Most studies examining tramadol metabolism have been carried out in non-surgical patients and with oral tramadol. The aim of this study was 1) to measure concentrations of tramadol,
-demethyltramadol ...(ODT), and
-demethyltramadol (NDT) in the surgical patients admitted to the intensive care unit (ICU) within the first 24 postoperative hours after intravenous application of tramadol, and 2) to examine the effect of systemic inflammation on tramadol metabolism and postoperative pain.
A prospective observational study was carried out in the surgical ICU in the tertiary hospital. In the group of 47 subsequent patients undergoing major abdominal surgery, pre-operative blood samples were taken for
polymorphism analysis. Systemic inflammation was assessed based on laboratory and clinical indicators. All patients received 100 mg of tramadol intravenously every 6 h during the first postoperative day. Postoperative pain was assessed before and 30 min after tramadol injections. Tramadol, ODT, and NDT concentrations were determined by high-performance liquid chromatography.
analysis revealed 2 poor (PM), 22 intermediate (IM), 22 extensive (EM), and 1 ultrafast metabolizer. After a dose of 100 mg of tramadol, t
of 4.8 (3.2-7.6) h was observed. There were no differences in tramadol concentration among metabolic phenotypes. The area under the concentration-time curve at the first dose interval (AUC
) of tramadol was 1,200 (917.9-1944.4) μg ×h ×L
. NDT concentrations in UM were below the limit of quantification until the second dose of tramadol was administrated, while PM had higher NDT concentrations compared to EM and IM. ODT concentrations were higher in EM, compared to IM and PM. ODT AUC
was 229.6 (137.7-326.2) μg ×h ×L
and 95.5 (49.1-204.3) μg ×h ×L
in EM and IM, respectively (
= 0.004). Preoperative cholinesterase activity (ChE) of ≤4244 U L
was a cut-off value for a prediction of systemic inflammation in an early postoperative period. NDT AUC
were significantly higher in patients with low ChE compared with normal ChE patients (
= 0.006). Pain measurements have confirmed that sufficient pain control was achieved in all patients after the second tramadol dose, except in the PM.
polymorphism is a major factor in
-demethylation, while systemic inflammation accompanied by low ChE has an important role in the
-demethylation of tramadol in postoperative patients. Concentrations of tramadol, ODT, and NDT are lower in surgical patients than previously reported in non-surgical patients. Clinical Trial Registration: ClinicalTrials.gov, NCT04004481.
Coagulation disorders in critically ill patients presenting with bleeding can be multicausal. The drugs applied can interfere and impair the coagulation cascade. Point-of-care (POC) coagulation ...assays may resolve difficult therapeutic situations in critical illness. We report on a 73-year-old critically ill male patient with massive hematuria after bladder lithotripsy. The patient was on low molecular weight heparin therapy due to recent pulmonary embolism. He was subjected to repeated surgical hemostasis which was ineffective despite massive transfusion protocol and normal standard coagulation profile. Additional POC coagulation assays were obtained and were indicative of platelet dysfunction. We revised his medical therapy and suspected the possible drug influence on platelet aggregation. After discontinuation of target drug, platelet aggregation increased whereas hematuria stopped. Coagulation disorders in intensive care unit patients are often multifactorial. Standard laboratory tests are unreliable in complex refractory bleeding and may result in inappropriate therapeutic decisions. Stepwise approach with assessment of clinical parameters, present therapy, and a combination of POC coagulation tests is the key to optimal therapeutic management.Coagulation disorders in critically ill patients presenting with bleeding can be multicausal. The drugs applied can interfere and impair the coagulation cascade. Point-of-care (POC) coagulation assays may resolve difficult therapeutic situations in critical illness. We report on a 73-year-old critically ill male patient with massive hematuria after bladder lithotripsy. The patient was on low molecular weight heparin therapy due to recent pulmonary embolism. He was subjected to repeated surgical hemostasis which was ineffective despite massive transfusion protocol and normal standard coagulation profile. Additional POC coagulation assays were obtained and were indicative of platelet dysfunction. We revised his medical therapy and suspected the possible drug influence on platelet aggregation. After discontinuation of target drug, platelet aggregation increased whereas hematuria stopped. Coagulation disorders in intensive care unit patients are often multifactorial. Standard laboratory tests are unreliable in complex refractory bleeding and may result in inappropriate therapeutic decisions. Stepwise approach with assessment of clinical parameters, present therapy, and a combination of POC coagulation tests is the key to optimal therapeutic management.
