Comparison of palonosetron with combined palonosetron and midazolam for preventing postoperative nausea and vomiting after laparoscopic cholecystectomy.

BACKGROUND: Postoperative nausea and vomiting (PONV) is an undesirable complication in patients undergoing general anesthesia. Combination therapy via different mechanisms of action for antiemetic prophylaxis has been warranted for effective treatment of PONV. This study was designed to compare the prophylactic antiemetic effect between midazolam combined with palonosetron (group MP) and palonosetron alone (group P) after laparoscopic cholecystectomy surgeries. METHODS: A prospective randomized controlled trial was investigated in non-smoking female. Eighty-eight patients were randomly divided into 2 groups with 44 patients each. Group MP received 0.05 mg/kg of midazolam intravenously before induction of anesthesia whereas group P received the same volume of normal saline. Immediately after anesthetic induction, 0.075 mg of palonosetron was administered to both the groups. The incidence and severity of PONV were assessed during 2 time intervals (0-2 hours, 2-24 hours), postoperatively. RESULTS: The incidence of PONV during 24 hours after surgery was lower in group MP as compared to group P. There was also a significant difference in the use of rescue antiemetics. The severity of nausea was significantly lower in group MP as compared to group P, in the initial 2 hours after surgery. The incidence of side effects was similar between the 2 groups. CONCLUSION: In the prevention of PONV, midazolam combined with palonosetron, administered during induction of anesthesia was more effective as compared to palonosetron alone.

A study comparing the effect of premedication with intravenous midazolam or dexmedetomidine on ketamine-fentanyl sedoanalgesia in burn patients: A randomized clinical trial.

INTRODUCTION: Dressing changes and wound care-debridement procedures often cause fear and anxiety in burn patients, as these processes are quite painful. In order to determine the best method for alleviating pain during these procedures, the current study compared the efficacy and safety of intravenous dexmedetomidine and midazolam for premedication prior to these painful burn care procedures. METHODS: This comparative and randomized study included patients who had a burn size of 1563%, were aged 1870 years, were diagnosed with the American Society of Anesthesiologists physical status (ASA I-II), and who underwent painful burn care procedures. Patients were intravenously administered either 1 mcg/kg dexmedetomidine (Group 1) or 0.03 mg/kg midazolam (Group 2) prior to the burn care procedure. Recorded at predetermined time points for each patient were heart rhythm (HR), mean arterial pressure (MAP), peripheral oxygen saturation (SpO2), standard bispectral index (BIS), and Ramsay Sedation Scale (RSS). RESULTS: In the dexmedetomidine group, HR and MAP measurements of patients ​​at the 3rd, 5th, and 10th mins during sedation were significantly lower than the baseline values (p < 0.05). A significant decrease in SpO2 was observed in both groups at the 10th min during sedation, but the decline was higher in the midazolam group (p < 0.05). BIS measurements of the patients in both groups were significantly lower at 10 min. during sedation and at 15th and 60th mins during the procedure (p < 0.05). However, there was no significant difference between the group (p > 0.05). The RSS scales of both groups in during the sedation were higher in the 3rd, 5th and 10th mins than the baseline values (p < 0.05), but there was no significant difference between the groups (p > 0.05). The RSS scales of groups in during the burn procedure were significantly higher at 15 th min than the 0 th values, while the RSS scales of both groups were significantly lower in the 45th and 60th mins (p < 0.05). CONCLUSION: Results of this study indicate that dexmedetomidine causes hemodynamic alterations while midazolam causes respiratory depression. However, these effects are not severe, and we conclude that both agents are safe and effective to ensure sedation prior to painful burn-care procedures.

A nurse-driven analgesia and sedation protocol reduces length of PICU stay and cumulative dose of benzodiazepines after corrective surgery for tetralogy of Fallot.

PURPOSE: Analgesia and sedation protocols are reported to reduce the requirement of sedative and analgesic agents, duration of mechanical ventilation, and length of pediatric intensive care unit (PICU) stay. However, these studies often were conducted based on inhomogeneous cohorts. The aim of this study was the evaluation of a nurse-driven analgesia and sedation protocol in a homogenous population of infants following corrective surgery for tetralogy of Fallot (TOF). DESIGN AND METHODS: This retrospective analysis was conducted in a cardiac PICU of a tertiary referral center. Two cohorts of patients who underwent corrective surgery for TOF below the age of 7 months, were retrospectively evaluated before and after implementation of a nurse-driven analgesia and sedation protocol. We compared peak and cumulative doses of midazolam, morphine, and clonidine, length of PICU stay and time on mechanical ventilation. RESULTS: A total of 33 patients were included in the preimplementation period and 32 during the postimplementation period. Implementation of the nurse-driven analgesia and sedation protocol had no effect on time on mechanical ventilation (72 hr [24-141] vs. 49 hr [24-98]), but significantly on length of PICU stay (7 days [5-14] vs. 5 days [4-7]). Cumulative doses of midazolam (7.37 mg/kg [4.70-17.65] vs. 5.0 mg/kg [2.70-9.12]) as well as peak doses of midazolam (0.22 mg·kg-1 ·hr-1 [0.20-0.33] vs. 0.15 mg·kg-1 ·hr-1 [0.13-0.20]) and morphine (50.0 µg·kg-1 ·hr-1 [39.7-79.9] vs. 42.5 µg·kg-1 ·hr-1 [29.7-51.8]) were significantly reduced. The postimplemantation group showed no increase in postoperative complications and adverse events. PRACTICE IMPLICATIONS: The implementation of a nurse-driven analgesia and sedation protocol is safe in infants following corrective surgery for TOF. It reduces significantly the length of PICU stay, cumulative and peak doses of midazolam and peak doses of morphine.

