RESUMEN

This work investigated interactions ascribed to the administration of phytomedicines containing Valeriana officinalis and Piper methysticum with conventional drugs. The phytomedicines were characterized by HPLC and administered per os to male Wistar rats, either concomitantly or not with the CYP3A substrate midazolam. To distinguish between the presystemic or systemic effect, midazolam was given orally and intravenously. The effects on the P-gp substrate fexofenadine uptake by Caco-2 cells were examined. The valerenic acid content was 1.6 ± 0.1 mg per tablet, whereas kavain was 13.7 ± 0.3 mg/capsule. Valerian and kava-kava extracts increased the maximum plasma concentration (Cmax) of midazolam 2- and 4-fold compared to the control, respectively. The area under the plasma concentrations versus time curve (AUC(0-∞)) was enhanced from 994.3 ± 152.3 ng.h/mL (control) to 3041 ± 398 ng.h/mL (valerian) and 4139 ± 373 ng.h/mL (kava-kava). The half-life of midazolam was not affected. These changes were attributed to the inhibition of midazolam metabolism by the enteric CYP3A since the i. v. pharmacokinetic of midazolam remained unchanged. The kava-kava extract augmented the uptake of fexofenadine by 3.5-fold compared to the control. Although Valeriana increased the uptake of fexofenadine, it was not statistically significant to that of the control (12.5 ± 3.7 ng/mg protein vs. 5.4 ± 0.3 ng/mg protein, respectively). Therefore, phytomedicines containing V. officinalis or P. methysticum inhibited the intestinal metabolism of midazolam in rats. Conversely, the P-gp-mediated transport of fexofenadine was preferably affected by kava-kava.

Asunto(s)

Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Citocromo P-450 CYP3A , Kava , Midazolam , Extractos Vegetales , Ratas Wistar , Terfenadina , Valeriana , Animales , Valeriana/química , Midazolam/farmacocinética , Midazolam/farmacología , Masculino , Citocromo P-450 CYP3A/metabolismo , Citocromo P-450 CYP3A/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/efectos de los fármacos , Terfenadina/análogos & derivados , Terfenadina/farmacocinética , Humanos , Células CACO-2 , Ratas , Kava/química , Interacciones de Hierba-Droga , Piper/química , Indenos , Pironas , Sesquiterpenos

RESUMEN

The aim of this study was to compare the effects of two anesthetic induction protocols for long procedures carried out in the field in Tapiridae. Sixteen tapirs were divided into two groups (n=8) receiving either detomidine (DET) or dexmedetomidine (DEX) for anesthetic induction. All animals were anesthetized by intramuscular administration of a combination of ketamine (1.5 mg/kg), midazolam (0.2 mg/kg), plus either DET (0.04 mg/kg) or DEX (0.007 mg/kg). Anesthetic maintenance was by continuous infusion of ketamine, midazolam, and glyceryl guaiacol ether at 2 mg/kg per hour, 0.1 mg/kg per hour, and 100 mg/kg per hour, respectively). The animals were kept anesthetized for a total of 50 min to allow physical examination and collection of biological material as part of a research program, and physiological variables (heart rate [HR], respiratory rate, oxyhemoglobin saturation [SpO2], rectal temperature [RT], mean arterial pressure [MAP], blood glucose [GLI], and cortisol) and electrocardiogram were recorded during anesthesia. Anesthetic recovery was monitored by two researchers who were not informed of the induction protocol group. The recorded results were statistically evaluated. In both groups there was an initial increase in MAP, which subsequently decreased; RT gradually decreased during anesthesia; HR and GLI increased throughout the procedure; SpO2 was below normal throughout the procedure. Cortisol levels were significantly higher in the DEX group than in the DET group. Also, the animals in the DEX group had a longer recovery time than those in the DET group. On the basis of the results, we conclude that the combination of alpha-2 agonists and midazolam, ketamine, and glyceryl guaicol ether is an appropriate protocol for the anesthesia of tapirs in the field. However, in moderately extended procedures oxygen supplementation is recommended. Additionally, DEX resulted in fewer cardiovascular effects and longer-lasting sedation than DET.

