Východiska: Pooperační ileus (pooperační dysfunkce) je závažná komplikace vyskytující se především u pacientů s rizikovými faktory a u pacientů po akutních, dlouhotrvajících operačních výkonech. Jeho etiologie je multifaktoriální, podílí se na ní jak zánětlivé, tak i neurogenní, hormonální a farmakologické faktory. V prevenci a léčbě se snažíme uplatnit především nefarmakologické postupy, ovlivnit reverzibilní etiologické faktory a v pooperačním období nejlépe implementovat a využít ERAS postupy. Další možností je snaha o ovlivnění tohoto stavu farmaky. V diferenciální diagnostice je třeba odlišit krátkodobé zhoršení střevní motility, která je běžná prakticky po každém nitrobřišním výkonu. Cíl: Cílem práce je popsat možnosti farmakologické intervence u takto postižených pacientů. Na základě současné úrovně poznání práce analyzuje účinnost současně používaných farmak především ze skupiny takzvaných prokinetik. Závěr: Pooperační ileus stále představuje závažnou komplikaci. Možnosti farmakologické intervence jsou omezené, účinný se jeví být neostigmin a v prevenci v České republice nedostupný alvimopan. Nadějnými preparáty se také jeví 5-hydroxytryptamin 4 (5HT4) agonisté, zde je ale třeba dalších studií. Použití inhibitorů COX-2 je stále diskutabilní.

Introduction: Postoperative ileus is a severe condition occurring especially in high-risk patients following acute and prolonged surgical procedures. Multiple factors are described as important in etiology, such as inflammation as well as neurological, hormonal and pharmacological influences. In prevention and treatment, we try to apply non-pharmaceutical procedures, to influence reversible etiological factors and, in postoperative period, to implement and use ERAS procedures. Drugs are the other possibility how to influence this pathology. Short-term impairment of intestinal motility following the most of the intraabdominal surgeries must be also taken in count in the differential diagnosis and treatment. Study aim: We try to describe all possibilities of pharmacological treatment and prevention of the postoperative ileus. Effectiveness of drugs used in present praxis, especially group of so-called prokinetics is analyzed. Conclusion: Postoperative ileus is still recognized as severe complication. Pharmacological treatment options are limited, only a few substances have evident positive impact (neostigmin for treatment and alvimopan – not registered in the Czech Republic for prevention). More evidence is necessary for positive effect of 5-hydroxytryptamine 4 (5HT4) agonists, and the effect of selective COX-2 inhibitors is still controversial.

• MeSH
• Ileus * diagnosis   etiology   drug therapy   MeSH
• Humans MeSH
• Neostigmine administration & dosage   therapeutic use   MeSH
• Postoperative Complications * drug therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Článek podává přehled využití kurare od prostředku k lovu až po použití v medicíně jako svalového relaxancia a přehled dalších látek, které ho následovaly. Jsou uvedeny i osoby, které se do této historie významně zapsaly. Dále je popsán i vývoj antidot svalových relaxancií, objev nikotinového acetylcholinového receptoru a využití a zneužití svalových relaxancií mimo operační sály.

The article gives an overview of the use of curare from a poison of hunting arrows to its use in medicine as a muscle relaxant and a review of other substances that followed. People who have made a significant contribution to this history are listed. The development of muscle relaxant antidotes, the discovery of the nicotinic acetylcholine receptor, and the use and abuse of muscle relaxants outside of operating rooms are described.

• MeSH
• History, 19th Century MeSH
• History, 20th Century MeSH
• Curare history   MeSH
• Humans MeSH
• Neostigmine history   MeSH
• Neuromuscular Agents * history   MeSH
• Receptors, Cholinergic history   MeSH
• Succinylcholine history   MeSH
• Check Tag
• History, 19th Century MeSH
• History, 20th Century MeSH
• Humans MeSH
• Publication type
• Historical Article MeSH