Implementation of Intranasal Midazolam for Prolonged Seizures in a Child Neurology Practice.

Currently, evidence supports the use of intranasal midazolam as an effective, and in many cases, preferable treatment option for prolonged seizures in children. Despite this knowledge, intranasal midazolam is not routinely found as a standard of care. The goal of this project was to implement the use of intranasal midazolam as a rescue medication for prolonged seizures within a child neurology practice and, in doing so, create a model for implementation that would be replicable for other practice sites. This project focused on the development of a process to make intranasal midazolam available as a treatment option and then the creation of an educational intervention for providers within a child neurology practice. Provider surveys analyzed provider attitudes toward intranasal midazolam and its frequency of use. Because of this project, a dramatic increase in the prescribing of intranasal midazolam was observed within a child neurology practice.

Comparison of blood microsampling with DBS and conventional blood collection techniques used in a midazolam biostudy.

BACKGROUND: Quantitative DBS LC-MS/MS assay for midazolam was used to compare two sample collection techniques (venipuncture and finger prick) and the midazolam concentrations measured in plasma samples, DBS and dried plasma spots. METHODOLOGY: Midazolam was extracted from DBS cards and compared with whole blood collected from usual venipuncture. Dried plasma spots were also compared with plasma. The blood volume used as well as the temperature impact during the blood and plasma deposits was evaluated. Midazolam was administrated to six healthy subjects during a clinical trial to obtained blood and plasma samples for the statistical comparison. CONCLUSION: The method for midazolam using DBS was validated and showed an excellent performance. Excellent correlations were observed when the same collection procedures were used.

Padronização da anestesia em suínos para procedimentos cirúrgicos cardiovasculares experimentais / Standardization of anesthesia in swine for experimental cardiovascular surgeries / Estandarización de la anestesia en cerdos para procedimientos quirúrgicos cardiovasculares experimentales

JUSTIFICATIVA E OBJETIVO: Embora sejam os cães os animais mais utilizados em Cirurgia Experimental, nota-se crescente utilização de ovinos, bovinos e suínos como modelos para experimentação científica. Assim, faz-se necessário maior aprendizado de seu tratamento e padronizações básicas para os procedimentos cirúrgicos mais complexos em suínos. O objetivo foi avaliar a sedação e analgesia, obtidas pela injeção intramuscular de midazolam e cetamina e anestesia local com lidocaína a 2 por cento sem vasoconstritor, na realização de traqueostomia, dissecção de artéria e veia femorais. MÉTODO: A freqüência cardíaca e o reflexo córneo-palpebral foram avaliados logo no início da sedação, durante os procedimentos cirúrgicos descritos e após seu término. Foram utilizados oito suínos fornecidos por fazendas locais sem tratamento prévio da raça Large White, com peso de 35 a 42 quilos que receberam injeção intramuscular de 22 mg.kg-1 de cetamina e 0,3 mg.kg-1 de midazolam. RESULTADOS: A abordagem anestésica nesses animais, de difíceis intubação e acesso aos vasos profundos, provou ser segura para sedação e analgesia através do método utilizado: acesso intramuscular. CONCLUSÃO: Obteve-se adequado plano de anestesia para o procedimento proposto.

BACKGROUND AND OBJECTIVES: Although dogs are the animals used more often in Experimental Surgeries, the use of sheep, bovine, and swine as models for scientific experiments has been growing. Thus, further learning on the treatment and basic standardization of more complex surgeries in swine are necessary. The objective of this study was to evaluate sedation and analgesia, obtained by the intramuscular administration of midazolam and ketamine, and local anesthetics with 2 percent lidocaine without vasoconstrictor, in tracheostomy and dissection of femoral artery and vein. METHODS: The heart rate and corneal-palpebral reflex were evaluated at the beginning of sedation, during the surgical procedures, and at the end of those procedures. Eight Large White swine, without prior treatment, weighing 35 to 42 kg were provided by local farms. They received intramuscular injections of 22 mg.kg-1 of ketamine and 0.3 mg.kg-1 of midazolam. RESULTS: The anesthetic approach on those animals, who present both difficult intubation and access to deep vessels, proved to be safe for sedation and analgesia by the method chosen: intramuscular administration. CONCLUSIONS: An adequate plane of anesthesia for the proposed procedure was achieved.