Asunto(s)

Anestésicos , Dexmedetomidina , Ketamina , Animales , Midazolam/farmacología , Ketamina/farmacología , Dexmedetomidina/farmacología , Hidrocortisona , Anestésicos/farmacología , Éteres , Hipnóticos y Sedantes/farmacología

RESUMEN

BACKGROUND: This study evaluated the anesthetic and cardiorespiratory effects of two anesthetic protocols for salpingectomy or deferentectomy in capuchin monkeys (Sapajus sp). MATERIALS AND METHODS: Five capuchin monkeys (5 per group) received ketamine (20 mg/kg) combined with midazolam (0.5 mg/kg; group KM) or dexmedetomidine (5 µg/kg; group KD) intramuscularly. Anesthesia is induced with propofol intravenously and maintained with isoflurane. Before the start of surgery, fentanyl 3 µg/kg was administered IV, and continuous infusion (10 µg/kg/min) IV was started. Times and quality of anesthetic recovery were evaluated postoperatively. RESULTS: KM and KD resulted in adequate chemical restraint. KD resulted in bradycardia. Intraoperative heart rate and systolic blood pressure were higher in KM than in KD. Both groups had smooth recovery. Time to standing was longer in KM than in KD. CONCLUSION: Both protocols allowed the performance of surgeries, with few cardiorespiratory effects. Anesthetic recovery was smooth and shorter in KD group.

Asunto(s)

Anestésicos , Dexmedetomidina , Isoflurano , Ketamina , Sapajus , Animales , Femenino , Ketamina/farmacología , Isoflurano/efectos adversos , Midazolam/farmacología , Fentanilo/farmacología , Dexmedetomidina/farmacología , Cebus , Salpingectomía

RESUMEN

Introduction: Empathy is a fundamental prosocial behavior. It has been defined as perception, awareness, and understanding of others' emotional states, including painful processes. Mice living in pairs with conspecific chronic suffering from constriction injury exhibit pain hypersensitivity mediated by the amygdaloid complex. Nevertheless, the underlying mechanisms in the amygdala responsible for this response remain to be determined. This study investigated if the anxiolytic benzodiazepine midazolam (MDZ) and cannabidiol (CBD), a phytocannabinoid with multiple molecular targets, would attenuate this behavioral change. We also investigated if serotonergic and γ-aminobutyric acid (GABA)ergic mechanisms in the amygdala are involved in this effect. Materials and Methods: Male Swiss mice were housed in pairs for 28 days. The pairs were divided into two groups on the 14th day: cagemate nerve constriction and cagemate sham. On the 24th day, cagemates underwent a stereotaxic surgery and, on the 28th day, were evaluated on the writhing test. Results: The results showed that living with chronic pain leads to hypernociception in the cagemate and increases the expression of 5-HT3 receptor (5-HT3R) and glutamic acid decarboxylase 67 within the amygdala. MDZ (3.0 and 30 nmol) and CBD (30 and 60 nmol) attenuated the hypernociceptive behavior. The 5-HT3R antagonist ondansetron (0.3 nmol) prevented the antinociceptive effects of MDZ and CBD. Conclusion: These findings indicate that 5-HT3R and GABAergic mechanisms within the amygdala are involved in the pain hypersensitivity induced by the empathy for pain model. They also suggest that MDZ and CBD could be a new potential therapy to alleviate emotional pain disorders.

Asunto(s)

Cannabidiol , Midazolam , Ratones , Masculino , Animales , Midazolam/farmacología , Cannabidiol/farmacología , Serotonina/farmacología , Empatía , Dolor , Amígdala del Cerebelo

RESUMEN

The cardiac evaluation of wild animals is still a wide and largely unknown field for several species. Therefore, through complimentary examinations such as radiography, echocardiography and serum troponin levels, this study aimed at describing the values observed in 12 crab-eating foxes (Cerdocyon thous) anesthetized with a combination of intramuscular ketamine and midazolam. Thus, through complementary exams such as radiography, echocardiography and serum troponin levels, the aim of this study was to describe the cardiac values in 12 wild foxes (C. thous) anesthetized with an intramuscular injection of ketamine and midazolam. After anaesthetization, the radiographic, echocardiographic and immunoenzymatic reference values for the 12 males in the sample group were determined. Compared with those in domestic canids, there was a decrease in the sizes of the septum, wall and left ventricular cavity as well as decreases in the transmitral blood flow velocity indices, correlated with preserved serum cardiac troponin (cTnI) levels. Thus, M-mode echocardiography proved to be safer, with results that were comparative to those for other species of wild canids with indexed values. In addition, when evaluating the systolic function and segmentary contractions, the anesthetic combination did not have any effects on the results of complementary examinations performed in crab-eating foxes (C. thous) included in this study.

