Halogenated anesthetics vs intravenous hypnotics for short and long term sedation in the intensive care unit: A meta-analysis / Anestésicos halogenados vs. hipnóticos intravenosos para sedación a corto y largo plazo en la unidad de cuidados intensivos: un metaanálisis

Objective To comprehensively assess peer-reviewed studies using volatile (VA) or intravenous (i/v) anesthetics for sedation in intensive care units (ICUs), with the hypothesis that the type of sedation may have an impact on survival and other clinically relevant outcomes. Design Systematic review and meta-analysis of randomized and non-randomized trials. Setting ICUs. Participants Critically ill and postoperative patients. Interventions None. Measurements and main results Studies comparing VA versus i/v anesthetics used in the ICU settings were independently systematically searched. Finally, 15 studies (1520 patients of predominantly surgical profile needed VA sedation for less than 96h) were included. VA had no impact on all-cause mortality (very low quality of evidence, Odds Ratio=0.82 [0.60–1.12], p=0.20). However, VA were associated with a reduction in duration of mechanical ventilation (p=0.03) and increase in ventilator-free days (p<0.001). VA also reduced postoperative levels of cardiac troponin (24h), time to extubation (p<0.001) and awakening (p=0.04). Conclusions In this meta-analysis, volatile sedation vs propofol caused the increase in ventilator-free days, the reduction in the duration of mechanical ventilation, time to extubation and the troponin release in medical or surgical ICU patients, while in surgical ICU patients the time to awakening was shortened (AU)

Objetivos Evaluar exhaustivamente los estudios revisados por pares que utilizan anestésicos volátiles (AV) o intravenosos (iv) para sedación en unidades de cuidados intensivos (UCI), con la hipótesis de que el tipo de sedación puede tener un impacto en la supervivencia y otros resultados clínicamente relevantes. Diseño Revisión sistemática y metaanálisis de ensayos aleatorizados y no aleatorizados. Ámbito UCI. Pacientes Se incluyeron críticamente enfermos y postoperatorios. Intervenciones Ninguna. Mediciones y resultados principales Los estudios que comparaban los AV vs. los anestésicos iv utilizados en la UCI se buscaron de forma independiente y sistemática. Finalmente, se incluyeron 15 estudios (1.520 pacientes de perfil predominantemente quirúrgico necesitaron sedación de AV durante menos de 96h). El AV no tuvo impacto en la mortalidad por cualquier causa (calidad de los datos probatorios muy baja, Odds Ratio=0,82 [0,60-1,12], p=0,20). Sin embargo, el AV se asoció con una reducción de la duración de la ventilación mecánica (p=0,03) y aumento de los días sin ventilación mecánica (p<0,001). La AV también redujo los niveles postoperatorios de troponina cardíaca (24 horas), el tiempo hasta la extubación (p<0,001) y el despertar (p=0,04). Conclusiones En este metaanálisis, la sedación volátil vs. propofol causó el aumento de los días sin ventilación, la reducción de la duración de la ventilación mecánica, el tiempo hasta la extubación y la liberación de troponina en pacientes de la UCI médica o quirúrgica, mientras que en pacientes de la UCI quirúrgica el tiempo hasta el despertar se acortó (AU)

Halogenated anesthetics vs intravenous hypnotics for short and long term sedation in the intensive care unit: A meta-analysis.

OBJECTIVE: To comprehensively assess peer-reviewed studies using volatile (VA) or intravenous (i/v) anesthetics for sedation in intensive care units (ICUs), with the hypothesis that the type of sedation may have an impact on survival and other clinically relevant outcomes. DESIGN: Systematic review and meta-analysis of randomized and non-randomized trials. SETTING: ICUs. PARTICIPANTS: Critically ill and postoperative patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Studies comparing VA versus i/v anesthetics used in the ICU settings were independently systematically searched. Finally, 15 studies (1520 patients of predominantly surgical profile needed VA sedation for less than 96h) were included. VA had no impact on all-cause mortality (very low quality of evidence, Odds Ratio=0.82 [0.60-1.12], p=0.20). However, VA were associated with a reduction in duration of mechanical ventilation (p=0.03) and increase in ventilator-free days (p<0.001). VA also reduced postoperative levels of cardiac troponin (24h), time to extubation (p<0.001) and awakening (p=0.04). CONCLUSIONS: In this meta-analysis, volatile sedation vs propofol caused the increase in ventilator-free days, the reduction in the duration of mechanical ventilation, time to extubation and the troponin release in medical or surgical ICU patients, while in surgical ICU patients the time to awakening was shortened.

