Search Results (23)

Linezolid, an antimicrobial agent, has been linked to lactic acidosis, oxidative stress, and liver damage. Oxidative stress is considered to play a key role in this damage. Thiamine pyrophosphate (TPP), the active form of thiamine, may prevent lactate accumulation and enhance aerobic capacity. Therefore, this study aimed to evaluate the protective effect of TPP against possible linezolid-induced liver damage and lactic acidosis in rats. Twenty-four male Wistar albino rats were randomly assigned to four groups (n = 6): healthy control (HG), linezolid (LZD), thiamine plus linezolid (TLZD), and TPP plus linezolid (TPLZD). Thiamine and TPP (20 mg/kg, intraperitoneal (i.p.)) were administered once daily, while linezolid (125 mg/kg, per os (p.o.)) was given twice daily (250 mg/kg/day) for 28 days. Animals were euthanized under high-dose anesthesia (with 50 mg/kg, i.p. thiopental sodium). Liver tissues were analyzed for MDA, tGSH, SOD, and CAT, and examined histopathologically. Blood samples were collected prior to euthanasia to assess lactate, LDH, ALT, AST, and TPP levels. In the LZD group, MDA, lactate, ALT, AST, and LDH levels significantly increased, while tGSH, SOD, CAT, and TPP decreased (p < 0.001). Histopathology showed hydropic degeneration, necrosis, and mononuclear cell infiltration (p < 0.05). Thiamine did not prevent these alterations (p > 0.05), whereas TPP significantly prevented both biochemical and histopathological changes (p < 0.05), indicating its protective efficacy. TPP may offer significant protection against linezolid-induced hepatotoxicity and lactic acidosis. Full article

Background: Hypotension is a common adverse effect associated with the use of propofol and sodium thiopental. The objective of this study was to examine the impact of thiopental and propofol on erythrocyte (RBC) nitric oxide (NO) synthase activity and RBC-mediated NO release. Methods: A prospective, interventional in vitro trial. Male patients aged between 18 and 45 years with a classification of American Society of Anesthesiologists (ASA) class I, defined as healthy individuals, were included in this study. Venous blood samples (20 mL) were obtained from patients who met the inclusion criteria. Measurements were performed using the specific fluorescent probes for NO and calcium (Ca²⁺). Propofol and sodium thiopental were added to the suspensions at doses of 100, 250, 500, and 1000 μM and incubated for 30 min. All suspensions were proceeded to flow cytometric analysis. Nitrite/nitrate concentration was measured in the supernatant of RBC suspensions after centrifugation. RBC deformability and aggregation were measured by laser diffraction analysis using an ektacytometer. The primary outcome was to evaluate the effects of sodium thiopental and propofol on RBC-NOS activity. Results: Sodium thiopental caused significant increase in intracellular NO concentrations at all doses studied (p < 0.001). Importantly, the intracellular NO concentration increment was positively correlated with sodium thiopental concentration in the suspensions. The presence of L-N-acetylmethyl-arginine in the experimental medium abolished NO production in RBCs in response to sodium thiopental. Sodium thiopental caused increased nitrite and nitrate levels in the suspension medium in a dose-dependent manner. Incubation with thiopental caused an increase in intracellular free Ca⁺² levels while propofol induced no change. Sodium thiopental and propofol caused significant decrement in RBC aggregation. Conclusions: This study presents the initial evidence of augmented RBC-mediated NO production and release in response to sodium thiopental administration. In contrast to the effects observed with sodium thiopental, our results demonstrated that propofol had no impact on RBC-mediated NO production. Full article

Background: Remifentanil, an ultra-short-acting µ-receptor agonist, is used with propofol for optimal laryngeal mask airway (LMA) insertion. However, no studies have assessed its effects when combined with thiopental on LMA conditions. The combined use of thiopental and remifentanil may offer advantages, such as enhanced cardiovascular and respiratory stability. This study aims to compare the administration of thiopental with different doses of remifentanil to assess their combined effects on LMA insertion conditions and success in a prospective, randomised double-blind study. Method: A total of 100 ASA I–II patients (18–65 years), including both male and female participants, were randomly assigned to four remifentanil dose groups (0.5–3 µg.kg⁻¹). Induction involved thiopental (5 mg.kg⁻¹) after remifentanil. LMA insertion conditions were evaluated using a six-variable scale. Systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), heart rate (HR), and bispectral index monitor (BIS) values, as well as apnoea duration, eyelash reflex loss time, and insertion attempts, were recorded at baseline, before insertion, and at 5 min post-insertion. Results: Time to eyelash reflex loss and LMA insertion were shorter in Groups III and IV than in Groups I and II (p < 0.001). Apnoea duration was longest in Group IV, followed by Group III (p < 0.001). Groups III and IV had significantly better LMA placement, mouth opening, and ease of insertion (p < 0.05). Coughing and gagging were highest in Group I (p < 0.001). SAP, MAP, HR, and DAP were significantly lower in Group IV at various time points (p < 0.05). HR was significantly higher in Group I compared to Groups II and III at multiple time points (p < 0.05). Conclusions: The administration of 5 mg.kg⁻¹ thiopental with 2 μg.kg⁻¹ remifentanil has been found to provide a stable haemodynamic response and 96% excellent or satisfactory laryngeal mask insertion conditions without increasing the duration of apnoea. Full article