Asunto(s)

Canidae , Ketamina , Animales , Brasil , Ecocardiografía/veterinaria , Ketamina/farmacología , Masculino , Midazolam/farmacología , Valores de Referencia , Troponina

RESUMEN

This study aimed to compare the effects of different coinduction agents on the duration and dose of propofol in healthy cats. Six cats aged 4.8 ± 1.0 years and weighing 4.4 ± 1.1 kg participated in 4 treatment groups of propofol combined with: saline or control group (TC); ketamine 2 mg/kg (Tket); fentanyl 1 µg/kg (Tfen); or midazolam 0.3 mg/kg (Tmid). Twenty minutes following premedication with dexmedetomidine at 10 µg/kg, induction followed the same protocol in all groups, starting with a propofol bolus of 1 mg/kg over 1 minute followed by an adjuvant, then propofol again at 1 mg/kg/minute for orotracheal intubation. Variables recorded were (in minutes): time of extubation, time to return of palpebral reflex, eye recentralization, recovery of consciousness, quadrupedal position and total propofol dose used (mg/kg). A comparison between the 4 groups was performed by analysis of variance followed by Dunnett test under 5% significance. There was no significant difference in any of the times evaluated during anesthetic recovery between the groups. The propofol dose used to allow orotracheal intubation was significantly lower in all groups compared to TC (P < .05). Ketamine, midazolam, and fentanyl are indicated as suitable choices for coinduction with propofol in cats.

Asunto(s)

Dexmedetomidina , Ketamina , Propofol , Anestésicos Intravenosos/farmacología , Animales , Gatos , Dexmedetomidina/farmacología , Ketamina/farmacología , Midazolam/farmacología , Propofol/farmacología

RESUMEN

The purpose of this study was to compare the hemodynamic effects of four different combinations of midazolam and opioids in healthy dogs. Twenty-four healthy dogs were divided in four groups (n = 6) using intramuscular midazolam 0.3 mg/kg and morphine 0.3 mg/kg (GMOR), methadone 0.3 mg/kg (GMET), butorphanol 0.2 mg/kg (GBUT) or fentanyl 5 ug/kg (GFEN). Cardiovascular variables were recorded before (TB) and 20 minutes following drug administration (T20) and comprised arterial blood pressure, heart rate and cardiac index. Subsequently, left ventricular work index and total peripheral resistance index were calculated using the previous variables. At the end of the study, data were compared using analysis of variance followed by Tukey test and Friedman followed by Dunn test, all under 5% significance. No differences were found on cardiovascular variables at all times among the groups, which indicates that all combinations provide hemodynamic stability for clinical sedation of healthy dogs. However, a few animals showed paradoxical excitation in GBUT. In conclusion, the association of midazolam with morphine, methadone, butorphanol or fentanyl provides cardiovascular stability and can be used to sedate dogs undergoing cardiovascular examination, although caution is warranted with the use of midazolam with butorphanol due to possible paradoxical excitation.

Asunto(s)

Analgésicos Opioides , Midazolam , Analgésicos Opioides/farmacología , Animales , Butorfanol/farmacología , Perros , Frecuencia Cardíaca , Hemodinámica , Midazolam/farmacología

RESUMEN

BACKGROUND: This study evaluated the cardiopulmonary effects and anaesthetic depth induced by a propofol infusion rate of 0.8 mg/kg/min in monkeys (Sapajus apella). MATERIALS AND METHODS: Five capuchin monkeys received dextroketamine-midazolam intramuscularly. After a maximum duration of 5 min, the values of the physiological parameters were recorded, and a venous catheter was placed. After recovery from chemical restraint, the animals were anaesthetized with propofol intravenously, which was maintained for 1 h. Physiological parameters, anaesthetic depth, the time and quality of anaesthetic recovery were evaluated. RESULTS: Heart and respiratory rates, systolic blood pressure and rectal temperature during propofol infusion were lower than those during anaesthesia induction with dextroketamine-midazolam. Unconsciousness, muscle relaxation and lack of response to tail clamping were observed during propofol infusion. No animals showed excitement or vocalization during anaesthetic recovery. CONCLUSION: Propofol infusion rate of 0.8 mg/kg/min promoted surgical general anaesthesia, with transient hypotension, which showed excellent anaesthetic recovery.