Tramadol is a commonly used analgesic in intensive care units (ICUs) for acute postoperative pain. Conversion of tramadol into active metabolites may be impaired in inflammatory states. ...Catechol-O-methyltransferase may influence pain. The aim of the study was to examine differences in the analgesic effect of tramadol between ICU patients with and without signs of systemic inflammation. Forty-three patients were admitted to ICU after a major abdominal surgery. The patients received a dose of 100 mg of tramadol intravenously every 6 hours during the first 24 hours after surgical procedure. Pain scores were measured by the Numeric Rating Scale before and 30 minutes after tramadol administration in awake patients. Systemic inflammation was considered when at least two of the following postoperative parameters were present in the first 24 hours of ICU admission: fever or hypothermia, tachycardia, pCO.sub.2 <4.3 kPa, white blood cells >12000/mm (3) or <4000/mm.sup.3, or preoperative value of C-reactive protein (CRP) >50 mg/L or/and procalcitonin (PCT) >0.5 mg/L. Catechol-O-methyltransferase was analyzed postoperatively. Fifteen (34.8%) patients met the criteria for systemic inflammation. Tramadol was proven to be an effective analgesic for the treatment of postoperative pain regardless of the presence of systemic inflammation (p<0.05). Lower perception of pain before tramadol application was observed in patients with systemic inflammation, but the difference was not significant. A negative correlation was observed between the preoperative values of CRP and PCT and the analgesic effect of tramadol assessed at the second measurement point (r=-0.3S8, p=0.03, and r=-0.364, p=0.02, respectively). Catechol-O-methyltransferase variants were not in correlation with pain and opioid consumption. Based on our findings, tramadol is effective in lowering pain scores after major abdominal surgery irrespective of the presence of systemic inflammation. Key words: Analgesia; Critical care; Systemic inflammatory response; Catechol-O-methyltransferase; Tramadol
The aim of this post hoc analysis of a large cohort study was to evaluate the association between night-time surgery and the occurrence of intraoperative adverse events (AEs) and postoperative ...pulmonary complications (PPCs).
LAS VEGAS (Local Assessment of Ventilatory Management During General Anesthesia for Surgery) was a prospective international 1-week study that enrolled adult patients undergoing surgical procedures with general anaesthesia and mechanical ventilation in 146 hospitals across 29 countries. Surgeries were defined as occurring during ‘daytime’ when induction of anaesthesia was between 8:00 AM and 7:59 PM, and as ‘night-time’ when induction was between 8:00 PM and 7:59 AM.
Of 9861 included patients, 555 (5.6%) underwent surgery during night-time. The proportion of patients who developed intraoperative AEs was higher during night-time surgery in unmatched (43.6% vs 34.1%; P<0.001) and propensity-matched analyses (43.7% vs 36.8%; P=0.029). PPCs also occurred more often in patients who underwent night-time surgery (14% vs 10%; P=0.004) in an unmatched cohort analysis, although not in a propensity-matched analysis (13.8% vs 11.8%; P=0.39). In a multivariable regression model, including patient characteristics and types of surgery and anaesthesia, night-time surgery was independently associated with a higher incidence of intraoperative AEs (odds ratio: 1.44; 95% confidence interval: 1.09–1.90; P=0.01), but not with a higher incidence of PPCs (odds ratio: 1.32; 95% confidence interval: 0.89–1.90; P=0.15).
Intraoperative adverse events and postoperative pulmonary complications occurred more often in patients undergoing night-time surgery. Imbalances in patients' clinical characteristics, types of surgery, and intraoperative management at night-time partially explained the higher incidence of postoperative pulmonary complications, but not the higher incidence of adverse events.
NCT01601223.
