20 research outputs found

    An unconscious man with profound drug-induced hypoglycaemia

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    Introduction: Hypoglycaemia has been reported as an unusual complication of tramadol use and in a few cases of tramadol poisoning, but the exact mechanism is not known. Case description: An ambulance crew was dispatched to an unconscious 46-year old man. A glucometer point-of-care measurement revealed a profound hypoglycaemia (1.9 mmol/L). Treatment with intravenous glucose was started and the patient was transported to the hospital. The patient had several episodes of pulseless electrical activity requiring cardiopulmonary resuscitation in the ambulance and upon arrival in the hospital. Despite continuous glucose infusion the hypoglycaemia was difficult to correct during the next few hours and the patient developed hypokalaemia. Further investigation to identify the cause of hypoglycaemia revealed that insulin and C-peptide were inappropriately raised. A toxicological investigation revealed the presence of tramadol and its metabolites in lethal concentrations. Also acetaminophen, ibuprofen and lormetazepam were present. Ethanol screening was negative (< 0.1 g/L) and no sulfonylurea were detected. The patient developed multiple organ failure, but eventually recovered. What happened: The hypoglycaemia was caused by inappropriate stimulation of insulin secretion in a patient intoxicated with tramadol. The sudden hypokalaemia was caused by a massive intracellular shift of potassium in response to the hyperinsulinemia, triggered by the intravenous administration of glucose. Main lesson: To our knowledge, we are the first to document a significant rise in endogenous insulin production in a hypoglycaemic patient presenting with tramadol intoxication. Our observation suggests that hyperinsulinemia could be the cause of the hypoglycaemia associated with tramadol use

    Analytical performance of eight enzymatic assays for ethanol in serum evaluated by data from the Belgian external quality assessment scheme

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    Abstract Objectives Fast and reliable ethanol assays analysis are used in a clinical context for patients suspected of ethanol intoxication. Mostly, automated systems using an enzymatic reaction based on ethanol dehydrogenase are used. The manuscript focusses on the evaluation of the performance of these assays. Methods Data included 30 serum samples used in the Belgian EQA scheme from 2019 to 2021 and concentrations ranged from 0.13 to 3.70 g/L. A regression line between target concentrations and reported values was calculated to evaluate outliers, bias, variability and measurement uncertainty. Results A total of 1,611 results were taken into account. Bias was the highest for Alinity c over the whole concentration range and the lowest for Vitros for low concentrations and Cobas 8000 using the c702 module for high concentrations. The Architect and Cobas c501/c502 systems showed the lowest variability over the whole concentration range. Highest variability was observed for Cobas 8000 using the 702 module, Thermo Scientific and Alinity c. Cobas 8000 using the c702 module showed the highest measurement uncertainty for lower concentrations. For higher concentrations, Alinity c, Thermo Scientific and Vitros were the methods with the highest measurement uncertainty. Conclusions The bias of the enzymatic techniques is nearly negligible for all methods except Alinity c. Variability differs strongly between measurement procedures. This study shows that the Alinity c has a worse measurement uncertainty than other systems for concentrations above 0.5 g/L. Overall, we found the differences in measurement uncertainty to be mainly influenced by the differences in variability

    Hydrogel impregnation of bone chips allows prolonged cefazolin release

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    Introduction To prevent infections after orthopedic surgery, intravenous antibiotics are administered perioperatively. Cefazolin is widely used as the prophylactic antibiotic of choice. Systemic antibiotic therapy may however be less effective in longstanding surgery where bone allografts are used. Bone chips have been shown to be an effective carrier for certain types of antibiotics. Bone allografts impregnated with antibiotics may therefore provide the necessary local antibiotic levels for prophylaxis. To be efficient, a prolonged release from these bonechips is required. In contrast to vancomycin, for which prolonged release has clearly been proven effective from Osteomycin®, a commercially available impregnated bone allograft, no prolonged release bone chip preparations have been described so far for cefazolin. We developed a protocol to bind cefazolin in the porous structure of bone chips by means of a hydrogel composed of proteins naturally present in the human body. Material and methods Three types of bone chips were evaluated: fresh frozen, decellularized frozen and decellularized lyophilized. Bone chips were incubated with 20 mg/ml cefazolin or treated with liquid hydrogel containing either 1 mg/ml fibrin or 1 mg/ml collagen and 20 mg/ml cefazolin. The cefazolin hydrogel was distributed in the porous structure by short vacuum treatment. Bone chips with cefazolin but without hydrogel were either incubated for 20 min- 4h or also treated with vacuum. Cefazolin elution of bone chips was carried out in fetal bovine serum and analyzed by Ultra Performance Liquid Chromatography – Diode Array Detection. Results Soaking of bone chips without hydrogel resulted in a quick release of cefazolin, which was limited to 4 hours. When vacuum was applied elution of >1 µg/ml cefazolin was measured for up to 36 hours. Combination with collagen hydrogel resulted in a higher cefazolin concentration released at 24 hours (3.9 vs 0.3 µg/ml), but not in a prolonged release. However, combination of decellularized frozen bone chips with fibrin hydrogel resulted in an initial release of 533 µg/ml followed by a gradual decline reaching the minimal inhibitory concentration for S. aureus at 72 hours (1.7 µg/ml), while not measurable anymore after 92 hours. Discussion Processed bone chips with hydrogel-cefazolin showed a markedly prolonged cefazolin release. When combined with a fibrin hydrogel, high initial peak levels of cefazolin were obtained, followed by a decreasing release over the following three days. This elution profile is desirable, since high initial levels are important to maximize anti-bacterial action whereas low levels of antibiotic for a limited time may stimulate osteogenesis. It is important that antibiotic release is ending after a few days as prolonged low levels of antibiotics are not clinically helpful and may lead to antibiotic resistance. Further preclinical studies are warranted to show effectiveness of hydrogel-cefazolin impregnated bone chips.status: publishe

