Remifentanil target-controlled infusion with intranasal dexmedetomidine for vitreoretinal procedures: a randomized controlled trial

AimTo evaluate the consumption of remifentanil (as a primary end-point), analgesia, sedation, hemodynamics, respiratory effects, and surgeon and patient satisfaction (as a secondary end-point) with dexmedetomidine sedation compared with those of remifentanil sedation in patients undergoing vitreoretinal surgery.MethodsPatients subjected to retinal ophthalmic surgical procedures were randomized to one of two intraoperative sedation groups: one group (n = 21) received intranasal dexmedetomidine plus intravenous remifentanil (DEX-REMI group), and the other group (n = 19) received intravenous remifentanil only (REM group). The treatment was placebo-controlled. The sedation level was controlled according to the bispectral index, with target values between 80%-90%. Patient levels of comfort, sedation, and pain were documented. The number of intraoperative complications and the level of satisfaction were assessed. Remifentanil consumption and hemodynamic parameters were also included in the statistical analysis.ResultsThe level of remifentanil consumption was significantly lower in the DEX-REMI group, but combination sedation improved the surgeon''s, anesthesiologist''s, and patients'' satisfaction scores. Importantly, the number of complications was zero in the DEX-REMI group, while eight cases of complications were noted in the REM group. The DEX-REMI group showed lower mean minimal arterial pressure, but it was still in the normotensive range.ConclusionsFor patients undergoing ophthalmic procedures, sedation with a combination of intranasal dexmedetomidine and an intravenous infusion of remifentanil provides lower remifentanil consumption, better satisfaction scores, and a lower complication rate than sedation with a remifentanil infusion alone.Clinical trial number{"type":"clinical-trial","attrs":{"text":"NCT 03251222","term_id":"NCT03251222"}}NCT 03251222

Conscious sedation is an established anesthetic method of choice in patients undergoing short ophthalmic procedures and has been used successfully for many years. In Slovenia, there is also a published protocol in use for such cases (1).Intravenous (i.v.) remifentanil is used for analgesic and sedative purposes. It is a short-acting opioid analgesic with partial anxiolytic action that has been thoroughly studied in obstetric analgesia (2).The fine intra-ocular endoscopic technique is implemented in vitrectomies. Surgical instruments are inserted into the vitreous humor through the sclera by a surgeon. Patient cooperation is crucial during the procedure, meaning the level of sedation should not be too deep. Otherwise, sudden eye movements could potentially result in eye injury (3). For many ophthalmic surgeons, local anesthesia (LA) has become preferred over general anesthesia (GA) because of quicker patient rehabilitation and avoidance of possible complications from GA (4). Several methods of LA have been described for vitreoretinal cases, including retrobulbar, peribulbar, sub-Tenon’s, and even topical anesthesia (5). Many drugs have been used for sedation during eye surgery, such as propofol, benzodiazepines, and opioids, and there is a relative risk of oversedation, disorientation, and confusion, in addition to an increased risk of respiratory depression and oxygen desaturation (5,6). All of these adverse effects can hamper patient cooperation during surgery and make these agents less than ideal for intraoperative management of sedation. As a result, sedatives and anxiolytics with unpredictable dose requirements, such as propofol and midazolam, are not optimal for such procedures.In contrast, dexmedetomidine is a highly selective alpha-2-adrenoreceptor agonist with both sedative and analgesic properties and is not associated with respiratory depressant effects. Dexmedetomidine has been studied for its sedation- and analgesia-sparing properties in intensive care and surgical settings (eg, neurosurgery, maxillofacial surgery, ENT surgery) but not in vitreoretinal surgery (7-9).Dexmedetomidine is mainly administered intravenously. Although intranasal (i.n.) dexmedetomidine is still used off-label, recently an increasing consensus has emerged for its different uses, namely, in non-painful diagnostic procedures, in painful procedures, and in surgical premedication. Some studies have been published regarding this form of use in the pediatric population (10-12). However, at present, there is no consensus regarding indications, dosage, and timing for administration. Available pediatric evidence confirms the efficacy and safety of dexmedetomidine for i.n. administration. The reported dose for pediatric procedures performed under sedation ranges from 2.5 to 4 μg/kg i.n. Onset of action is expected to be slower (25-30-minute) with low doses (1-2 μg/kg) and faster (16.7-28-minute) with higher doses (2.5-3 μg/kg), while offset time is similar in both – 85-minute in average; range 55-100 minutes (13).The aim of our study was to evaluate the consumption of remifentanil (as a primary end-point), analgesia, sedation, hemodynamics, respiratory effects, and surgeon''s and patients'' satisfaction (as a secondary end-point) with dexmedetomidine sedation compared with those of remifentanil sedation in patients undergoing vitreoretinal surgery. We conducted an applied research study that produced objective indicators, showing which type of sedation was more comfortable for patients and more effective in terms of achieving the desired sedation and reducing pain during vitreoretinal procedures with fewer side effects.     