Background and Objectives: Dexmedetomidine is a potent selective α₂ receptor agonist with analgesic and sedative effects. Many reports indicate that compared to fentanyl, the combination of dexmedetomidine with propofol provides comparably acceptable conditions for a laryngeal mask airway (LMA). However, no study has evaluated the effectiveness of combined dexmedetomidine and thiopental in LMA insertions compared to that of combined dexmedetomidine and propofol. This prospective, randomized, double-blind study aimed to compare the effects of dexmedetomidine with thiopental or propofol on LMA insertion conditions, hemodynamic responses, and pharyngolaryngeal morbidity, which in this study was defined as the presence of postoperative sore throat, dysphagia, or visible blood in the airway following a laryngeal mask airway (LMA) insertion. Materials and Methods: A total of 80 premedicated ASA I-II patients aged 18–65 years were randomized to the propofol group (Group P, n = 40) or thiopental group (Group T, n = 40). Anesthesia was induced by infusing 1 μg·kg⁻¹ dexmedetomidine over 10 min followed by 2.5 mg·kg⁻¹ propofol or 5 mg·kg⁻¹ thiopental. LMA insertion conditions were evaluated on a scale assessing six variables. Systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), heart rate (HR), and bispectral index values were recorded at baseline; 1 min before; and at 1, 2, 3, 4, and 5 min after an LMA insertion. The baseline values for the systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), heart rate (HR), and bispectral index (BIS) values were recorded before dexmedetomidine infusion. Measurements for all patients were then taken 1 min before and at 1, 2, 3, 4, and 5 min after the LMA insertion Results: Demographic data were similar between the groups. In Group P, the time to loss of eyelash reflex and LMA insertion time were significantly shorter, the apnea duration was significantly longer, and the rates of full jaw opening and optimal LMA insertion conditions were significantly higher when compared with those of Group T (p < 0.05). Group P showed a significantly greater percentage decrease in HR compared to that of Group T at 1 min before and 1, 2, and 3 min after the LMA insertion (p < 0.05). Group T had a greater decrease in SAP and MAP at 1 min before insertion, while the SAP decrease was lower in Group T at 3, 4, and 5 min after insertion. The MAP and DAP values after the LMA insertion showed a greater decrease in Group P compared to in Group T (p < 0.05). The incidence of bradycardia was significantly (p < 0.05) higher in Group P than in Group T. There was no significant difference between the groups in terms of the frequency of hypotension, sore throat, presence of blood, or dysphagia at discharge from the recovery unit (p > 0.05). Conclusions: This study showed that the use of dexmedetomidine with thiopental provided comparably acceptable LMA insertion conditions with more stable hemodynamics compared to propofol. Full article

This Critical Appraisal aims to explore the pharmacokinetics and pharmacodynamics of medications used in organ donors after euthanasia (ODE) and their impact on abdominal organ quality. With the legalization of ODE, the donor pool has expanded, but it has introduced complexities regarding organ quality. This study evaluates existing euthanasia protocols in the Netherlands, Belgium, Spain, and Canada, focusing on differences in the medication types and dosages. Additionally, a literature review assessed the potential hepatotoxic effects of high-dose medications like thiopental, propofol, and non-depolarizing neuromuscular blocking agents. High doses of non-depolarizing neuromuscular blocking agents, particularly rocuronium, are associated with hepatotoxic effects in vitro. Furthermore, thiopental doses exceeding 750 mg significantly increase the risk of liver dysfunction. Recent findings also indicate that high-dose propofol and lidocaine can slightly prolong the time to death, which is crucial for optimizing organ viability in ODE. This study highlights the need to optimize organ donation procedures after euthanasia. Further research is needed to achieve this balance, maintaining the integrity and ethical standards of the euthanasia process while enhancing the outcomes of organ donation. Full article