Positive Neuroprotective Effect of Argon Inhalation after Photochemically Induced Ischemic Stroke Model in Rats.

We studied the effect of 2-h inhalation of argon-oxygen mixture (Ar 70%/O2 30%) after photochemically induced stroke and on days 2 and 3 after stroke modeling on the severity of neurological deficit and brain damage (by MRI data) in Wistar rats. Neurological deficit was assessed within 14 days using the limb placement test. MRI and histological study of the brain with an assessment of the size of damage were performed on day 14 after ischemia. Significant differences were obtained in limb placement scores on days 3, 7, and 14, as well as in the volume of ischemic focus by MRI in comparison with the control (ischemia+N2 70%/O2 30%). Inhalation of argon-oxygen mixture for 2 h a day over 3 days after photoinduced stroke decreased the volume of brain damage by 2 times and reduced the severity of neurological deficit.

Transcription Factor Nrf2 as a Potential Therapeutic Target for Prevention of Cytokine Storm in COVID-19 Patients.

Nrf2 is a key transcription factor responsible for antioxidant defense in many tissues and cells, including alveolar epithelium, endothelium, and macrophages. Furthermore, Nrf2 functions as a transcriptional repressor that inhibits expression of the inflammatory cytokines in macrophages. Critically ill patients with COVID-19 infection often present signs of high oxidative stress and systemic inflammation - the leading causes of mortality. This article suggests rationale for the use of Nrf2 inducers to prevent development of an excessive inflammatory response in COVID-19 patients.

COVID-19 and Oxidative Stress.

Pathogenesis of the novel coronavirus infection COVID-19 is the subject of active research around the world. COVID-19 caused by the SARS-CoV-2 is a complex disease in which interaction of the virus with target cells, action of the immune system and the body's systemic response to these events are closely intertwined. Many respiratory viral infections, including COVID-19, cause death of the infected cells, activation of innate immune response, and secretion of inflammatory cytokines. All these processes are associated with the development of oxidative stress, which makes an important contribution to pathogenesis of the viral infections. This review analyzes information on the oxidative stress associated with the infections caused by SARS-CoV-2 and other respiratory viruses. The review also focuses on involvement of the vascular endothelium in the COVID-19 pathogenesis.

[MITOCHONDRIA-TARGETED ANTIOXIDANTS IN THE PREVENTION OF THE CORNEA EROSION WHEN PERFORMING SURGERY UNDER GENERAL ANESTHESIA.]

Despite the use of modern methods of prevention, at least 10% of patients operated on for ophthalmic indications not develop corneal erosion as the indirect complication of general anesthesia. OBJECTIVE: To reduce the number of ophthalmic complications of general anesthesia by prophylactic use of new mito- chondria-targeted antioxidants - Vizomitin (eye drops). MATERIALS AND METHODS: 70 patients, which was supposed to perform the average duration of operations under general anesthesia were randomized into 3 groups depending on the method specific (pharmacological) prevention of corneal erosions: (1) control (specic (pharmacological) prevention was not carried out), (2), using preparation "natural tear, and (3) "Vizomitin" preparation. Postoperative biomicroscopy was performed to assess the condition of the cornea, tear film stability was measured and the height of the tear meniscus. RESULTS: When using eye drops "Vizomitin" value is an indicator of stability of the tear film on the 3rd day after the operation more than in the control group of patients by 51% (p = 0.012) and patients groups, natural tear by 57% (p = 0.013). Surgical interventions performed under general anesthesia, leading to an increase in the number ofpatients with decreased tear meniscus height index of the control group with 4 to 7 patients (p = 0.30) in the group of natural tear from 3 to 11 patients (p = 0.008) . In the group with drug "Vizomitin" the number of such patients is reduced from 7 to 1 (p = 0.018). CONCLUSION: In the surgical procedures under general anesthesia eye drops "Vizomitin" effectively prevents the devel- opment of corneal erosion.

