Uso de Midazolam com oximetria de pulso em pacientes com Alzheimer

Oral sedation using Midazolam in patients with Alzheimer's diseaseProf. Dr. Eduardo Hebling Associate ProfessorCoordinator of Geriatric Dentistry Specialty Programhebling@fop.unicamp.br

University of CampinasPiracicaba Dental School, BrazilUNICAMP26TH Annual Meeting of SCDChicago April 12, 2014Alzheimer`s Disease (AD)Most common form of dementia among the elderly;Progressive degenerative brain disorder that seriously affects a persons ability to carry out their daily life activities; Jicha & Carr, 20102050: project to reach 106.8 million worldwide (affecting 1 in 85 people globally);The disease is a growing public health concern with major socioeconomic burden. Brookmeyer et al., 2007UNICAMP

Font: www.google.com.brSenile plaquesThe 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.UNICAMP Global Deterioration Scale (Reisberg, 1982 )1: No cognitive decline2: Very mild cognitive decline3: Mild cognitive decline4: Moderate cognitive decline5: Moderately severe cognitive decline6: Severe cognitive decline7: Very severe cognitive decline

Alzheimer`s Disease (AD)Alzheimers Disease (AD)UNICAMPLack of compliance and cooperation for the treatmentDifficulties of careOral SedationDental Care ManegementEttinger R.F., 1992

Special Care Dent. 1999; 19(2):56-63.Matear DW, Clarke D.Oral Sedation 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.Disadvantages 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.Advantages 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) 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)Midazolam Maleate

UNICAMPGirdler et al., 2002Yuan et al., 1999To determine acceptance, safety and efficacy of oral Midazolam for conscious sedation in patients with Alzheimers Disease undergoing dental treatment.ObjectiveUNICAMPUNICAMPMaterial 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 Alzheimers Disease Living in a Brazilian long-stay institution Total population: 450 elderly

UNICAMPMaterial and MethodsInclusion Criteria:- Alzheimers Disease Stages 6 to 7 (Reisbergs Scale): severe to very severe cognitive decline ASA IVPhysical status classification system adopted by the American Society of Anesthesiologists (ASA), 1963A patient without systemic disease; a normal healthy patient.A patient with mild systemic disease.A patient with severe systemic disease that limits activity, but is not incapacitating.A patient with incapacitating systemic disease that is a constant threat to life.A moribund patient not expected to survive 24 hours with or without operation.Emergency operation of any variety; E precedes the number indicating the patient`s physical status (e.g., ASA E-IV).ASA IASA IIASA IIIASA IVASA VASA EUNICAMPMaterial and MethodsExclusion 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.Absolute ContraindicationsMay cause decreased effect of MidazolamUNICAMP Sedation: Midazolam oral (15 mg), one hour beforeMaterial and Methods

The author show no conflict of interestGuo 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 Guar 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.Sjvalls S, Kanto J, Kangas L, Pakkanen A. Comparison of midazolam and flunitrazepam for night sedation. Anaesthesia 1982, 37:924928. UNICAMP Sedation level: was measured by Ramsay Sedation Scale Local anesthesia: 2% lidocaine with 1:100,000 epinephrineLevel 6: Patient exhibits no response.Ramsay Sedation ScaleLevel 1: Patient is anxious and agitated or restless, or both.Level 2: Patient is co-operative, oriented, and calm.Level 3: Patient responds to commands only.Level 4: Patient exhibits brisk response to light glabellar tap or loud auditory stimulus.Level 5: Patient exhibits an sluggish response to light glabellar tap or loud auditory stimulus.Material and MethodsUNICAMP 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 MethodsUNICAMP 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)Material and MethodsPedersen T, Dyrlund Pedersen B, Mller AM. Pulse oximetry for perioperative monitoring (Cochrane Review). In: The Cochrane Library. Issue 1; 2007.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. 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 UNICAMPStatistical AnalysisMaterial and Methods 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 limitsResultsUNICAMP

The lowest mean of saturation of peripheral oxygen (SPO2) was 91 % (SD= 1.7), ranging 91 to 97 %, within safe limits.Results

UNICAMPPressure of arterial oxygen (PaO2)Reference Scores of Acute Respiratory Distress (ARD)< 60 mmHgSaturation of peripheral oxygen (SPO2)< 90 %Partial arterial pressure of CO2 (PaCO2)> 50 mmHgPedersen T, Dyrlund Pedersen B, Mller 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 session. Time of drug action after the dental care: 40 ( 15) minutesResultsUNICAMPLevel 6: Patient exhibits no response.Ramsay Sedation ScaleLevel 1: Patient is anxious and agitated or restless, or both.Level 2: Patient is co-operative, oriented, and calm.Level 3: Patient responds to commands only.Level 4: Patient exhibits brisk response to light glabellar tap or loud auditory stimulus.Level 5: Patient exhibits an sluggish response to light glabellar tap or loud auditory stimulus. 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.ResultsUNICAMP

Note: Permission of the family to display images on this patient

Starting the dental careEnding the dental careAfter 40 minutes

Ramsey Level 1 (anxious, agitated, restless )One hour beforeRamsey Level 2 (co-operative, calm, oriented)Ramsey Level 2 maintainedEnd of sedationUNICAMP01 hour

Oral Midazolam is a safe and effective method of sedation for dental care in elderly with Alzheimer`s Disease.ConclusionUNICAMPProf. Dr. Eduardo Heblinghebling@fop.unicamp.brUNICAMPUniversity of CampinasPiracicaba Dental School, Brazil