mark one point on the
line that corresponded to the intensity of their anxiety at that moment. Such
scales have been widely used in psychiatry and anesthesia to assess pain and
other sensations and emotions
[16].
Sedation Score
Patient sedation was evaluated by one of the authors using a five-point
sedation scale (1 = agitated, noncooperative; 2 = alert, restless; 3 = calm,
eyes spontaneously open; 4 = drowsy, responds to minor stimulation; 5 =
asleep, rousable but does not respond to minor stimulation). The scale was
devised by Wilton et al. [17]
to evaluate level of sedation of preschool children who had received
intranasal midazolam drops for sedation before anesthesia for surgery.
MR Image Quality
The scan quality was evaluated by the radiologist at the end of the
procedure using a five-point scale (1 = very poor, 2 = poor, 3 = satisfactory,
4 = good, 5 = excellent).
Physiologic Status
Heart rate and oxygen saturation were continuously monitored during the
study period. Movements were observed through the window between the scan room
and computer desk and through a video camera focused on the patient. All
patients held an alarm button and received instructions to push it if they
panicked and needed to terminate scanning.
Procedure
MR imaging was performed on a 1.5-T Signa Advantage scanner (General
Electric Medical Systems, Milwaukee, WI). A session began with the patients
completing form X1 of the Spielberger State-Trait Anxiety Inventory.
Thereafter, patients rated their anxiety using the visual analogue scale.
Midazolam was administrated 15 min before MR imaging. The sensation of burning
of the nasal mucosa was rated by patients using a three-point scale (1 = no
burning, 2 = slight burning, 3 = strong burning). The intensity of nose
burning was noted. The administrator of the medication (or placebo) was not
aware of which of the two substances was contained in the spray bottle.
Anxiety and sedation of patients were measured a second time immediately
before the participants entered the MR scanner. Immediately after MR imaging,
the State-Trait Anxiety Inventory and visual analogue scale were administered,
and sedation was estimated before the patients were brought back to the
ward.
The results are presented as mean values ± standard deviation. Statistical analysis was performed using different methods for different data subsets. For qualitative variables (sex, termination of scan) the two-tailed chi-square test was used. Quantitative variables having a normal distribution (state and trait anxiety, self-estimated anxiety using the visual analogue scale, scan time, and age) between groups were analyzed using the Student's t test. Sedation scale, intensity of nose burning, and MR image quality between groups were analyzed using nonparametric data analysis. Statistical significance was accepted if p was less than 0.05.
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
|
Data on anxiety, sedation, nose burning, and MR image quality before and after imaging are presented in Table 2. The initial measurements of anxiety and sedation revealed no significant differences between groups. When compared with patients who received placebo, patients who had received intranasal midazolam spray showed significantly lower anxiety scores and higher sedation scores 15 min after medication and immediately before MR imaging. After MR imaging, the anxiety scores of both groups returned to baseline values. Patients in the midazolam group remained sedated after the scan, whereas the alertness of the placebo group remained unchanged.
|
MR image quality was significantly better in the midazolam group (p < 0.0001) and ranged from good to excellent. MR image quality of those in the placebo group ranged from very poor (not usable) to good. There was more intense nose burning reported by patients in the midazolam group (strong [n = 3], slight [n = 15], or no burning [n = 9]) than in the placebo group (slight [n = 9] or no burning [n = 18]) (p < 0.008). The oxygen saturation remained above 95% during MR imaging for all patients. No patient needed follow-up in a postanesthesia ward.
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Intranasal midazolam (0.5% ampule solution) has been described previously for dental and endoscopic procedures [18, 19], for treatment of panic disorders [7], and for preanesthetic sedation of children [8, 17]. With doses between 0.1 and 0.3 mg/kg, a sedative effect is achieved in about 10 min, which correlates with the peak plasma concentration of midazolam. Burstein et al. [9] reported that one of eight volunteers became lethargic, hypotensive, and difficult to arouse shortly after receiving 0.25 mg/kg intranasal midazolam. These symptoms reversed promptly after IV administration of 2 mg flumazenil. No cardiovascular adverse effects have been reported using doses of 0.2 mg/kg or less. To our knowledge, intranasal midazolam spray has been described in only one study, which reported a bioavailability of 83% after a single bolus of 0.15 mg/kg, compared with that of the IV route (100%). Thus, the standard IV dose should be reduced to avoid overdose [10]. Doses much below those needed for sedation should be sufficient to prevent panic reactions. In a pilot study, Schweizer et al. [7] reported improvement of panic disorder in four of five patients using a total dose of 0.5-1.0 mg of self-administrated intranasal midazolam drops. We achieved effective anxiolysis using an average dose of 4 mg (range, 0.04-0.08 mg/kg) midazolam.
Intranasal midazolam spray has a number of advantages over other administration methods. In contrast to its effectiveness via oral and rectal routes, the drug's effectiveness is not reduced by the presence of gastric contents or the hepatic first-pass metabolism. Unlike intranasal liquid applied with a syringe, the spray is not partly swallowed and the resorption from nasal mucosa is virtually complete. It is also noninvasive, which may be better tolerated by anxious patients than IV injection.
Which patients could benefit from intranasal midazolam spray medication before MR imaging? Fear assessment before MR imaging has been suggested by several authors to identify those at risk (about 10% of patients) for developing claustrophobic symptoms [2, 13]. Questions related to fear and anxiety experienced in situations such as standing in an elevator with the doors closed, lying on the lower bunk bed, working under a sink, having hands tied behind one's back, or having legs tied to an immovable chair may help reveal those who could benefit from anxiolytic medication. For example, Moss et al. [20] administered intranasal midazolam drops to patients who reported a history of claustrophobic symptoms (10%) in a noncontrolled, nonrandomized study. Using a total dose of 0.5-1.0 mg, they dramatically reduced the number of patients needing additional IV sedation (from 67% to 17%) compared with patients who were sedated with conventional sedatives such as oral diazepam and diphenhydramine or chloral hydrate.
The advantages of intranasal midazolam spray (rapidity of onset, ease of administration, and avoidance of an IV injection) outweigh the single disadvantage of a moderate transient burning of the nasal mucosa. Using a low-dose (4 mg) intranasal midazolam spray we found that MR imaging-related claustrophobia and motion artifacts were reduced, and repeated scans and termination of the examination were avoided. Thus, considerable MR imaging cost-savings can be expected with this simple technique. Moreover, patients may benefit from the better diagnostic value of the improved clarity of the MR images.
Acknowledgments
We thank our pharmacist, Hardi Juergen Kniffka, for the measurements of
midazolam sprayings.
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Karst, M. Winterhalter, S. Munte, B. Francki, A. Hondronikos, A. Eckardt, L. Hoy, H. Buhck, M. Bernateck, and M. Fink Auricular Acupuncture for Dental Anxiety: A Randomized Controlled Trial Anesth. Analg., February 1, 2007; 104(2): 295 - 300. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