Asunto(s)

Propofol , Anestesia General , Anestésicos Intravenosos/farmacología , Animales , Midazolam/farmacología , Propofol/farmacología , Sapajus apella

RESUMEN

Aim: The purpose of this study was to evaluate the antifungal activity of midazolam, alone and in association with azoles, against isolates of clinical Candida spp. in planktonic and biofilm form. Materials & methods: The antifungal activity was observed using the broth microdilution technique. Flow cytometry tests were performed to investigate the probable mechanism of action and the comet test and cytotoxicity test were applied to evaluate DNA damage. Results: Midazolam (MIDAZ) showed antifungal activity against planktonic cells (125-250 µg/ml) and reduced the viability of Candida spp. biofilms (125 a 2500 µg/ml). The interaction of MIDAZ against Candida spp. biofilms was observed through scanning electron microscopy, causing alteration of their appearance. Therefore, MIDAZ has antifungal potential against Candida spp.

Asunto(s)

Antifúngicos/farmacología , Candida/efectos de los fármacos , Candidiasis/microbiología , Midazolam/farmacología , Biopelículas/efectos de los fármacos , Candida/genética , Candida/crecimiento & desarrollo , Candida/fisiología , Evaluación Preclínica de Medicamentos , Farmacorresistencia Fúngica , Fluconazol/farmacología , Humanos , Pruebas de Sensibilidad Microbiana

RESUMEN

Context: Oral administration of midazolam is one of the most important protocols for producing adequate conscious sedation; however, it has an unpleasant taste and is poorly tolerated by pediatric patients. Aim: The aim of this study was to evaluate the sedative effect of diluted midazolam in different vehicles used to mask its unpleasant taste. Methods and Material: A total of 30 male mice (BALB-c) were randomly distributed in five groups. They were administered diluted midazolam in different vehicles (saline solution, paracetamol syrup, diclofenac suspension, multi-vitamin syrup, and boxed juice). All suspensions were administered orally (0.6 mg/Kg). The pH variation was evaluated with a digital pH meter, and the quality of sedation was evaluated in three tests: hole board test, grip strength test, and forced swimming test. Results: The paracetamol syrup vehicle was found to be the only vehicle which did not change its pH over time after dilution of midazolam. When evaluating the perforated platform, the greatest sedative effect was observed in the midazolam group with the paracetamol syrup (P > 0.05). Regarding grip strength, a difference was evident in all study groups at 45 minutes (P = 0.006); the midazolam group with the multi-vitamin syrup was less effective. Regarding the response time to forced swimming, the midazolam group with the paracetamol syrup presented the longest time at 15 and 30 minutes (5.39 ± 0.93 and 6.29 ± 0.83, respectively). Conclusion: The suspension of midazolam diluted in the paracetamol syrup is the most suitable for performing conscious sedation efficiently.

Asunto(s)

Hipnóticos y Sedantes , Midazolam , Acetaminofén , Administración Oral , Animales , Sedación Consciente , Humanos , Hipnóticos y Sedantes/farmacología , Masculino , Ratones , Midazolam/farmacología

Asunto(s)

Anticonvulsivantes/uso terapéutico , Convulsiones/tratamiento farmacológico , Administración Intranasal , Administración Rectal , Anticonvulsivantes/farmacología , Benzodiazepinas/farmacología , Niño , Diazepam/farmacología , Diazepam/uso terapéutico , Epilepsia/tratamiento farmacológico , Humanos , Midazolam/farmacología , Midazolam/uso terapéutico , Estados Unidos , United States Food and Drug Administration

RESUMEN

BACKGROUND: There is scarce information detailing clinical and physiological effects of reversible injectable protocols of chemical restraint on Neotropical primates. METHODS: Nineteen captive Spix´s Owl monkeys (Aotus vociferans) were assessed in a double-blind randomized crossover study using the following: ketamine/xylazine [KX], ketamine/midazolam [KM] and ketamine/xylazine/midazolam [KXM]. During immobilization, respiratory and pulse rates, rectal temperature, haemoglobin oxygen saturation and arterial blood pressure were recorded at 5-minute intervals during a 20-minute period; afterwards, antagonist drugs (yohimbine for xylazine and flumazenil for midazolam) were, respectively, administered. Quality and duration of induction, immobilization and recovery periods were recorded. RESULTS: Ketamine/xylazine increased manipulation sensitivity and produced poor muscle relaxation. KM maintained all assessed parameters within physiological ranges. KXM produced depressant cardiorespiratory effects and hypotension. All protocols produced hypothermia. CONCLUSIONS: Based on its adequate anaesthetic depth and minimum effects on physiological parameters, KM is suitable for immobilizing A vociferans and performing short-term procedures lasting around 20 minutes.