Introduction: Schwannomas (Schs) are benign tumor masses that rarely occur intra-abdominally and rarely reach larger diameters. When present, they occur as rare solitary nerve sheath tumors of ...peri-neural Schwann cells. Schwannoma mostly affects the nerves of the extremities, trunk, or the head and neck region. They are more common in female patients, mostly among patients between the third and fifth decade. They occur spontaneously but could also be found in association with a group of genetic autosomal dominant disorders called type 2. When present intra-abdominally, schwannomas grow slowly without significant clinical signs and symptoms. Clinical importance is presented in cases of occupying intra-abdominal space and impingement of surrounding structures, which causes intermittent pain. Only 0.5–5% of all retroperitoneal tumors are schwannomas and their malignant transformation is very rare. Case report: The authors present a case of a large intra-abdominal schwannoma in a 70-year-old female patient. She underwent CT scanning due to refractory left-sided subcostal pain, which revealed a large tumor mass in the left-sided hemiabdomen. Preoperative cytologic biopsy confirmed Sch. The patient underwent an MRI scan upon admission to our department, which revealed the origin of the tumor at the left-sided L3 level and intra-abdominal tumor spreading with the largest diameter of 25 cm. The patient underwent multidisciplinary surgical excision, confirmed by MRI scan in a period of five months postoperatively. Conclusions: Its rare presentation leads to the necessity to adequately evaluate such patients, especially to avoid any hidden diagnosis which might lead to further complications. The goal of a multidisciplinary approach should be emphasized as maintaining a good postsurgical condition without neurological deficits.
Safe and successful bioapplications of metallic nanoparticles depend on their physicochemical characteristics, in particular their surface properties. This study aimed to investigate how different ...surface functionalization of silver nanoparticles (AgNP) affect their interaction with mammalian liver cells with regard to cytotoxicity, genotoxicity and mechanism of cellular uptake. Differentially coated AgNP were prepared by surface functionalization using sodium bis(2-ethylhexyl)-sulfosuccinate (AOTAgNP), cetyltrimethylammonium bromide (CTABAgNP), poly(vinylpyrrolidone) (PVPAgNP), poly-l-lysine (PLLAgNP), and bovine serum albumin (BSAAgNP). Data showed varying toxic potential of differentially coated AgNP. All AgNP types demonstrated concentration dependent effects on cytotoxicity and genotoxicity in HepG2 cells. Cytotoxic potential of differentially coated AgNP followed the order of BSAAgNP > PLLAgNP > CTABAgNP > AOTAgNP > PVPAgNP. Exposure of HepG2 cells to non-cytotoxic concentrations (up to 10 mg Ag/L) of AgNP for 24 h induced primary DNA damage as evaluated by alkaline comet assay. The highest increase in both comet tail length and tail intensity was produced by PLLAgNP followed by AOTAgNP, while CTABAgNP appeared to be least damaging. The main uptake mechanisms of AgNP were macropinocytosis and clathrin-mediated endocytosis. The study findings contribute to the criteria that should be considered in evaluating the biocompatibility and safety of novel nanomaterials.
•Surface functionalization affects cellular toxicity and uptake of silver nanoparticles (AgNP).•All AgNP demonstrated dose response cyto- and genotoxicity in HepG2 cells.•All AgNP were taken up by macropinocytosis and clathrin-mediated endocytosis.
•Surface coating affects cytotoxicity of silver nanoparticles (AgNP) in neural stem cells.•Surface coating has impact on uptake efficiency of AgNP into neural stem cells.•All AgNP demonstrated dose ...response effects.•All AgNP were taken up by macropinocytosis.
The rapid development and widespread applications of nanotechnology necessitates the design towards safe nanoparticles. Surface structure is among the most important physicochemical characteristics of metallic nanoparticles affecting their mode of action in certain biological or environmental compartments. This study aimed to investigate how different surface coatings affect the cytotoxicity and cellular uptake of silver nanoparticles (AgNPs) in murine neural stem cells (mNSCs). Different AgNPs were prepared by stabilisation with surface coatings encompassing sodium bis(2-ethylhexyl)-sulfosuccinate (AOT), cetyltrimethylammonium bromide (CTAB), poly(vinylpyrrolidone) (PVP), poly-l-lysine (PLL), and bovine serum albumin (BSA). The obtained results revealed that AgNPs stabilized with different surface coating caused different cytotoxicity effects and internalization pattern in mNSCs. Macropinocytosis was determined as the main uptake mechanism in mNSCs for all of the tested AgNP types. These findings contribute to the overall knowledge essential to the safety assessment of novel nanomaterials.
Aminolysis of epoxides catalysed by calcium trifluoromethanesulfonate under mild reaction conditions is described. The novel method is very efficient in the synthesis of wide variety of β-amino ...alcohols with high regio- and stereoselectivity.
The novel method for aminolysis of epoxides catalysed by calcium trifluoromethanesulfonate was described (20 examples; yields 37–99%).
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