[PERIOPERATIVE MANAGEMENT OF PATIENTS WITH DIABETES MELLITUS.]

The article is devoted to the existence of the problem of intraoperative provide patients with concomitant diabetes mellitus: a disease is not diagnosed in time, it increases the probability of death in the performance of surgery by 50%, where as the timely prevention and preparation reduces the chance of developing specific complications to the level of patients with the general population. The paper discusses the recommendations developed by the British Association ofEndocrinologists 2011 and Russia in 2015, as well as the Association ofAnaesthetists of Great Britain and Ireland (2015), provides practical recommendations for the preoperative preparation, anesthetic and resuscitation provide patients with concomitant diabetes mellitus.

[INDUCTION OF ANESTHESIA ON THE BASIS OF DESFLURANE AND FENTANYL--DANGER IN THE AMBULATORY SURGERY].

PURPOSE: To study the possibility of desflurane use for induction of anesthesia. MATERIALS AND METHODS: We analysed the intra- and immediate postoperative periods in 125 patients. Depending on the intended anesthesia method patients were randomised (the method of the envelopes) and included in one of two study groups: 1--volatile desflurane-based anesthesia (n = 62); 2--volatile sevoflurane-based anesthesia (n = 63). RESULTS: Desflurane based anesthesia led to apnea until the installation of laryngeal mask in 94.5% of patients (of 54), for whom a completion of inhalation induction was possible, whereas sevoflurane based anesthesia.led to apnea occurred only in one patient (1.6%). CONCLUSIONS: "Step up" desflurane-based inhalational induction and sevoflurane-based maximum concentration inhalational induction "without primaryfilling of the circuit" showed no significant in time necessary for achieving an anesthetic concentration essential for LMA installation. In both groups it was 3-5 min. desflurane-based volatile induction with addition of fentanyl led to apnea in 97% of patients and associates with a higher risk of bronchospasm.

[Comparison of pharmacological renal preconditioning with dalargin and lithium ions in the model of gentamycin-induced acute renal failure].

PURPOSE: To examine the efficacy of renal preconditioning effect of dalargin and lithium ions by observing the model of gentamycin-induced acute renalfailure. MATERIALS AND METHODS: The experiments were performed on white rats, male. The influence of dalargin and lithium ions on the development of gentamycin-induced acute renalfailure was studied in vivo. On the first 24 hours after dalargin injections were terminated, the rats were euthanized humanly. After this we took the blood for a biochemistry study and a renal culture for biochemical test and also for the test of gsk-3ß activity. Concentrations of creatinine and urea were studied in serum. The culture samples of renal tubular epithelium before insertion of gentamycin were incubated in dalargin or lithium ions in different concentrations. After that the substratum was immediately changed to gentamycin in different concentrations also and the incubated for 24 hours. After all the standards MTT-test was performed (based on the ability of living cells to reduce the unpainted form by 3-4,5-dimethylthiazol-2-yl-2,5-difenilterarazola to blue crystalline farmazan). RESULTS: Lithium precondition leads to the 250% increase of gsk-3ß concentration (p = 0.035). The same results were observed after injection of dalargin in 50 mcg/kg concentration. Concentration of creatinine was 44% lower in the dalargin group than in the control group (p = 0.022). Concentration of creatinine was 32% lower in the lithium group than in the control group (p = 0.030). Concentration of urea was 27% lower in the lithium group than in the control group (p = 0.049). Morphological inflammatory changes in the control group were more significant also. In vitro studies showed the maximum efficacy in the lithium group. The most effective dalargin concentration was 5 mg/ml. CONCLUSION: Lithium and dalargine preconditioning lowers the signs of gentamycine induced acute renal failure and damage rate of renal parenchyma in vivo and in vitro.