A hepatocyte cell line was used to determine the hepatotoxicity of sedatives and opioids, as the hepatotoxicity of these drugs has not yet been well characterized. This might pose a threat, especially to critically ill patients, as they often receive high cumulative doses for daily analgosedation and often already have impaired liver function due to an underlying disease or complications during treatment. A well-established biosensor based on HepG2/C3A cells was used for the determination of the hepatotoxicity of commonly used sedatives and opioids in the intensive care setting (midazolam, propofol, s-ketamin, thiopental, fentanyl, remifentanil, and sufentanil). The incubation time was 2 × 3 days with clinically relevant (Cmax) and higher concentrations (C5× and C10×) of each drug in cell culture medium or human plasma. Afterward, we measured the cell count, vitality, lactate dehydrogenase (LDH), mitochondrial dehydrogenase activity, cytochrome P 450 1A2 (CYP1A2), and albumin synthesis. All tested substances reduced the viability of hepatocyte cells, but sufentanil and remifentanil showed more pronounced effects. The cell count was diminished by sufentanil in both the medium and plasma and by remifentanil only in plasma. Sufentanil and remifentanil also led to higher values of LDH in the cell culture supernatant. A reduction of mitochondrial dehydrogenase activity was seen with the use of midazolam and s-ketamine. Microalbumin synthesis was reduced in plasma after its incubation with higher concentrations of sufentanil and remifentanil. Remifentanil and s-ketamine reduced CYP1A2 activity, while propofol and thiopental increased it. Our findings suggest that none of the tested sedatives and opioids have pronounced hepatotoxicity. Sufentanil, remifentanil, and s-ketamine showed moderate hepatotoxic effects in vitro. These drugs should be given with caution to patients vulnerable to hepatotoxic drugs, e.g., patients with pre-existing liver disease or liver impairment as part of their underlying disease (e.g., hypoxic hepatitis or cholestatic liver dysfunction in sepsis). Further studies are indicated for this topic, which may use more complex cell culture models and global pharmacovigilance reports, addressing the limitation of the used cell model: HepG2/C3A cells have a lower metabolic capacity due to their low levels of CYP enzymes compared to primary hepatocytes. However, while the test model is suitable for parental substances, it is not for toxicity testing of metabolites. Full article

In critically ill patients requiring intensive care, increased oxidative stress plays an important role in pathogenesis. Sedatives are widely used for sedation in many of these patients. Some sedatives are known antioxidants. However, no studies have evaluated the direct scavenging activity of various sedative agents on different free radicals. This study aimed to determine whether common sedatives (propofol, thiopental, and dexmedetomidine (DEX)) have direct free radical scavenging activity against various free radicals using in vitro electron spin resonance. Superoxide, hydroxyl radical, singlet oxygen, and nitric oxide (NO) direct scavenging activities were measured. All sedatives scavenged different types of free radicals. DEX, a new sedative, also scavenged hydroxyl radicals. Thiopental scavenged all types of free radicals, including NO, whereas propofol did not scavenge superoxide radicals. In this retrospective analysis, we observed changes in oxidative antioxidant markers following the administration of thiopental in patients with severe head trauma. We identified the direct radical-scavenging activity of various sedatives used in clinical settings. Furthermore, we reported a representative case of traumatic brain injury wherein thiopental administration dramatically affected oxidative-stress-related biomarkers. This study suggests that, in the future, sedatives containing thiopental may be redeveloped as an antioxidant therapy through further clinical research. Full article

Sedatives promote calmness or sleepiness during surgery or severely stressful events. In addition, depression is a mental health issue that negatively affects emotional well-being. A group of drugs called anti-depressants is used to treat major depressive illnesses. The aim of the present work was to evaluate the effects of quercetin (QUR) and linalool (LIN) on thiopental sodium (TS)-induced sleeping mice and to investigate the combined effects of these compounds using a conventional co-treatment strategy and in silico studies. For this, the TS-induced sleeping mice were monitored to compare the occurrence, latency, and duration of the sleep-in response to QUR (10, 25, 50 mg/kg), LIN (10, 25, 50 mg/kg), and diazepam (DZP, 3 mg/kg, i.p.). Moreover, an in silico investigation was undertaken to assess this study’s putative modulatory sedation mechanism. For this, we observed the ability of test and standard medications to interact with various gamma-aminobutyric acid A receptor (GABA_A) subunits. Results revealed that QUR and LIN cause dose-dependent antidepressant-like and sedative-like effects in animals, respectively. In addition, QUR-50 mg/kg and LIN-50 mg/kg and/or DZP-3 mg/kg combined were associated with an increased latency period and reduced sleeping times in animals. Results of the in silico studies demonstrated that QUR has better binding interaction with GABA_A α3, β1, and γ2 subunits when compared with DZP, whereas LIN showed moderate affinity with the GABA_A receptor. Taken together, the sleep duration of LIN and DZP is opposed by QUR in TS-induced sleeping mice, suggesting that QUR may be responsible for providing sedation-antagonizing effects through the GABAergic interaction pathway. Full article

