Life-threatening hyperkalaemia and multisystem toxicity following first-time exposure to cocaine

Cocaine is a drug notorious for its ability to adversely affect almost any organ in the body and cause a plethora of biochemical abnormalities secondary to its severe vasoconstrictive properties. These abnormalities are not exclusively seen in habitual users or cases of overdose, and may sometimes cause confusion as to the underlying pathology. We describe a case of a young female who presented to the Accident and Emergency department in the early hours of the morning complaining of muscle weakness following the inhalation of a small quantity of an ‘unknown substance’ the previous night. Investigations showed life-threatening hyperkalaemia with a potassium of 9.0 mmol/L, evidence of rhabdomyolysis, acute renal as well as liver failure, disseminated intravascular coagulopathy and a raised troponin of 7000 ng/L, which later peaked to 15,600 ng/L. Four days later, she became hypoxic as a result of adult respiratory distress syndrome with grossly abnormal chest X-ray appearances. Following intensive therapy, she made a dramatic recovery and was discharged from hospital 20 days from presentation. This case highlights the importance of biochemical profiling in patients presenting with possible drug use, even in the absence of significant symptoms. </jats:p

Genomic and metabolomic patterns segregate with responses to calcium and vitamin D supplementation

Inter-individual response differences to vitamin D and Ca supplementation may be under genetic control through vitamin D and oestrogen receptor genes, which may influence their absorption and/or metabolism. Metabolomic studies on blood and urine from subjects supplemented with Ca and vitamin D reveal different metabolic profiles that segregate with genotype. Genotyping was performed for oestrogen receptor 1 gene (ESR1) and vitamin D receptor gene (VDR) in fifty-six postmenopausal women. Thirty-six women were classified as low bone density as determined by a heel ultrasound scan and twenty women had normal bone density acting as 'controls'. Those with low bone density (LBD) were supplemented with oral Ca and vitamin D and were classified according to whether they were 'responders' or 'non-responders' according to biochemical results before and after therapy compared to controls receiving no supplementation. Metabolomic studies on serum and urine were done for the three groups at 0 and 3 months of therapy using NAIR spectroscopy with pattern recognition. The 'non-responder' group showed a higher frequency of polymorphisms in the ESR1 (codons 10 and 325) and VDR (Bsm1 and Tag1 compared with to the 'responders'. The wild-type genotype for Fok1 was more frequent in those with LBD (70%) compared with the control group (10%). Distinctive patterns of metabolites were displayed by NMR studies at baseline and 3 months of post-treatment, segregating responders from non-responders and controls. Identification of potential 'non-responders' to vitamin D and Ca, before therapy, based on a genomic and/or metabolomic profile would allow targeted selection of optimal therapy on an individual basis.</p

Leptin and insulin growth factor 1:diagnostic markers of the refeeding syndrome and mortality

Refeeding syndrome is difficult to diagnose since the guidelines for identifying those at risk are largely based on subjective clinical parameters and there are no predictive biochemical markers. We examined the suitability of insulin-like growth factor 1 (IGF1) and leptin as markers to identify patients at risk of the refeeding syndrome before initiation of parenteral nutrition (PN). A total of thirty-five consecutive patients referred for commencement of PN were included. Serum leptin and IGF1 were measured before starting PN. Electrolytes, liver and renal function tests were conducted before and daily for 1 week after initiating PN. The primary outcome was a decrease in phosphate 12–36 h after initiating PN. ‘Refeeding index’ (RI) was defined as leptin × IGF1 divided by 2800 to produce a ratio of 1·0 in patients who are well nourished. RI had better sensitivity (78 %; 95 % CI 40, 97 %) and specificity (78 %; 95 % CI 40, 97 %) with a likelihood ratio of 3·4, at a cut-off value of 0·19 for predicting a ≥ 30 % decrease in phosphate concentration within 12–36 h after starting PN, compared with IGF1 or leptin alone. However, IGF1 was a better predictor of mortality than either leptin or the RI. The present study is the first to derive and test the ‘RI’, and find that it is a sensitive and specific predictor of the refeeding syndrome in hospitalised patients before starting PN.</jats:p

Predicting refeeding hypophosphataemia:insulin growth factor 1 (IGF-1) as a diagnostic biochemical marker for clinical practice

Background Refeeding syndrome (RS) is a potentially fatal condition that can occur following the re-introduction of nutrition after a period of starvation. Hypophosphataemia following the reintroduction of nutrition is often the only reliable biochemical marker of RS. Refeeding index (RI) generated from baseline insulin-like growth factor-1 (IGF-1) and leptin has been proposed as a useful biochemical marker for the identification of patients at risk of developing refeeding hypophosphataemia (RH). Methods A prospective study included 52 patients referred for parenteral nutrition (PN). The sensitivity and specificity of IGF-1 measured using a sensitive assay was compared to the RI in predicting the development of RH (a ≥30% drop in PO4 during the first 36-h of PN administration). Leptin and IGF-1 were analysed on baseline samples using a quantitative enzyme-linked immunoassay. Daily blood samples were collected from all patients for routine biochemistry for the full duration of PN administration. Results High sensitivity IGF-1 measurement alone was comparable with the RI, using receiver–operating characteristic (ROC) curve analysis, with areas under the curve being 0.79 and 0.80, respectively, and superior to leptin alone (0.72) for predicting ≥30% drop in PO4. The cut-off value for IGF-1 that gave best sensitivity (91% [95% CI 75–98%]) and specificity (65% [95% CI 41–85%]) was 63.7 µg/L, with a likelihood ratio of 2.59. Conclusion Baseline IGF-1 is an objective, sensitive and specific biochemical marker in identifying patients who are at high risk of developing RH prior to PN administration and therefore may have a role in clinical practice. </jats:sec