Subinvolution of placental bed vessels: case report and review of the literature

Subinvolution of placental bed vessels, a well-recognized cause of postpartum and postabortal hemorrhage, is defined with prolonged or excessive uterine hemorrhage beginning after the delivery or abortion. Although physiological changes in uteroplacental parts of spiral arteries are well known, the sequence of events in involution of these vessels is not yet clearly understood. In this article we present two cases of subinvolution of placental bed vessels in which we were able to demonstrate the presence of extravillous trophoblast in and around the placental bed vessels. The disease is supposed to be the result of abnormal interaction between maternal uterine cells and fetal trophoblast.     

The role of genital pathogens in morbidity following diathermy loop excision of the transformation zone of the uterine cervix

ObjectiveTo evaluate the role of genital pathogens in postoperative morbidity following diathermy loop excision of the transformation zone (LETZ) of the uterine cervix.MethodsPatients with cervical intraepithelial neoplasia (CIN) who underwent diathermy LETZ were included in a prospective study. Cervical swabs for genital pathogens were collected before the diathermy procedure. After surgery, women were followed-up regarding the occurrence and severity of postoperative pain, bleeding, and discharge.ResultsGenital pathogens were present in 463 of 788 (58.8%) cases. The most frequently isolated groups of microorganisms were group B β-hemolytic Streptococcus, α-hemolytic Streptococcus, Enterococcus species, and coliforms. In patients with genital pathogens, postoperative pain was present in 298 (37.8%), discharge in 262 (33.2%), and bleeding in 236 (29.9%) cases. In patients without genital pathogens, 199 (25.3%) experienced pain, 181 (23.0%) discharge, and 143 (18.1%) bleeding. The differences between the 2 groups were not statistically significant (χ² for pain = 0.675; χ² for discharge = 0.031; χ² for bleeding = 3.444; P > 0.05).ConclusionGenital pathogens are very common among patients with CIN and do not affect the occurrence or severity of pain, discharge, or postoperative bleeding after diathermy LETZ.     

Interactions of metal ions with DNA, its constituents and derivatives, which may be relevant for anticancer research

In this review several types of interactions between metal ions and DNA are given, starting from basic binding to the use of metal complexes in cancer treatment and diagnostics. Metal cations help to neutralize the negative charge of DNA and thus enable the normal functions of DNA but many other interactions are also possible and are discussed in this paper. Various consequences of such interactions can be reversible (e. g. conformational changes) or irreversible (e. g. cleavage). It is known that some metal ions can also damage DNA which can provoke mutations and in some cases leads to cancer. It is clear that we know a lot about metal-DNA interactions but much more information is needed to understand the role of metal ions completely and to use this knowledge successfully.     

Correlation of in vitro and in vivo paracetamol availability from layered excipient suppositories.