Anxiety is a normal behavioral component. When it is too frequent or appears in inappropriate contexts, it can be considered pathological. Benzodiazepines (BDZs) are drugs with clinical success in anxiety treatment. BDZs act as allosteric modulators of the γ- aminobutyric acid A receptor (GABA_AR). However, these drugs cause adverse effects. Despite the therapeutic advances obtained with BDZs, the search for anxiolytics with fewer adverse effects is ongoing. Studies with monoterpene (–)-borneol [(–)-BOR] demonstrated pharmacological properties such as a partial agonist effect of GABA_AR and an anticonvulsive effect. On the other hand, no work has been developed evaluating the anxiolytic/sedative potential. The objective of this study was to investigate the anxiolytic/sedative effects of (–)-BOR in animal models at doses of 25, 50, and 100 mg/kg (i.p.) and whether there was a molecular interaction with GABA_AR. The anxiolytic effect of monoterpene (–)-BOR was tested on Swiss mice (25–30 g) in three anxiety models: the elevated plus maze test, the open field test, and the light-dark box test. The thiopental-induced sleep time model was a drug screen for the sedative and hypnotic activity related to GABA_ARs. In the molecular docking, the interaction between the GABA_AR molecule and (–)-BOR was performed using the AutoDock 4.2.6 program. The results demonstrated that (–)-BOR has sedative and anxiolytic activity. The molecular docking study revealed that (–)-BOR can interact with GABA_ARs through hydrogen bonds. Full article

Concerns about the safety of anesthetic agents in children arose after animal studies revealed disruptions in neurodevelopment after exposure to commonly used anesthetic drugs. These animal studies revealed that volatile inhalational agents, propofol, ketamine, and thiopental may have detrimental effects on neurodevelopment and cognitive function, but dexmedetomidine and xenon have been shown to have neuroprotective properties. The neurocognitive effects of benzodiazepines have not been extensively studied, so their effects on neurodevelopment are undetermined. However, experimental animal models may not truly represent the pathophysiological processes in children. Multiple landmark studies, including the MASK, PANDA, and GAS studies have provided reassurance that brief exposure to anesthesia is not associated with adverse neurocognitive outcomes in infants and children, regardless of the type of anesthetic agent used. Full article

Pain management is necessary for all surgical procedures. Little scientific evidence about drug efficacy in donkeys is available. The aim of this study was to evaluate the analgesic effect of butorphanol in donkeys undergoing orchiectomy under total intravenous anaesthesia with guaifenesin-ketamine-detomidine. A randomized blinded prospective clinical trial (Protocol n. 2021/0000338), was carried out on 18 clinically healthy donkeys undergoing bilateral orchiectomy. Patients were assigned to Group D (n = 8) or Group DB (n = 10) if receiving intravenous detomidine or detomidine-butorphanol respectively, before induction of general anaesthesia with ketamine-diazepam. Intraoperative muscle relaxation, nystagmus, palpebral reflex, heart and respiratory rate, and non-invasive blood pressure were evaluated every 2 min; time to prepare the patient, duration of surgery and anaesthesia and recovery score were recorded. Group D had significantly longer surgical time, higher heart rate, higher systolic and mean blood pressure (p < 0.05; repeated measure ANOVA), increased muscle rigidity and expression of palpebral reflex (p < 0.05; Mann–Whitney U test) than group DB. Top-ups with thiopental were statistically higher in Group D. Butorphanol and detomidine together produced a more stable anaesthetic plan. The low dosage of opioid and alpha-2-agonists and reduced rescue anaesthesia are responsible for a safer and more superficial anaesthesia, which is mandatory under field conditions. Full article