Nicotinic receptors (NRs) play an important role in the cholinergic regulation of heart functions, and converging evidence suggests a diverse repertoire of NR subunits in the heart. A recent hypothesis about the plasticity of β NR subunits suggests that β2-subunits and β4-subunits may substitute for each other. In our study, we assessed the hypothetical β-subunit interchangeability in the heart at the level of mRNA. Using two mutant mice strains lacking β2 or β4 NR subunits, we examined the relative expression of NR subunits and other key cholinergic molecules. We investigated the physiology of isolated hearts perfused by Langendorff's method at basal conditions and after cholinergic and/or adrenergic stimulation. Lack of β2 NR subunit was accompanied with decreased relative expression of β4-subunits and α3-subunits. No other cholinergic changes were observed at the level of mRNA, except for increased M3 and decreased M4 muscarinic receptors. Isolated hearts lacking β2 NR subunit showed different dynamics in heart rate response to indirect cholinergic stimulation. In hearts lacking β4 NR subunit, increased levels of β2-subunits were observed together with decreased mRNA for acetylcholine-synthetizing enzyme and M1 and M4 muscarinic receptors. Changes in the expression levels in β4-/- hearts were associated with increased basal heart rate and impaired response to a high dose of acetylcholine upon adrenergic stimulation. In support of the proposed plasticity of cardiac NRs, our results confirmed subunit-dependent compensatory changes to missing cardiac NRs subunits with consequences on isolated heart physiology.NEW & NOTEWORTHY In the present study, we observed an increase in mRNA levels of the β2 NR subunit in β4-/- hearts but not vice versa, thus supporting the hypothesis of β NR subunit plasticity that depends on the specific type of missing β-subunit. This was accompanied with specific cholinergic adaptations. Nevertheless, isolated hearts of β4-/- mice showed increased basal heart rate and a higher sensitivity to a high dose of acetylcholine upon adrenergic stimulation.

• MeSH
• Acetylcholine pharmacology   MeSH
• Muscarinic Antagonists pharmacology   MeSH
• Atropine pharmacology   MeSH
• Cholinesterase Inhibitors pharmacology   MeSH
• Hexamethonium pharmacology   MeSH
• Isoproterenol pharmacology   MeSH
• Myocardium metabolism   MeSH
• Mice, Knockout MeSH
• Mice MeSH
• Neostigmine pharmacology   MeSH
• Receptors, Nicotinic metabolism   MeSH
• Heart drug effects   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Cíl studie: Cílem studie bylo testování hypotézy, že použití sugammadexu zkracuje dobu do extubace ve srovnání s použitím neostigminu u pacientů podstupujících roboticky asistované urologické výkony. Typ studie: Monocentrická prospektivní randomizovaná studie. Typ pracoviště: Krajská a univerzitní nemocnice. Materiál a metoda: Šedesát dospělých pacientů podstupujících laparoskopický roboticky asistovaný urologický výkon bez kontraindikací k podání rokuronia, neostigminu a sugammadexu, kterým byla peroperačně monitorována hloubka nervosvalové blokády. Pacienti byli randomizováni do skupiny s antagonizací nervosvalové blokády neostigminem nebo sugammadexem. Primárním cílem byla doba od podání antidota do extubace. Výsledky: Do studie bylo zařazeno 61 pacientů ASA I–III. Doba do extubace byla významně kratší ve skupině s podáním sugammadexu v porovnání s neostigminem: 10; 3,5–35 minut, resp. 45; 16–88 minut, p < 0,00001 (data ve formátu průměr; rozmezí minimum–maximum). Pacienti ve skupině se sugammadexem byli též významně dříve transportováni z operačního sálu. V kvalitě i rychlosti zotavení po 72 hodinách nebyly mezi skupinami odlišnosti. Závěr: Sugammadex statisticky významně urychlil čas od podání do extubace u pacientů ASA I–III po roboticky asistovaném urologickém laparoskopickém výkonu v porovnání s neostigminem. Sugammadex vedl ke zkrácení času transportu pacientů z operačního sálu.

Objective: The aim of the study was to test the hypothesis that the use of sugammadex shortens the time to extubation compared to the use of neostigmine in patients undergoing robotically assisted urological procedures. Design: Monocentric prospective randomized study. Setting: Tertiary Care Hospital. Material and methods: Sixty adult patients undergoing robotic-assisted urological laparoscopic surgery without contraindications to the administration of rocuronium, neostigmine and sugammadex, with perioperative monitoring of the depth of neuromuscular blockade. Patients were randomized to the group with antagonization of the neuromuscular blockade with either neostigmine or sugammadex. Primary outcome was time to extubation from injection of the antagonist. Results: Sixty-one patients with ASA I–III were enrolled. The time to extubation was significantly shorter in the sugammadex group compared to neostigmine group: 10; 3.5–35 minutes, 45; 16–88 minutes respectively, p < 0.00001 (data shown as an average; minimum – maximum range). In addition, patients in the sugammadex group were transported significantly faster from the operating room. There were no differences in the quality and rate of recovery in 72 hours postoperatively. Conclusion: Sugammadex statistically significantly accelerated the time from administration to extubation in ASA I–III patients after robotic-assisted urologic laparoscopic surgery compared to neostigmine. Thus, sugammadex significantly accelerated the patients’ operating room turn-over time.

