Oral 5-aminolevulinic acid administration before transurethral resection of bladder tumor induces perioperative nausea and vomiting.

BACKGROUND: The efficacy of photodynamic diagnosis using 5-aminolevulinic acid during transurethral resection of bladder tumors has been demonstrated, albeit with limited information regarding its side effects. This study aimed to clarify the impact of oral 5-aminolevulinic acid on perioperative nausea and vomiting (NV) for the first time in a real-world clinical practice setting. METHODS: Patients who underwent transurethral surgery at Kagawa University between April 2017 and March 2020 were included. Perioperative NV and antiemetic use status were prospectively assessed and compared between the patients who received oral 5-aminolevulinic acid and those who did not. Additionally, univariate and multivariate analyses were performed for predicting postoperative nausea and vomiting. RESULTS: Of 214 patients, 74 (34.6%) received oral 5-aminolevulinic acid preoperatively. The proportions of preoperative NV and antiemetic use in the patients who received 5-aminolevulinic acid were 9.5% and 4.1%, respectively, and higher than in those who did not (0% and 0%; P < 0.01 and P = 0.04, respectively). Postoperative NV (25.7%) and antiemetics use (8.0%) ratios in the patients who received 5-aminolevulinic acid were significantly different from those in the non-users group (3.6% and 2.1%, P < 0.01 and P < 0.01, respectively). Although no differences in risk factors were found for postoperative NV between the two groups, multivariate analyses indicated 5-aminolevulinic acid use as an independent predictive factor for postoperative NV (odds ratio, 11.5; 95% confidence interval, 3.98-33.3; P < 0.01). CONCLUSIONS: Our study clearly showed that oral administration of 5-aminolevulinic acid was associated with perioperative NV even without risk factors, highlighting the need for addressing its application.

Physiological Modeling of Concentration-Effect Relationship for Nondepolarizing Neuromuscular Blocking Drugs.

This paper reports modeling of physiological processes of neuromuscular transmission considering effects of nondepolarizing neuromuscualr blocking drugs (NDNBs) used during general anesthesia. NDNBs are considered to act by interacting with acetylcohine receptors located at pre- and post-junctional sites. This paper proposes an extension of the standard model of synaptic depression used in the field of neuroscience to describe the pre-junctional effect of NDNBs. The extended model is then combined with a previously proposed model of the post-junctional effect to simulate the whole process of neuromuscular transmission. The derived model can be used to predict pharmacologic relationship between the drug concentration and its actual effect of NDNBs. Specifically, the model firstly enables the estimation of Post-tetanic Count (PTC), a clinically used monitoring measure for deep neuromuscular blockade (NMB). The effectiveness of the derived model is discussed by comparing simulation results with clinical data obtained from a patient undergoing a surgical operation.

Guanylyl Cyclase A in Both Renal Proximal Tubular and Vascular Endothelial Cells Protects the Kidney against Acute Injury in Rodent Experimental Endotoxemia Models.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Natriuretic peptides are used, based on empirical observations, in intensive care units as antioliguric treatments. We hypothesized that natriuretic peptides prevent lipopolysaccharide-induced oliguria by activating guanylyl cyclase A, a receptor for natriuretic peptides, in proximal tubules and endothelial cells. METHODS: Normal Sprague-Dawley rats and mice lacking guanylyl cyclase A in either endothelial cells or proximal tubular cells were challenged with lipopolysaccharide and assessed for oliguria and intratubular flow rate by intravital imaging with multiphoton microscopy. RESULTS: Recombinant atrial natriuretic peptide efficiently improved urine volume without changing blood pressure after lipopolysaccharide challenge in rats (urine volume at 4 h, lipopolysaccharide: 0.6 ± 0.3 ml · kg · h; lipopolysaccharide + fluid resuscitation: 4.6 ± 2.0 ml · kg · h; lipopolysaccharide + fluid resuscitation + atrial natriuretic peptide: 9.0 ± 4.8 ml · kg · h; mean ± SD; n = 5 per group). Lipopolysaccharide decreased glomerular filtration rate and slowed intraproximal tubular flow rate, as measured by in vivo imaging. Fluid resuscitation restored glomerular filtration rate but not tubular flow rate. Adding atrial natriuretic peptide to fluid resuscitation improved both glomerular filtration rate and tubular flow rate. Mice lacking guanylyl cyclase A in either proximal tubules or endothelium demonstrated less improvement of tubular flow rate when treated with atrial natriuretic peptide, compared with control mice. Deletion of endothelial, but not proximal tubular, guanylyl cyclase A augmented the reduction of glomerular filtration rate by lipopolysaccharide. CONCLUSIONS: Both endogenous and exogenous natriuretic peptides prevent lipopolysaccharide-induced oliguria by activating guanylyl cyclase A in proximal tubules and endothelial cells.