Asunto(s)

Analgésicos/farmacología , Aotidae/fisiología , Inmovilización/veterinaria , Ketamina/farmacología , Midazolam/farmacología , Xilazina/farmacología , Animales , Estudios Cruzados , Método Doble Ciego , Combinación de Medicamentos , Femenino , Inyecciones Intramusculares/veterinaria , Masculino

RESUMEN

The selective breeding of laboratory rodents with different anxiety-related traits is the subject of growing interest. The present study compared the effects of the benzodiazepine midazolam in the elevated plus maze (EPM) test of anxiety in two lines of Wistar rats that were selectively bred in our laboratory for either high or low anxiety-like traits based on a contextual freezing conditioning paradigm. After phenotyping anxiety-like traits (i.e., conditioned freezing behavior), Carioca High-Freezing [CHF], Carioca Low-Freezing [CLF]) and control rats were intraperitoneally injected (1.0 ml/kg) with .9 % saline or midazolam (.25, .5, .75, and 1.0 mg/kg) and subjected to the EPM 30 min later. After the saline injection, the CHF and CLF groups exhibited lower and higher open-arm exploration in the EPM, respectively, compared with control rats. These results indicate that anxiety-related traits previously selected from an associative learning paradigm can also be phenotypically expressed in an ethologically based animal model of anxiety. All midazolam doses significantly increased open-arm exploration in both CHF and control animals, but this anxiolytic-like effect in CLF rats was only observed at the lowest dose tested (.25 mg/kg). The present findings indicate that these two breeding lines of rats are a useful model for studying anxiety, and the anxiolytic effect of midazolam depends on genetic variability that is associated with basal reactions to threatening situations.

Asunto(s)

Condicionamiento Clásico/efectos de los fármacos , Pérdida de Tono Postural/efectos de los fármacos , Midazolam/farmacología , Animales , Ansiolíticos/farmacología , Relación Dosis-Respuesta a Droga , Aprendizaje por Laberinto , Fenotipo , Ratas Endogámicas , Selección Artificial

RESUMEN

The aim of this prospective, randomized, blinded crossover study was compare the cardiopulmonary and sedative effects of ketamine in combination with acepromazine, diazepam, dexmedetomidine, midazolam or xylazine, injected intramuscularly in rabbits, using eight one-year-old male New Zealand rabbits (4.1 ± 0.40 kg). All treatments included ketamine (K; 30 mg/kg) in combination with one of the following: acepromazine 0.5 mg/kg (treatment KA); diazepam 1 mg/kg (KD); dexmedetomidine 0.025 mg/kg (KDex); midazolam 1 mg/kg (KM); or xylazine 3 mg/kg (KX) mixed in the same syringe and injected intramuscularly. Cardiopulmonary variables, blood gases and sedative scores were measured before injection (T0 or baseline) and every 10 min thereafter, over a 60-min period. There were reductions in heart rate, compared with the baseline, at all evaluation times in treatment KX. Treatments KDex, KM and KX presented reductions in respiratory rate at all evaluation times, in comparison with the baseline. There were reductions in mean arterial pressure in KA and KX at times T10-T60 and in PaO2 in KDex, KM and KX at T10-T50. The sedation scores were similar in KA, KDex, KM and KX at T10-T20. Ketamine in combination with acepromazine, dexmedetomidine, midazolam or xylazine promoted similar sedative effects for twenty minutes, but the α2-agonists can promote hypoxemia.

Asunto(s)

Anestesia/veterinaria , Anestésicos/farmacología , Ketamina/farmacología , Acepromazina/administración & dosificación , Acepromazina/efectos adversos , Acepromazina/farmacología , Periodo de Recuperación de la Anestesia , Animales , Presión Arterial/efectos de los fármacos , Estudios Cruzados , Dexmedetomidina/administración & dosificación , Dexmedetomidina/efectos adversos , Dexmedetomidina/farmacología , Combinación de Medicamentos , Frecuencia Cardíaca/efectos de los fármacos , Hipnóticos y Sedantes , Hipoxia , Inyecciones Intramusculares/veterinaria , Ketamina/administración & dosificación , Ketamina/efectos adversos , Masculino , Midazolam/administración & dosificación , Midazolam/efectos adversos , Midazolam/farmacología , Estudios Prospectivos , Conejos , Frecuencia Respiratoria/efectos de los fármacos , Xilazina/administración & dosificación , Xilazina/efectos adversos , Xilazina/farmacología