An in vivo investigation of paracetamol availability was carried out on eight healthy volunteers, comparing two paracetamol suppository formulations prepared using two different gliceride bases, a fast drug-releasing one and a slow drug-releasing one, i.e. Witepsol H15 and W35, respectively. The formulations were selected on the basis of a previous in vitro drug release study, which showed that, by superimposing the excipients in two layers within the same suppository, the drug release kinetics could be modulated using different ratios between the two layers. The comparison between the two different formulations in terms of plasma profiles and total amounts of drug excreted in urine revealed an increase in the extent of drug absorption from the layered excipient suppository. As the W35 has a higher monoglyceride content than the H15, this improved paracetamol availability could be ascribed to the absorption-enhancing effect of the monoglycerides. Moreover, the W35 has also a higher viscosity, which could possibly cause the suppository to be retained for a longer time in the lower part of the rectum, where the blood is drained directly to the systemic circulation. It was therefore hypothesized that the enhanced paracetamol availability could be also due to a liver bypass mechanism. For a further examination of the paracetamol absorption kinetics after rectal administration, a one-compartment model was fitted to the drug plasma concentration data. This approach allowed to draw absorption versus time profiles, which showed that a retardation actually occurred in paracetamol absorption when using suppositories containing the slow drug releasing excipient W35. These absorption data were then employed for an A level in vitro-in vivo correlation testing, and a linear relationship was found between in vitro release rate and in vivo absorption rate, both for fast releasing and for the layered excipient suppositories.     

Correlates of knee anterior laxity in sportswomen

The purpose of this study was to evaluate whether any of the following factors are related to knee anterior laxity in healthy sportswomen: anthropometric characteristics, lower limb alignment characteristics, hormone-related factors and sport history. Six hundred and sixteen sportswomen were tested in the pre-season. The data have been analysed using linear regression for possible association of knee anterior laxity with other variables. Univariate linear regression indicated a positive association of knee anterior laxity with knee extension and navicular drop and a negative association with body height. Multivariate linear regression analysis showed statistically significant associations between knee anterior laxity and the combination of passive knee extension and the chosen sport (R² = 0.089; p < 0.05). The combination of passive knee extension and sport type was found to be related to the amount of knee anterior laxity, although the association was weak with this combination of factors able to explain only about 9% of the variability in laxity. Knowing which factors influence the amount of knee anterior laxity will help us to better interpret the results of knee anterior laxity testing and help us to understand the possible role of knee anterior laxity as a risk factor for knee injury.     

Preparation in high-shear mixer of sustained-release pellets by melt pelletisation

The preparation of sustained-release pellets by melt pelletisation was investigated in a 10-l high shear mixer and ternary mixtures containing stearic acid as a melting binder, anhydrous lactose as a filler and theophylline as a model drug. A translated Doehlert matrix was applied for the optimisation of process variables and quality control of pellets characteristics. After determination of size distribution, the pellets were characterised with scanning electron microscopy, X-ray photoelectron spectroscopy and porosimetric analysis. Finally, the in vitro release from every single size fraction was evaluated and the release mechanism was analysed. Since the drug release rate decreased when enhancing the pellet size fraction, the 2000-microm fraction, exhibiting a substantially zero-order release, was selected for further in vivo biovailability studies. These data demonstrated that pellets based on the combination of stearic acid and lactose can be used to formulate sustained release pellets for theophylline.     

Pathways of paracetamol absorption from layered excipient suppositories: artificial intelligence approach.

When studying paracetamol availability after rectal administration, the differences between slower and faster release suppositories were discovered. Approach with modelling and simulation of compartment-based models was used to explore the differences. A study of paracetamol from layered excipient suppositories shows that many different mechanisms are involved in the drug pharmacokinetics. There is also a large number of articles, each dealing with only one or with a few of the mechanisms. However, there is little information available on how the mechanisms interact in the organism and thus govern the pharmacokinetics of the drug, which means that systemic view in the expert knowledge is missing. In the case of paracetamol rectal availability the use of partially fuzzyfied model allowed systemic combination of all described mechanisms found in the literature and measured data. In spite of non-identifiability, the model showed that patterns that explained differences in bioavailabilities of the two formulations of suppositories could be found. Results of modelling and simulation show that "in vivo" there is practically no difference in cumulative release profiles between the two formulations. However, due to higher content of mono-di-glycerides in a slower release formulation, the extent of absorption is augmented both by absorption-enhancing effect of mono-di-glycerides and the liver bypass mechanism via diminished viscosity.