[Molecular mechanisms of ischemic-reperfusion syndrome and its personalized therapy].

Cardiovascular pathologies are the major causes of morbidity and mortality in the world. Cessation of the blood flow in large vessels, supplying tissues with oxygen and substrates, leads to ischemic conditions accompanied by unwanted shifts of oxidative metabolism and rise of the reactive oxygen species (ROS) generation. Small amounts of ROS are essential elements of the cell metabolism, however pathological elevation of ROS jeopardizes the survival of cells, organs and even organisms. Paradoxically, blood flow restoration during prolonged ischemia leads to oxidative stress that is often fatal for a live system. Oxygen paradox appears to be a limiting factor in clinical practice that intuitively seeks for immediate and complete restoration of a damaged blood flow. Mitochondrion is a major ROS source and a key element of pro-apoptotic signaling, however it is clear, that mitochondria are the main target for anti-ischemic treatment. In the present review we consider two ways of such anti-ischemic strategy, bringing ischemic tolerance to the organ through mitochondrial involvement, such as intrinsic, biological, or artificial, pharmacological adaptive systems (preconditioning). The latter is aimed to simulate elements and high efficiency of intrinsic protective system. The role of antioxidants in anti-ischemic therapy and their effects on preconditioning signaling are discussed in the review.

[Selenium metabolism in patients with severe multiple trauma].

GOAL OF THE STUDY: To define a relation between the selenium level and the risk of the development of nosocomial pneumonia in patients with severe multiple trauma depending on the trauma severity and the volume of blood loss. MATERIALS AND METHODS: We measured serum selenium concentration in 40 patients with severe multiple trauma. The ISS score was used to estimate the trauma severity. Patients were divided into 2 groups: group I--25 patients without pneumonia, group II--15 patients with pneumonia. The volume of blood loss was estimated in each group. The oxidative stress was estimated by means of the antioxidant index. RESULTS: For selected groups the significant difference (P < 0.05) in the volume of blood loss was detected. It was shown the significant decrease of selenium concentration (P < 0.05) in both groups in comparison with control for all testing time points (the 6-12 hrs, 24 hrs, 3 and 5-7 days). The mean of selenium concentration in group II was significantly lower in comparison to the group I. A significant difference of selenium concentrations (P < 0.05) between groups were detected on the 6-12 hrs and day 3 from the trauma onset. The antioxidant index was significantly lower in the group II within the 6-12 hrs, 12-24 hrs and 5-7 days (P < 0.05) in comparison to group I. CONCLUSIONS: The severe multiple trauma and severe blood loss lead to a selenium deficiency in the blood serum starting with the first hours from the trauma onset, which leads to the critical level of selenium concentration by the Ist day's end after trauma. It also leads to a pronounced oxidative stress that is reflected in the antioxidant index dynamics. Thus serum selenium concentration may be included in the set of the early prognostic detectors to detect infectious pulmonary complications development at severe multiple trauma, and it could be the basis for the decision to take early prophylaxis using selenium medications.

[Inhalation induction anesthesia: special indications or a routine procedure?].

The efficacy, safety and expediency of various types of the induction anesthesia before the long-lasting major surgery were analyzed. The combination of inhalation of sevoflurane in maximal concentration with phentanil allowed the effective and safe induction and trachea intubation on the 3-4th minute on the background of the nimbex myoplegia. The monoinduction with sevoflurane provides the sufficient analgesia not earlier then after 7-9th minute, which allows the safe intubation at a time. Therefore, the study proved, that the inhalation induction with sevoflurane in various modifications, could be the standard method of inductive anesthesia.

Nephroprotective effect of GSK-3ß inhibition by lithium ions and δ-opioid receptor agonist dalargin on gentamicin-induced nephrotoxicity.