RESUMEN

This study aimed to evaluate the applicability of rodent behavioral tests to assess the effects of midazolam and flumazenil in green iguanas. Four tests commonly used to assess sedation in rodents-the open field test, forced swim test, behavioral scale, and traction test-were conducted in 10 juveniles iguanas. The animals received midazolam (2 mg/kg IM) or 0.9% NaCl (0.4 mL/kg IM), and the tests were conducted between 0 and 300 min thereafter. To verify the effects of midazolam and flumazenil, the most informative tests from the evaluation stage and the limb withdrawal latency time (LWLT) were used. All 10 iguanas were tested under 4 conditions, as follows: MS, midazolam (2 mg/kg IM), followed 30 min later by 0.9% NaCl (0.4 mL/kg IM); FS, flumazenil (0.05 mg/kg IM), followed by 0.9% NaCl (0.4 mL/kg IM) 30 min later; MF, midazolam (2 mg/ kg IM), followed by flumazenil (0.05 mg/kg IM) 30 min later; and CON, 0.9% NaCl (0.4 mL/kg IM). The behavioral scale and the forced swim test showed the best detection of the onset, peak effect, and the differences between the sedated and control iguanas, with testing done between 15 and 240 min after drug administration. The sedative effect of midazolam began at 15 min and persisted through 180 min when assessed on the behavioral scale and 240 min when assessed by the forced swim test; flumazenil administration reversed the sedative effect. An increase in the LWLT was observed in the midazolam treatment groups between 15 and 30 min after drug administration. Flumazenil decreased LWLT between 15 and 180 min in the FS and at 60 min in the MF. In conclusion, the best methods to assess sedation in iguanas were the behavioral scale and the forced swim test. A dose of 2 mg/kg of midazolam was effective at inducing sedation in these juvenile iguanas, and this effect could be reversed by flumazenil.

Asunto(s)

Flumazenil/farmacología , Hipnóticos y Sedantes/farmacología , Iguanas , Midazolam/farmacología , Animales , Antídotos/administración & dosificación , Antídotos/farmacología , Femenino , Flumazenil/administración & dosificación , Ciencia de los Animales de Laboratorio , Masculino , Midazolam/administración & dosificación

RESUMEN

OBJECTIVE: Drug-induced sleep endoscopy (DISE) has gained interest for upper airway evaluation in patients with snoring and obstructive sleep apnea (OSA), and different drugs have been used to induce sedation. Nevertheless, all drugs have presented specific advantages and disadvantages with differential effects on respiratory physiology. This study evaluated and compared the effects of midazolam, propofol and dexmedetomidine on DISE findings, O2 nadir, and bispectral index (BIS) in the same sample of patients. STUDY DESIGN: Case series prospective study. METHODS: Consecutive patients who elected to undergo surgery for OSA treatment and were intolerant to conservative therapies underwent DISE with propofol, dexmedetomidine, and midazolam between July 2015 and July 2016. RESULTS: Fifty-two patients were analyzed, and 43 (82.7%) were men. Agreement among drugs for both degree and patterns of obstruction was excellent at all sites (velum, oropharynx, and epiglottis) except for the tongue base. Dexmedetomidine had the least complete collapse sites and highest O2 nadir and was the only drug for which apnea severity and obstruction levels (upper, lower, or combined) were correlated. The variability among drug treatments for the BIS index was considerable, and propofol had the lowest variability and average value. CONCLUSION: Drug selection had a relevant influence in DISE findings. Compared with dexmedetomidine, midazolam and propofol presented higher incidence of tongue base collapse, lower O2 levels, and lower BIS index values. Propofol resulted in an O2 nadir that most resembled that observed during polysomnography. The BIS index variability differed among drugs, and its use was considered relevant for sedation orientation. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:506-513, 2019.

