Oral Sedation Using Midazolam in Patients with Alzheimer`s Disease

University of Campinas
Piracicaba Dental School, Brazil
Prof. Dr. Eduardo Hebling
26TH Annual Meeting of SCD
Chicago – April 12, 2014
Associate Professor
Coordinator of Geriatric Dentistry
Specialty Program
[email protected]
Alzheimer`s Disease (AD)
 Most common form of dementia
among the elderly;
 Progressive degenerative brain
Senile plaques
disorder that seriously affects a
person’s ability to carry out their
daily life activities;
Jicha & Carr, 2010
 2050: project to reach 106.8
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million worldwide (affecting 1 in
85 people globally);
 The disease is a growing public
health concern with major
socioeconomic burden.
Brookmeyer et al., 2007
Alzheimer`s Disease (AD)
 The dementia starts slowly. First affects the parts of the brain that control
the thought, the memory and the language;
 People with AD may have difficulty to recall recent events or names of
people who know;
 Over the time, the symptoms worsen;
 There is no cure for the disease;
 Some drugs can help prevent the symptoms becoming worse.
Dental Care Manegement
Alzheimer’s Disease (AD)
Lack of compliance and
cooperation for the
Oral Sedation
Difficulties of care
Ettinger R.F., 1992
Oral Sedation
 Almost universal acceptability;
 Ease of administration;
 Low cost;
 Decreased incidence of adverse reactions;
 Decreased severity of adverse reactions;
 No needles, syringes, equipment;
 No specialized training requirements.
 Reliance on patient compliance;
 Prolonged latent period;
 Erratic and incomplete absorption of drugs
from the gastrointestinal tract;
 Inability to titrate;
 Inability to readily lighten or deepen the level
of sedation;
 Prolonged duration of action.
Midazolam Maleate
 Benzodiazepine drug with fast onset (30-60
minutes), short duration (60 minutes), prompt
rate of half-life elimination (1.5 to 2.5 hr);
 Sedative, anxiolytic, anticonvulsant and muscle
relaxant properties;
 Low toxicity level;
 Hepatic metabolized and renal elimination;
 Induce a short duration amnesia;
 Low cost;
 Easy use (oral via, one hour before the dental
treatment) Yuan et al., 1999
 Flumazenil, a benzodiazepine antagonist drug,
can be used to treat an overdose or to reverse
the sedation (IV: 0.1-0.4 mg/h in 5% glucose)
Girdler et al., 2002
To determine acceptance, safety
and efficacy of oral Midazolam for
conscious sedation in patients
with Alzheimer’s Disease
undergoing dental treatment.
Material and Methods
 Case report study
 Approved by Ethical Committee at University of Campinas
 Informed consent was obtained from the family of all patients
 Developed in dentate elderly with Alzheimer’s Disease
 Living in a Brazilian long-stay institution
 Total population: 450 elderly
Material and Methods
Inclusion Criteria:
- Alzheimer’s Disease
 Stages 6 to 7 (Reisberg’s Scale): severe to very severe cognitive decline
Material and Methods
Exclusion Criteria:
 Presence of respiratory disease (e.g., asthma, cystic fibrosis, emphysema,
chronic obstructive pulmonary disorder –COPD)
 Hypersensitivity by Midazolam
 Previous use of some drugs:
- Macrolide antibiotics (e.g., Azithromycin, Clarithromycin, Erythromycin)
- Ketaconazole (antifungal drug)
- Itraconazole (antifungal drug)
- Ritonavir (antiretroviral drug)
- Amprenavir (antiretroviral drug)
- Nelfinavir (antiretroviral drug)
- Nefazodone (antidepressant drug)
- Rifampin (antibiotic for nonviral infections, such as tuberculosis)
- Carbamazepine (anticonvulsant)
- Phenytoin (anticonvulsant and cardiac antiarrhythmic)
Yuan R, Flockhart DA, Balian JD. Pharmacokinetic and pharmacodynamic
consequences of metabolism-based drug interactions with alprazolam,
midazolam, and triazolam. J Clin Pharmacol. 1999; 39(11): 1109-1125.