Nephrotoxicity and ototoxicity are the most considerable side effects of aminoglycoside antibiotics, such as gentamicin that seriously limits its application in medicine. The major mechanism of negative effect of gentamicin on kidney cells involves damage of mitochondria and induction of an oxidative stress that causes cell death resulting in kidney dysfunction. In this work we compared effects of the lithium ions and δ-opioid receptors agonist, dalargin on gentamicin-induced kidney injury. It was revealed that LiCl and dalargin treatment reduced renal tubular cell death and diminished kidney injury caused by gentamicin. Both LiCl and dalargin were found to enhance phosphorylation of glycogen synthase kinase 3ß in the kidney which points to induction of nephroprotective signaling pathways. Thus, we conclude that lithium ions and dalargin might be considered as novel promising agents for future use to prevent negative consequences of therapy with aminoglycoside antibiotics.

[Prospects of using non-narcotic analgesics in present-day methods of general anesthesia]. / Perspektivy ispol'zovaniia nenarkoticheskikh analgetikov v sovremennykh metodakh obshchei anestezii.

Efficacies of several relatively new methods of anesthesia are compared. The data of electroencephalographic monitoring, early components of somatosensory evoked potentials, parameters of the central and peripheral hemodynamics (pulsometry supplemented with estimation of photoplethysmography coefficient, among other things), acid-base balance, were used as criteria of the adequacy of analgesia. A total of 369 anesthesiologic modalities are analyzed, which were compared with traditional and modified neuroleptanalgesia (NLA) with inhalation of fluothane vapors. A high efficacy of NLA carried out in parallel with inhalation of gaseous anesthetics (fluothane) was confirmed. If traditional NLA is used in long traumatic operations, fentanyl in dose at least 10 mcg/(kg.h) should be infused during the main stage of the intervention to provide effective anesthesia; during cardiopulmonary bypass surgery fentanyl dose should be at least 15 mcg/(kg.h). Use of moradol as the principal analgesic in surgery on the open heart and aorta and in long traumatic interventions on the thoracic and abdominal organs was found unjustified. Combined total anesthesia with fentanyl, droperidol, seduxen, dalargin, and clofelin may be effectively used for intraoperative protection in interventions of any kind. Clinical significance of the phenomena detected is discussed.

[Intraoperative monitoring of abdominal organs under combined general anesthesia]. / Monitoring vo vremia operatsii na organakh briushnoi polosti v usloviiakh kombinirovannoi obshchei anestezii.

The authors analyse the early components of somatosensory evoked potentials (SSEP) during anesthesia in prolonged and traumatic operations on the abdominal organs (gastrectomy, hemihepatectomy, pancreatoduodenal resection, etc.). A total of 69 patients were examined, among them 32 underwent operations under conditions of classical NLA, 16 with the narcotic analgetics replaced by moradol, and 21 under modified NLA with dalargin. The results of the study and analysis of literature data allow monitoring of the early components of somatosensory evoked potentials to be considered a highly sensitive test for appraising the depth and adequacy of the modern methods of general anesthesia and to be recommended for use, at least in particularly difficult and venturesome operations. It is shown that most significant in the discussed plan is not the absolute value, but changes of the N19-P23 amplitude in the stages of the operation. Increase of the studied SSEP component by 20% and more in relation to the basal level (SSEP amplitude in the patient after adequate preanesthesia) is evidence of insufficient analgesia. Change of N19-P23 latency is less demonstrative. Monitoring of the early components (N19-P23) of SSEP showed that to ensure effective analgesia in prolonged concurrent and combined operations, if the NLA method is chosen, administration of fentanyl in a dose of no less than 12 micrograms/kg/hour is necessary. It is shown that replacement of narcotic analgesics, within the limits of the conducted NLA, by moradol, an agent of the group of agonists-antagonists is poorly effective.(ABSTRACT TRUNCATED AT 250 WORDS)

[Features of general anesthesia and infusion-transfusion therapy in extensive surgery of the organs of the abdominal cavity]. / Osobennosti obshchei anestezii i infuzionno-transfuzionnoi terapii pri rasshirennykh operatsiiakh na organakh briushnoi polosti.