• MeSH
• Airway Extubation MeSH
• Humans MeSH
• Neostigmine therapeutic use   MeSH
• Neuromuscular Blockade MeSH
• Randomized Controlled Trials as Topic MeSH
• Robotic Surgical Procedures * MeSH
• Sugammadex * therapeutic use   MeSH
• Urologic Surgical Procedures MeSH
• Check Tag
• Humans MeSH

Periferní myorelaxancia jsou nedílnou součástí moderní anesteziologie. Zajišťují především usnadnění chirurgického výkonu a dobré podmínky k intubaci. Oproti minulosti, kdy byla pozornost stran nervosvalové blokády zaměřena právě na tyto aspekty, dominuje nyní zájem o monitoraci hloubky nervosvalové blokády v průběhu výkonu a její zvrat. Aktivní zvrat nervosvalové blokády za přítomné objektivní monitorace míry zotavení je důležitým bezpečnostním prvkem použití myorelaxancií. Článek přináší pohled především na aktuální trendy použití periferních svalových relaxancií.

Peripheral muscle relaxants are an integral part of modern anaesthesiology. They ensure, in particular, facilitation of the surgical procedure and good conditions for intubation. Unlike in the past, when attention in terms of neuromuscular blockade was paid to these very aspects, there now predominates an interest in monitoring the depth of neuromuscular blockade during the course of the procedure and its reversal. Active reversal of neuromuscular blockade in the presence of objective monitoring of the recovery rate is an important safety factor of muscle relaxant use. The article deals with the current trends in the use of peripheral muscle relaxants.

• MeSH
• Humans MeSH
• Neostigmine pharmacology   adverse effects   MeSH
• Neuromuscular Blockade methods   adverse effects   MeSH
• Neuromuscular Agents * history   pharmacokinetics   adverse effects   MeSH
• Perioperative Period MeSH
• Rocuronium administration & dosage   pharmacology   MeSH
• Sugammadex administration & dosage   pharmacology   adverse effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

Project "Modern myorelaxation procedure and reversal of neuromuscular blockade during general anesthesia for caesarean section" aims to introduce in other indications for rapid induction of general anesthesia common and safe, alternative method of combining short-acting intravenous anesthetics propofol and fast-onset non-depolarizing muscle relaxant rocuronium into the clinical practice and demonstrate the efficacy and safety in this indication. At the same time to demonstrate the benefits of using modern reversal of neuromuscular blockade by sugammadex in termination the caesarean section under general anesthesia. Both procedures will be monitored by clinical observation, monitoring instrumentation and laboratory examination of mother and fetus (newborn) in various stages of peripartal period. The main benefit of this procedure will be in particular risk groups of mothers which are indicated by Caesarean Section while neuraxial blockade is contraidicated.

Projekt "Moderní postup myorelaxace a zvratu nervosvalové blokády při celkové anestezie u císařského řezu" si klade za cíl zavést do klinické praxe, v jiných indikacích rychlého úvodu do celkové anestezie běžný a bezpečný, alternativní postup kombinací ultrakrátce působícího intravenózního anestetika propofol a rychle nastupujícího nedepolarizujícího myorelaxans rokuronium a prokázat jeho účinnost a bezpečnost i v této indikaci. Zároveň prokáže výhody užití moderního zvratu nervosvalové blokády sugammadexem po proběhlém císařském řezu v celkové anestezii. Oba postupy budou monitorovány klinickým pozorováním, přístrojovým sledováním a laboratorním zkoumáním matky i plodu (novorozence) v různých fázích peripartálního období. Ze zavedení postupu budou těžit zejména rizikové skupiny pacientek, u nichž je indikován císařský řez a zároveň kontraindikována neuraxiální blokáda.