Although thiopental improved neurological outcomes in several animal studies, there are still insufficient clinical data examining the efficacy of thiopental for patients undergoing surgical clipping of unruptured intracranial aneurysm (UIA). This study validated the effect of thiopental and investigated risk factors associated with postoperative neurological complications in patients undergoing surgical clipping of UIA. In total, 491 patients who underwent aneurysm clipping were included in this retrospective cohort study. Data regarding demographics, aneurysm characteristics, and use of thiopental were collected from electronic medical records. Propensity score matching and logistic regression analysis were used. After propensity score matching, the thiopental group showed a lower incidence of the postoperative neurological complications than non-thiopental group (5.5% vs. 17.1%, p = 0.001). In multivariate analysis, thiopental reduced the risk of postoperative neurological complications (odds ratio (OR) 0.26, 95% confidence interval (CI) 0.13 to 0.51, p < 0.001) while aneurysm size ≥ 10 mm (OR 4.48, 95% CI 1.69 to 11.87, p = 0.003), and hyperlipidemia (OR 2.24, 95% CI 1.16 to 4.32, p = 0.02) increased the risk of postoperative neurological complications. This study showed that thiopental was associated with the lower risk of neurological complications after clipping of UIA. Full article

Patients with sepsis-associated encephalopathy (SAE) can develop convulsive or nonconvulsive seizures. The cytokine storm and the overwhelming systemic inflammation trigger the electric circuits that promote seizures. Several neurologic symptoms, associated with this disease, range from mild consciousness impairment to coma. Focal or generalized convulsive seizures are frequent in sepsis, although nonconvulsive seizures (NCS) are often misdiagnosed and prevalent in SAE. In order to map the trigger zone in all patients that present focal or generalized seizures and also to detect NCS, EEG is indicated but continuous EEG (cEEG) is not very widespread; timing, duration, and efficacy of this tool are still unknown. The long-term risk of seizures in survivors is increased. The typical stepwise approach of seizures management begins with benzodiazepines and follows with anticonvulsants up to anesthetic drugs such as propofol or thiopental, which are able to induce burst suppression and interrupt the pathological electrical circuits. This narrative review discusses pathophysiology, clinical presentation, diagnosis and treatment of seizures in sepsis. Full article

Syzygium fruticosum (SF), a valuable Bangladeshi fruit, is considered an alternative therapeutic agent. Mainly, seeds are used as nutritional phytotherapy to ease physical and mental status by preventing chronic diseases. Here, we scrutinized the S. fruticosum seed’s fundamental importance in traditional medicine by following an integrated approach combining in vivo, in vitro, and in silico studies. The SF was fractionated with different solvents, and the ethyl acetate fraction of SF (EaF-SF) was further studied. Mice treated with EaF-SF (200 and 400 mg/kg) manifested anxiolysis evidenced by higher exploration in elevated plus maze and hole board tests. Similarly, a dose-dependent drop of immobility time in a forced swimming test ensured significant anti-depressant activity. Moreover, higher dose treatment exposed reduced exploratory behaviour resembling decreased movement and prolonged sleeping latency with a quick onset of sleep during the open field and thiopental-induced sleeping tests, respectively. In parallel, EaF-SF significantly (p < 0.001) and dose-dependently suppressed acetic acid and formalin-induced pain in mice. Also, a noteworthy anti-inflammatory activity and a substantial (p < 0.01) clot lysis activity (thrombolytic) was observed. Gas chromatography-mass spectrometry (GC–MS) analysis resulted in 49 bioactive compounds. Among them, 12 bioactive compounds with Lipinski’s rule and safety confirmation showed strong binding affinity (molecular docking) against the receptors of each model used. To conclude, the S. fruticosum seed is a prospective source of health-promoting effects that can be an excellent candidate for preventing degenerative diseases. Full article

The subject of the work was the synthesis of new derivatives of1H-pyrrolo[3,4-c]pyridine-1,3(2H)-dione with potential analgesic and sedative activity. Eight compounds werereceived. The analgesic activity of the new compounds was confirmed in the “hot plate” test and in the “writhing” test. All tested imides 8–15 were more active in the “writhing” test than aspirin, and two of them, 9 and 11, were similar to morphine. In addition, all of the new imides inhibited the locomotor activity in mice to a statistically significant extent, and two of them also prolonged the duration of thiopental sleep.On the basis of the results obtained for the previously synthesized imides and the results presented in this paper, an attempt was madeto determine the relationship between thechemical structure of imides and their analgesic and sedativeproperties. Full article