Asunto(s)

Endoscopía/métodos , Hipnóticos y Sedantes/farmacología , Polisomnografía/métodos , Apnea Obstructiva del Sueño/diagnóstico , Sueño/efectos de los fármacos , Adulto , Dexmedetomidina/farmacología , Epiglotis/efectos de los fármacos , Femenino , Humanos , Masculino , Midazolam/farmacología , Persona de Mediana Edad , Nariz/efectos de los fármacos , Orofaringe/efectos de los fármacos , Propofol/farmacología , Estudios Prospectivos , Lengua/efectos de los fármacos , Adulto Joven

RESUMEN

This study was done to determine the time while the binary admixtures with midazolam and haloperidol drugs are administered by perfusion to the patients in the clinical routine. Samples with different concentrations of both drugs were prepared following the usual clinical practice. Solvents used were 0.9 % sodium chloride solution and 5% dextrose, and viaflo plastic bags were used as the containers of the admixtures. Samples were not protected from light and were stored at 20 ºC or at 4 ºC. Compatibility and physicochemical stability were studied by visual inspection, turbidity measurement, pH determination and ultraviolet detection high performance liquid chromatography (UV-HPLC) was used to determine midazolam and haloperidol concentrations. The assay was validated following the FDA and EMA guidelines. Darunavir was used as internal standard (IS). For the studied admixtures, turbidity measurements and pH determinations showed little changes in function of the time. Haloperidol and midazolam concentrations determined by HPLC are within the acceptable range of drug concentrations, which are considered stable for four days in case of admixtures stored at 20 ºC and for seven days for refrigerated admixtures. Taking into account the microbiological risk matrix, the compatibility and the chemical and microbiological stability of the midazolam and haloperidol in the co-administered admixtures in viaflo plastic bags with 0.9 % sodium chloride solution and 5% dextrose can be set as 48 hours when samples are stored at 20 ºC and one week if they are refrigerated.

Asunto(s)

Midazolam/farmacología , Haloperidol/farmacología , Cromatografía Líquida de Alta Presión/métodos , Hipnóticos y Sedantes/administración & dosificación

RESUMEN

Introduction: Drug-drug interactions occur more frequently in intensive care units than in other services. However, in Colombia, there are few studies on this problem in critically ill patients. Objectives: To characterize potential drug-drug interactions generated from prescriptions during hospitalization in an intensive care unit and to determine factors associated with their onset. Materials and methods: A retrospective cohort was assembled with patients hospitalized in an intensive care unit for a seven-month period. The daily prescription was assessed for potential drugdrug interactions using the Lexicomp® program. We calculated the incidence of interactions, classified them by type, severity, and level of documentation, and evaluated the factors associated with their onset using logistic regression. Results: The proportion of patients with at least one interaction was 84% while 87% had more than one interaction; the median was six interactions per patient. The most frequent was fentanyl and midazolam (23%). Moderate interactions were the most frequent by severity (77.6%) and by documentation (52.6%). The most common index and precipitating drugs were midazolam (12%) and fentanyl (10.6%), respectively. Age (OR=3.1) and the number of drugs (OR=11.8) were associated with the occurrence of interactions. Conclusions: Given their high frequency and potential negative impact, the systematic monitoring of prescriptions in intensive care units to detect interactions is important. Such monitoring contributes to the rational use of medicines and to improve the quality of care.

Asunto(s)

Interacciones Farmacológicas , Centros de Atención Terciaria/estadística & datos numéricos , Adolescente , Adulto , Anciano , Colombia , Enoxaparina/efectos adversos , Enoxaparina/farmacología , Femenino , Fentanilo/efectos adversos , Fentanilo/farmacología , Humanos , Incidencia , Unidades de Cuidados Intensivos/estadística & datos numéricos , Masculino , Midazolam/efectos adversos , Midazolam/farmacología , Persona de Mediana Edad , Cloruro de Potasio/efectos adversos , Cloruro de Potasio/farmacología , Estudios Retrospectivos , Adulto Joven