JUSTIFICATIVA Y OBJETIVOS: Aunque los perros sean los animales más a menudo usados en Cirugía Experimental, se nota un aumento en la utilización de los ovinos, bovinos y porcinos como modelo para experimentación científica. De esa forma, se hace necesario aprender más con su tratamiento y estandarizaciones básicas para los procedimientos quirúrgicos más complejos en porcinos. El objetivo fue evaluar la sedación y la analgesia obtenidas por la inyección intramuscular de midazolán y la cetamina y anestesia local con lidocaína a un 2 por ciento sin vasoconstrictor, en la realización de traqueostomía, disección de arteria y vena femorales. MÉTODO: La frecuencia cardíaca y el reflejo córneo-palpebral fueron evaluados inmediatamente al inicio de la sedación, durante los procedimientos quirúrgicos descritos y después en su conclusión. Se utilizaron ocho porcinos que fueron suministrados por haciendas de la región sin tratamiento previo de la raza Large White, con peso de 35 a 42 kilos que recibieron inyección intramuscular de 22 mg.kg-1 de cetamina y 0.3 mg.kg-1 de midazolán. RESULTADOS: El abordaje anestésico en esos animales, de difícil intubación y acceso a los vasos profundos, demostró ser seguro para la sedación y analgesia a través del método utilizado: el acceso intramuscular. CONCLUSIÓN: Se obtuvo un adecuado plan de anestesia para el procedimiento propuesto.

Quantitative correlations among CYP3A sensitive substrates and inhibitors: literature analysis.

As a follow-up to the new classification of CYP3A inhibitors, the present work was undertaken to search for quantitative correlations of AUC ratios between sensitive substrates and midazolam (reference). A large set of clinical studies was obtained utilizing the M&T Drug Interaction Database, and recent Product Labels. Linear relationships were found between midazolam and four CYP3A substrates: simvastatin, buspirone, triazolam and eplerenone. Simvastatin and buspirone were consistently more sensitive than midazolam, independent of the inhibitor. Quantitative correlations of AUC ratios between four CYP3A inhibitors (fluconazole, erythromycin, verapamil, diltiazem) and ketoconazole (400 mg/day) were also uncovered. The average potencies of these inhibitors relative to ketoconazole were 27% for erythromycin, 17% for fluconazole and 19% for verapamil.

Reversed-phase ion-pair HPLC method for the direct analysis of 1-OH midazolam glucuronide in human serum.

In recent years, it has become clear that the presence of high concentrations of 1-OH midazolam glucuronide is probably the cause of unexplained prolonged midazolam comas in patients with poor renal function. Until recently, only indirect methods for the analysis of this glucuronide were known, which had several disadvantages, such as a long analysis period (>6 hours). This article describes the validation of a method for the direct analysis of this compound in human serum, using reversed-phase ion-pair high-performance liquid chromatography (HPLC) in combination with solid phase extraction. The intraday and interday coefficients of variation have values below 6% for different possible serum concentrations. The limit of quantification (0.1 mg/L) is much lower than concentrations found in patients with a coma caused by the accumulation of 1-OH midazolam glucuronide. Recovery of 1-OH midazolam glucuronide is almost 100% at three different serum concentrations. Linearity is confirmed for normal serum levels (<1 mg/L) and for serum levels that might occur in patients with impaired renal function (<20 mg/L). Detection is performed at 254 nm with a diode array detector, which can also be used to check the peak purity in case of unexpected impurities.

Comparison of two techniques of narcotic-induced anesthesia for use during recording of magnetic motor evoked potentials in dogs.

OBJECTIVE: To compare 2 types of narcotic-induced anesthesia for recording of transcranial magnetic motor evoked potentials (TMMEP) in dogs. DESIGN: The effect of different doses of sufentanil and midazolam and of sufentanil and nitrous oxide on onset latencies and peak-to-peak, amplitudes of TMMEP was evaluated and compared. ANIMALS: 18 neurologically normal dogs. PROCEDURE: Premedication with droperidol and fentanyl. Induction and maintenance of anesthesia either with sufentanil and midazolam or with sufentanil and nitrous oxide. Recording of TMMEP from the extensor carpi radialis muscle of the forelimb and from the cranial tibial muscle of the hind limb. RESULTS: Both types of narcotic anesthesia induced dose-dependent suppression of TMMEP; compared with baseline recordings, latencies increased, amplitudes decreased, and reproducibility became poorer with increasing dose of the anesthetics. Using surgical-depth doses of the anesthetics, TMMEP could still be recorded in all dogs with sufentanil and nitrous oxide, but not with sufentanil and midazolam anesthesia. CONCLUSIONS: Sufentanil and nitrous oxide anesthesia was superior to sufentanil and midazolam anesthesia for TMMEP recording. CLINICAL RELEVANCE: In small animal medicine, and in dogs in particular, spinal cord diseases are among the most frequently encountered neurologic disorders. The development of techniques for recording TMMEP in anesthetized dogs allows noninvasive evaluation of transmission along descending motor pathways of the spinal cord.