The article discusses variants of infusion-transfusion therapy (ITT) in early stages of expanded operations on the abdominal organs attended by massive blood loss (2 to 4 BCV and more). Seventy-three patients were examined, they underwent resection of the liver (30), pancreatoduodenal resection (37), or removal of a retroperitoneal tumor (6 patients). On the basis of precise study of central and peripheral hemodynamics, acid-base equilibrium, and blood oxygen transport function the authors find it necessary to increase the volumes of ITT to 70-80% BCV in the first stage of the operation with a colloid/crystalloid ratio of 1:4. The described method makes it possible to avoid critical fluctuations of cardiac output and blood pressure in massive bleeding. At the same time, such hemodilution causes no considerable decrease in hemoglobin concentrations (which was 79.0% of the initial level at the beginning of the main stage) and specific oxygen transport (85.0%, respectively). In absolute expression the specific oxygen transport before the hemorrhage is 465 + 29 ml/min/m2, which significantly exceeds the critical value. The authors believe the ITT method to be indicated in inevitable blood loss and absence of serious cardiovascular diseases. From comparative analysis of the different variants of general anesthesia, the authors conclude that the following combination of agents is preferable for the discussed category of patients: phentanyl, droperidol, seduxen, kalipsol (ketamine), and dalargin. Their balanced use ensures stability of the main homeostasis indices in all stages of the intervention; the hepato- and pancreatoprotective properties of dalargin are also of importance.

[Intraoperative computed EEG monitoring for evaluating the adequacy of general anesthesia]. / Intraoperatsionnyi komp'iuternyi EEG-monitoring dlia otsenki adekvatnosti obshchei anestezii.

The article analyses the possibilities of computed EEG monitoring for evaluation of the magnitude and adequacy of the modern methods of general anesthesia: NLA, NLA with halothane inhalation, NLA including Kalipsol bolus administration. An original coefficient, called the adequacy index (AI), was found, which reflects the percentage contribution of deep rhythms (delta and theta) to the total power of the EEG in the range of 0 to 20 Hz. It is shown that the dynamics of this index correlates with the degree of the blocking of entry of sensory nociceptive information into the CNS. The lower boundary of AI-70% was determined, below which the generally accepted signs of anesthesia inadequacy appear: hyperactivity develops, a shift of pH in the acid direction occurs, and the base deficiency increases. It is suggested that determination of AI is used as a highly sensitive and operative test for routine monitoring of the patient's intraoperative condition and express diagnosis of inefficacy of anesthesia.

[Study of xanthine oxidase activity in the brain tissue after administration of dalargin during myoplegia]. / Izuchenie aktivnosti ksantinoksidazy v tkani golovnogo mozga pri vvedenii dalargina na fone mioplegii.

Effect of Dalargin (40 micrograms/kg) on xanthine-oxidase (X) activity in experimental Arduan-induced myoplegia (0.1 mg/kg) was studied in the brain tissue of 70 rats under inhalation anesthesia and artificial ventilation. Neither Dalargin nor Arduan was found separately to induce statistically significant changes in X activity. Dalargin injections in myoplegia caused significant (24.7%) reduction of the enzyme's activity.

[A new method of general anesthesia in pulmonary surgery using dalargin instead of narcotic analgesics]. / Novyi sposob obshchei anestezii pri operatsiiakh na legkikh s primeneniem dalargina vmesto narkoticheskikh anal'getikov.

Intraoperative and early postoperative parameters of the central hemodynamics, oxygen transport function and acid-base status of the blood, and blood lactic and pyruvic acid levels in patients under general anesthesia with dalargin were compared to those under traditional neuroleptic analgesia. The comparative evaluation allowed for a conclusion that general anaesthesia with dalargin provides for a reliable anesthesiological defence and exerts a lower deteriorating effect on the vessels of pulmonary circulation than traditional neuroleptic analgesia.