RESUMEN

Resumen Introducción. Las interacciones farmacológicas ocurren con mayor frecuencia en las unidades de cuidados intensivos que en otros servicios. Sin embargo, en Colombia son pocos los estudios en que se han evaluado en pacientes críticamente enfermos. Objetivos. Caracterizar las potenciales interacciones farmacológicas en las prescripciones de pacientes hospitalizados en una unidad de cuidados intensivos y determinar los factores asociados con su aparición. Materiales y métodos. Se analizó una cohorte retrospectiva de pacientes hospitalizados en una unidad de cuidados intensivos, durante un periodo de siete meses. Las prescripciones diarias se evaluaron en busca de potenciales interacciones farmacológicas mediante el programa Lexicomp™. Se calculó la incidencia de interacciones, se clasificaron según su tipo, gravedad y grado de documentación, y se evaluaron los factores asociados con su aparición mediante regresión logística. Resultados. La proporción de pacientes con por lo menos una interacción fue de 84 %, en tanto que el 87 % presentó más de una interacción; la mediana fue de seis interacciones por paciente. La más frecuente fue entre el fentanilo y el midazolam (23 %). Las interacciones de gravedad y grado de documentación moderados fueron las más frecuentes (77,6 y 52,6 %, respectivamente). El fármaco índice más frecuente fue el midazolam (12 %) y el precipitante más frecuente, el fentanilo (10,6 %). La edad (odds ratio, OR=3,1) y el número de medicamentos (OR=11,8), se asociaron con la aparición de interacciones. Conclusiones. Dada su elevada frecuencia y potencial impacto negativo es importante vigilar sistemáticamente las prescripciones en cuidados intensivos para detectar las interacciones, con el fin de contribuir al uso racional de los medicamentos y a mejorar la calidad de la atención.

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Abstract Introduction: Drug-drug interactions occur more frequently in intensive care units than in other services. However, in Colombia, there are few studies on this problem in critically ill patients. Objectives: To characterize potential drug-drug interactions generated from prescriptions during hospitalization in an intensive care unit and to determine factors associated with their onset. Materials and methods: A retrospective cohort was assembled with patients hospitalized in an intensive care unit for a seven-month period. The daily prescription was assessed for potential drugdrug interactions using the Lexicomp® program. We calculated the incidence of interactions, classified them by type, severity, and level of documentation, and evaluated the factors associated with their onset using logistic regression. Results: The proportion of patients with at least one interaction was 84% while 87% had more than one interaction; the median was six interactions per patient. The most frequent was fentanyl and midazolam (23%). Moderate interactions were the most frequent by severity (77.6%) and by documentation (52.6%). The most common index and precipitating drugs were midazolam (12%) and fentanyl (10.6%), respectively. Age (OR=3.1) and the number of drugs (OR=11.8) were associated with the occurrence of interactions. Conclusions: Given their high frequency and potential negative impact, the systematic monitoring of prescriptions in intensive care units to detect interactions is important. Such monitoring contributes to the rational use of medicines and to improve the quality of care.

Asunto(s)

Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Interacciones Farmacológicas , Centros de Atención Terciaria/estadística & datos numéricos , Cloruro de Potasio/efectos adversos , Cloruro de Potasio/farmacología , Midazolam/efectos adversos , Midazolam/farmacología , Fentanilo/efectos adversos , Fentanilo/farmacología , Incidencia , Estudios Retrospectivos , Colombia , Enoxaparina/efectos adversos , Enoxaparina/farmacología , Unidades de Cuidados Intensivos/estadística & datos numéricos

RESUMEN

To evaluate the apoptosis in parotid glands of rats treated with midazolam associated or not with pilocarpine, 60 Wistar rats were assigned to 6 groups: control groups received saline solution for 30 days (S30) and 60 days (S60) and the other groups received pilocarpine for 60 days (P60), midazolam for 30 days (M30), midazolam for 30 days and 30 days of saline (M30 + S30), and finally midazolam for 30 days and 30 days of midazolam and pilocarpine (M30 + MP30). Histological sections were subjected to the TdT-mediated dUTP-biotin nick and labeling technique. The number of positive and negative cells was quantified, calculating the apoptotic index. ANOVA at 2 criteria and Tukey's test were used. A greater apoptotic index was observed in the M30 (52.79 ± 9.01) and M30 + S30 (62.43 ± 8.52) groups when compared with the S30 (37.94 ± 5.94) and S60 (31.85 ± 9.18) groups, respectively (p < 0.05). There was no difference between M30 + MP30 (30.98 ± 6.19) and S60 (31.85 ± 9.18) groups regarding apoptotic index. Chronic administration of midazolam has been shown to increase the number of apoptotic cells in the parotid glands of rats. However, pilocarpine inhibited this effect, thus inhibiting the apoptosis.

Asunto(s)

Apoptosis/efectos de los fármacos , Midazolam/farmacología , Pilocarpina/farmacología , Glándulas Salivales/citología , Glándulas Salivales/efectos de los fármacos , Animales , Masculino , Ratas , Ratas Wistar