May cause
decreased effect
of Midazolam
Material and Methods
 Sedation: Midazolam oral (15 mg), one hour before
Guo T, Mao GF,
Xia DY, Su XY, Zhao LS.
Pharmacokinetics of midazolam tablet in different
Chinese ethnic groups. J Clin Pharm Ther. 2001;
36(3): 406-411.
Romano MM, Soares MS, Pastore CA, Tornelli MJ, de
Oliveira Guaré R, Adde CA. A study of effectiveness
of midazolam sedation for prevention of myocardial
arrthymias in endosseous implant placement. Clin
Oral Implant Res. 2012; 23(4): 489-495.
Sjövalls S, Kanto J, Kangas L, Pakkanen A.
Comparison of midazolam and flunitrazepam for
night sedation. Anaesthesia 1982, 37: 924–928.
The author show no conflict of interest
Material and Methods
 Sedation level: was measured
by Ramsay Sedation Scale
 Local anesthesia: 2% lidocaine
with 1:100,000 epinephrine
Material and Methods
 Pulse oximeter:
 Blood pressure (mmHg)
 Heart rate (beats/min)
 Respiratory rate (breaths/min)
 Saturation of peripheral oxygen (SpO2)
 Sedation and behavioral scores were
recorded every minute.
Material and Methods
 Security Parameters:
- Hypoxemia: SPO2 < 90%, 15 seconds
- Bradycardia: heart rate < 60 beats/min
- Tachycardia: heart rate > 100 beats/min
- Hypotension: decrease of 20% or more in basal systolic
arterial pressure rate (BSAP)
- Hypertension: increase of 20% or more in basal systolic
arterial pressure rate (BSAP)
Jorgensen JS, Schmid ER, Konig V, Faisst K, Huch A, Huch R. Limitations of
forehead pulse oximetry. J Clin Monit. 1995; 11(4):253-256.
Pedersen T, Dyrlund Pedersen B, Møller AM. Pulse oximetry for perioperative
monitoring (Cochrane Review). In: The Cochrane Library. Issue 1; 2007.
Material and Methods
Statistical Analysis
 Analysis of variance for repeated measures: to compare
changes in variable values across time;
 Neuman-Keuls post hoc test: for comparison between pairs of
means where the analysis of variance results were significant
(P < 0.05)
 Linear regression: to determine the correlation coefficients
 Results was expressed by means ± SD
 A total of 65 patients (26 males and 39 females)
 Mean age of 72 years
 The heart and respiratory mean rates for both gender were
similar and within acceptable limits
 The lowest mean of saturation of peripheral oxygen (SPO2)
was 91 % (SD=± 1.7), ranging 91 to 97 %, within safe limits.
Reference Scores of Acute Respiratory Distress (ARD)
Pressure of arterial oxygen (PaO2)
< 60 mmHg
Saturation of peripheral oxygen (SPO2)
< 90 %
Partial arterial pressure of CO2 (PaCO2)
> 50 mmHg
Pedersen T, Dyrlund Pedersen B, Møller AM. Pulse oximetry for perioperative
monitoring (Cochrane Review). In: The Cochrane Library. Issue 1; 2007.
 Level of sedation ranged of 2 to 5.
 Only one patient showed low
sedation level due to concomitant
use of Lorazepam in only one
 Time of drug action after the
dental care: 40 (± 15) minutes
 Local anesthesia and extractions were 90% of the treatments
 Of the 195 dental care sessions:
 92% were performed with total acceptance,
 6% with doubtful acceptance,
 2% no treatment could be performed.
 No complications were registered during or after the dental
care treatment.
One hour before
Ramsey Level 1
(anxious, agitated,
restless )
Starting the dental care
Ramsey Level 2
(co-operative, calm,
Ending the dental care
01 hour
After 40 minutes
Note: Permission of the family to
display images on this patient
End of sedation
Ramsey Level 2
Oral Midazolam is a safe and
effective method of sedation
for dental care in elderly with
Alzheimer`s Disease.
University of Campinas
Piracicaba Dental School, Brazil
Prof. Dr. Eduardo Hebling
[email protected]

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