• MeSH
• Androstanols MeSH
• Anesthesia, General MeSH
• Cesarean Section MeSH
• Neuromuscular Depolarizing Agents MeSH
• gamma-Cyclodextrins MeSH
• Drug Therapy, Combination MeSH
• Neuromuscular Nondepolarizing Agents MeSH
• Neostigmine MeSH
• Neuromuscular Blockade MeSH
• Monitoring, Intraoperative MeSH
• Anesthesia, Obstetrical MeSH
• Propofol MeSH
• Succinylcholine analogs & derivatives   MeSH
• Pregnant People MeSH
• Pregnancy Trimester, Third MeSH
• Airway Management MeSH
• Risk Adjustment MeSH

• Conspectus
• Gynekologie. Porodnictví
• NML Fields
• gynekologie a porodnictví
• anesteziologie a intenzivní lékařství
• NML Publication type
• závěrečné zprávy o řešení grantu IGA MZ ČR

BACKGROUND: Rocuronium for cesarean delivery under general anesthesia is an alternative to succinylcholine for rapid-sequence induction of anesthesia because of the availability of sugammadex for reversal of neuromuscular blockade. However, there are no large well-controlled studies in women undergoing general anesthesia for cesarean delivery. The aim of this noninferiority trial was to determine whether rocuronium and sugammadex confer benefit in time to tracheal intubation (primary outcome) and other neuromuscular blockade outcomes compared with succinylcholine, rocuronium, and neostigmine in women undergoing general anesthesia for cesarean delivery. METHODS: We aimed to enroll all women undergoing general anesthesia for cesarean delivery in the 2 participating university hospitals (Brno, Olomouc, Czech Republic) in this single-blinded, randomized, controlled study. Women were randomly assigned to the ROC group (muscle relaxation induced with rocuronium 1 mg/kg and reversed with sugammadex 2-4 mg/kg) or the SUX group (succinylcholine 1 mg/kg for induction, rocuronium 0.3 mg/kg for maintenance, and neostigmine 0.03 mg/kg for reversal of the neuromuscular blockade). The interval from the end of propofol administration to tracheal intubation was the primary end point with a noninferiority margin of 20 seconds. We recorded intubating conditions (modified Viby-Mogensen score), neonatal outcome (Apgar score <7; umbilical artery pH), anesthesia complications, and subjective patient complaints 24 hours after surgery. RESULTS: We enrolled 240 parturients. The mean time to tracheal intubation was 2.9 seconds longer in the ROC group (95% confidence interval, -5.3 to 11.2 seconds), noninferior compared with the SUX group. Absence of laryngoscopy resistance was greater in the ROC than in the SUX groups (ROC, 87.5%; SUX, 74.2%; P = 0.019), but there were no differences in vocal cord position (P = 0.45) or intubation response (P = 0.31) between groups. No statistically significant differences in incidence of anesthesia complications or in neonatal outcome were found (10-minute Apgar score <7, P = 0.07; umbilical artery pH, P = 0.43). The incidence of postpartum myalgia was greater in the SUX group (ROC 0%; SUX 6.7%; P = 0.007). The incidence of subjective complaints was lower in the ROC group (ROC, 21.4%; SUX, 37.5%; P = 0.007). CONCLUSIONS: We conclude that rocuronium for rapid-sequence induction is noninferior for time to tracheal intubation and is accompanied by more frequent absence of laryngoscopy resistance and lower incidence of myalgia in comparison with succinylcholine for cesarean delivery under general anesthesia.

• MeSH
• Androstanols administration & dosage   adverse effects   MeSH
• Antidotes administration & dosage   adverse effects   MeSH
• Time Factors MeSH
• Anesthesia, General * adverse effects   MeSH
• Cholinesterase Inhibitors administration & dosage   adverse effects   MeSH
• Cesarean Section * adverse effects   MeSH
• Adult MeSH
• gamma-Cyclodextrins administration & dosage   adverse effects   MeSH
• Intubation, Intratracheal MeSH
• Single-Blind Method MeSH
• Laryngoscopy MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Myalgia etiology   prevention & control   MeSH
• Neuromuscular Nondepolarizing Agents administration & dosage   adverse effects   MeSH
• Neostigmine administration & dosage   adverse effects   MeSH
• Neuromuscular Blockade adverse effects   methods   MeSH
• Pain, Postoperative etiology   prevention & control   MeSH
• Anesthesia, Obstetrical adverse effects   methods   MeSH
• Succinylcholine administration & dosage   MeSH
• Pregnancy MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Comparative Study MeSH
• Geographicals
• Czech Republic MeSH

