Detection and follow-up, after partial liver resection, of the urinary paracetamol metabolites by proton NMR spectroscopy.

BACKGROUND: Combination drug therapy is often used to achieve optimal analgesia in surgery. Paracetamol can be used as one component of an analgesic regime following hepatic resection. OBJECTIVE: This study was designed to investigate paracetamol and its metabolites by proton NMR spectroscopy in patient urine and to assess whether N-acetyl-p-benzoquinone imine (NAPQI, a hepatotoxic metabolite) formation is increased after liver resection. METHOD: We studied the excretion of acetaminophen and its metabolites by 5 patients who were operated on for partial liver resection by proton NMR spectroscopy. As an intravenous infusion 1 g of paracetamol was given over 15 min every 6 h during 48 h. The first injection was given in the operating theatre after liver resection was completed. Urine samples were collected before injection (T1) and 24 and 48 h after the first injection (T2 and T3); the samples were frozen and kept at -20°C up to the analysis by NMR spectroscopy. RESULTS: Metabolites of the paracetamol were detected for all patients. Among the discerned metabolites, 4 were identified as metabolites of paracetamol: paracetamol glucuronide, paracetamol sulfate, N-acetyl-L-cysteinyl paracetamol (metabolite of NAPQI) and paracetamol. Their ratios, respectively, were: 46-82.9, 12.6-30.0, 0.5-5.5 and 1.43-3.54%. CONCLUSION: This study showed that there was no increase in the formation of toxic metabolite (NAPQI) after treatment with paracetamol in these few cases of liver resections. A larger study is necessary to confirm these results.

Face mask ventilation in edentulous patients: a comparison of mandibular groove and lower lip placement.

BACKGROUND: In edentulous patients, it may be difficult to perform face mask ventilation because of inadequate seal with air leaks. Our aim was to ascertain whether the "lower lip" face mask placement, as a new face mask ventilation method, is more effective at reducing air leaks than the standard face mask placement. METHODS: Forty-nine edentulous patients with inadequate seal and air leak during two-hand positive-pressure ventilation using the ventilator circle system were prospectively evaluated. In the presence of air leaks, defined as a difference of at least 33% between inspired and expired tidal volumes, the mask was placed in a lower lip position by repositioning the caudal end of the mask above the lower lip while maintaining the head in extension. The results are expressed as mean +/- SD or median (25th-75th percentiles). RESULTS: Patient characteristics included age (71 +/- 11 yr) and body mass index (24 +/- 4 kg/m2). By using the standard method, the median inspired and expired tidal volumes were 450 ml (400-500 ml) and 0 ml (0-50 ml), respectively, and the median air leak was 400 ml (365-485 ml). After placing the mask in the lower lip position, the median expired tidal volume increased to 400 ml (380-490), and the median air leak decreased to 10 ml (0-20 ml) (P < 0.001 vs. standard method). The lower lip face mask placement with two hands reduced the air leak by 95% (80-100%). CONCLUSIONS: In edentulous patients with inadequate face mask ventilation, the lower lip face mask placement with two hands markedly reduced the air leak and improved ventilation.

Use of nuclear magnetic resonance spectroscopy to assess renal dysfunction after hypertonic-hyperoncotic resuscitation in rats.

BACKGROUND: The aim of this study was to evaluate the renal tolerance of a hypertonic-hyperoncotic solution (HHS) administration during uncontrolled hemorrhagic shock (UHS). METHODS: UHS was produced in rats by a preliminary bleed followed by tail amputation. Hydroxyethylstarch (HHS) 200/0.5 6% in NaCl 7.2% was administered to the HHS groups (n = 20) and normal saline (NS) to the NS group (n = 20). Infusion rates were adjusted to prevent mean arterial pressure (MAP) from falling either below 40 mm Hg in the HHS40 (n = 10) and NS40 groups (n = 10), or below 80 mm Hg in the HHS80 (n = 10) and NS80 groups (n = 10). Data obtained were compared with a sham group and a no resuscitation (NR) group. Nephrotoxicity was evaluated by nuclear magnetic resonance analysis in urine samples. RESULTS: Survival was 60% in the NS40 group and 40% in the NS80 group, 70% in the HHS40 group, and 60% in the HHS80 group (p = not significant). Within and between target groups of 40 mm Hg MAP and 80 mm Hg MAP, there was no significant difference in survival. The mean values of renal metabolites to creatinine (ct) ratios were not significantly different among the six groups. Principal component analysis showed that the HHS80 group was characterized by an increase in allantoin/ct and urea/ct ratios demonstrating acute renal dysfunction and failure of nitrogen metabolism. CONCLUSION: In prolonged UHS, an infusion of HHS may not increase the rate of survival. HHS infusion in normotensive resuscitation appears to be associated with renal toxicity.

Aminoglycoside and glycopeptide renal toxicity in intensive care patients studied by proton magnetic resonance spectroscopy of urine.

OBJECTIVE: Aminoglycoside and glycopeptide antibiotics are responsible for renal toxicity. In most cases, the nephrotoxicity is limited to a reversible tubular injury, but an acute and sustained renal failure may occur. The aim of our study was to explore the renal function of patients given these antimicrobial agents with proton magnetic resonance spectroscopy of urine. This technique is able to detect, in urine samples, a wide range of metabolites reflecting renal tubular function. The variables assessed by magnetic resonance spectroscopy were compared with the routine markers of renal function: creatinine, urea, and 24-hr urine volume. DESIGN: Prospective clinical study. SETTING: Intensive care unit. PATIENTS: All patients in an intensive care unit receiving an aminoglycoside and/or a glycopeptide were included in the study if they presented with signs of renal dysfunction. All experiments were performed on urine samples collected for the routine follow-up of these patients. INTERVENTION: Proton spectra were acquired with water suppression, and the peak intensity of each metabolite was reported in relationship to the intensity of the creatinine peak. MEASUREMENTS AND MAIN RESULTS: The ratio values obtained by magnetic resonance spectroscopy were compared with the values of creatininemia and blood urea obtained routinely by biochemistry and with the value of the 24-hr urine volume by logistic regression and general linear models. This statistical analysis showed that the ratio of dimethylamine to creatinine was highly correlated with creatininemia. CONCLUSIONS: Dimethylamine is an osmolyte released from the medullar region of the kidney. Thus, our study demonstrated that nephrotoxicity from aminoglycosides and glycopeptides is not limited to proximal tubular toxicity but also may involve the medullar region (Henle loop and collecting duct) of the nephron.