    Hydrogel impregnation of bone chips allows prolonged cefazolin release

    No full text
    Introduction To prevent infections after orthopedic surgery, intravenous antibiotics are administered perioperatively. Cefazolin is widely used as the prophylactic antibiotic of choice. Systemic antibiotic therapy may however be less effective in longstanding surgery where bone allografts are used. Bone chips have been shown to be an effective carrier for certain types of antibiotics. Bone allografts impregnated with antibiotics may therefore provide the necessary local antibiotic levels for prophylaxis. To be efficient, a prolonged release from these bonechips is required. In contrast to vancomycin, for which prolonged release has clearly been proven effective from Osteomycin®, a commercially available impregnated bone allograft, no prolonged release bone chip preparations have been described so far for cefazolin. We developed a protocol to bind cefazolin in the porous structure of bone chips by means of a hydrogel composed of proteins naturally present in the human body. Material and methods Three types of bone chips were evaluated: fresh frozen, decellularized frozen and decellularized lyophilized. Bone chips were incubated with 20 mg/ml cefazolin or treated with liquid hydrogel containing either 1 mg/ml fibrin or 1 mg/ml collagen and 20 mg/ml cefazolin. The cefazolin hydrogel was distributed in the porous structure by short vacuum treatment. Bone chips with cefazolin but without hydrogel were either incubated for 20 min- 4h or also treated with vacuum. Cefazolin elution of bone chips was carried out in fetal bovine serum and analyzed by Ultra Performance Liquid Chromatography – Diode Array Detection. Results Soaking of bone chips without hydrogel resulted in a quick release of cefazolin, which was limited to 4 hours. When vacuum was applied elution of >1 µg/ml cefazolin was measured for up to 36 hours. Combination with collagen hydrogel resulted in a higher cefazolin concentration released at 24 hours (3.9 vs 0.3 µg/ml), but not in a prolonged release. However, combination of decellularized frozen bone chips with fibrin hydrogel resulted in an initial release of 533 µg/ml followed by a gradual decline reaching the minimal inhibitory concentration for S. aureus at 72 hours (1.7 µg/ml), while not measurable anymore after 92 hours. Discussion Processed bone chips with hydrogel-cefazolin showed a markedly prolonged cefazolin release. When combined with a fibrin hydrogel, high initial peak levels of cefazolin were obtained, followed by a decreasing release over the following three days. This elution profile is desirable, since high initial levels are important to maximize anti-bacterial action whereas low levels of antibiotic for a limited time may stimulate osteogenesis. It is important that antibiotic release is ending after a few days as prolonged low levels of antibiotics are not clinically helpful and may lead to antibiotic resistance. Further preclinical studies are warranted to show effectiveness of hydrogel-cefazolin impregnated bone chips.status: publishe

    Establishing age/sex related serum creatinine reference intervals from hospital laboratory data based on different statistical methods

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    BACKGROUND: This is a retrospective study on a large hospital database to establish age- and sex-related mean values and reference ranges for serum creatinine (Scr), obtained with an IDMS-traceable, enzymatic method, in a Caucasian population. METHODS: The database was filtered for unique entries to reduce the presence of correlated and pathological data. Three different statistical methods, a non-parametric method, the Bhattacharya procedure and a non-linear fit of the cumulative Gaussian distribution were used to estimate the serum creatinine-age dependency for men and women, from birth till 100 years of age. RESULTS: Scr increases with age, equal for boys and girls, up to 14 years and with a much steeper slope for boys than for girls between 14 and 20 years. We show that the Scr-age pattern is constant between 20 and 70 years with a mean of 0.90 mg/dL [0.63-1.16 mg/dL] for men and 0.70 mg/dL [0.48-0.93 mg/dL] for women. Above 70, Scr starts to slowly increase again. CONCLUSIONS: Indirect methods confirm the available reference intervals from healthy-volunteer studies and add information on age-periods not covered by these studies. As such, indirect methods can be used complementary to healthy-volunteer studies.status: publishe
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