Electrogastrography (EGG) is a non-invasive method for the assessment of gastric myoelectrical activity. Porcine EGG is comparable with human one. The purpose of this study was to evaluate the effect of atropine and neostigmine on the EGG in experimental pigs. Adult female pigs were administrated atropine (1.5 mg i.m., n=6) and neostigmine (0.5 mg i.m., n=6) after the baseline EGG, followed by a 90-min trial recording (MMS, Enschede, the Netherlands). Running spectral analysis was used for the evaluation. The results were expressed as dominant frequency of slow waves and EGG power (areas of amplitudes). Neostigmine increased continuously the dominant frequency and decreased significantly the EGG power. Atropine did not change the dominant frequency significantly. However, atropine increased significantly the EGG power (areas of amplitudes) from basal values to the maximum at the 10-20-min interval. After that period, the areas of amplitudes decreased significantly to the lowest values at the 60-90-min interval. In conclusion, cholinergic and anticholinergic agents affect differently EGG in experimental pigs.

• MeSH
• Muscarinic Antagonists pharmacology   MeSH
• Atropine pharmacology   MeSH
• Time Factors MeSH
• Cholinesterase Inhibitors pharmacology   MeSH
• Electrodiagnosis MeSH
• Myoelectric Complex, Migrating drug effects   MeSH
• Models, Animal MeSH
• Neostigmine pharmacology   MeSH
• Swine MeSH
• Stomach drug effects   MeSH
• Animals MeSH
• Check Tag
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Cholinesterases are enzymes able to hydrolyze the neurotransmitter acetylcholine and thus to terminate transmission. Once the enzymes are inhibited, excitotoxicity can appear in the adjacent cells. It is well known that oxidative stress is involved in the toxicity of cholinesterase inhibitors. Commonly, stress follows inhibition of cholinesterases and disappears shortly afterwards. In the present experiment, it was decided to test the impact of an inhibitor, neostigmine, on oxidative stress in BALB/c mice after a longer interval. The animals were sacrificed three days after onset of the experiment and spleens and livers were collected. Reduced glutathione (GSH), glutathione reductase (GR), glutathione S-transferase (GST), thiobarbituric acid reactive substances (TBARS), ferric reducing antioxidant power (FRAP), caspase-3 and activity of acetylcholinesterase (AChE) were assayed. The tested markers were not altered with exceptions of FRAP. The FRAP values indicate accumulation of low molecular weight antioxidants in the examined organs. The role of low molecular weight antioxidants in the toxicity of AChE inhibitors is discussed.

• Keywords
• excitotoxicita,
• MeSH
• Acetylcholinesterase MeSH
• Antioxidants MeSH
• Butyrylcholinesterase MeSH
• Cholinesterase Inhibitors * toxicity   MeSH
• Enzyme Assays MeSH
• Glutathione MeSH
• Homeostasis * drug effects   MeSH
• Liver enzymology   drug effects   MeSH
• Mice, Inbred BALB C MeSH
• Neostigmine toxicity   MeSH
• Oxidative Stress * drug effects   MeSH
• Spleen enzymology   drug effects   MeSH
• Research MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH

• Keywords
• antagonizace nervosvalové blokády,
• MeSH
• Adjuvants, Anesthesia therapeutic use   MeSH
• Anesthesia * methods   MeSH
• Muscarinic Antagonists therapeutic use   MeSH
• Atropine * adverse effects   therapeutic use   MeSH
• Time Factors MeSH
• Cholinesterase Inhibitors therapeutic use   MeSH
• Drug Therapy, Combination adverse effects   MeSH
• Humans MeSH
• Neuromuscular Nondepolarizing Agents administration & dosage   therapeutic use   MeSH
• Neostigmine * administration & dosage   pharmacology   therapeutic use   MeSH
• Neuromuscular Blockade MeSH
• Receptors, Muscarinic drug effects   MeSH
• Check Tag
• Humans MeSH