Efficacy and safety of high-flow nasal cannula therapy in elderly patients with acute respiratory failure.

INTRODUCTION: To assess the efficacy and safety of high-flow nasal cannula (HFNC) in elderly patients with acute respiratory failure (ARF) not due to COVID-19, refractory to treatment with conventional oxygen therapy and/or intolerant to noninvasive ventilation (NIV) or continuous positive airway pressure (CPAP) and without criteria for admission to intensive care units (ICU). METHODS: Prospective observational study of patients with ARF treated with HFNC who presented clinical and arterial blood gas deterioration after 24 h of medical treatment and oxygenation by conventional systems. The degree of dyspnoea, gas exchange parameters (arterial O2 pressure/inspired O2 fraction ratio (PaO2/FiO2); oxygen saturation measured by oximetry/ inspired fraction of oxygen (Sp02/Fi02), ROX index), degree of patient tolerance and mortality were evaluated. These were measured at discharge from the emergency department (ED), 24 h after treatment with conventional oxygenation and 60, 120 min and 24 h after initiation of HFNC. The results were analyzed for all patients as a whole and for patients with hypercapnia (arterial carbon dioxide tension (PaCO2) < 45 mmHg) separately. RESULTS: 200 patients were included in the study between November 2019 and November 2020, with a mean age of 83 years, predominantly women (61.9%), obese (Body Mass Index (BMI) 31.1), with high comorbidity (Charlson index 4) and mild-moderate degree of dependence (Barthel 60). A number of 128 patients (64%) were hypercapnic. None had respiratory acidosis (pH 7.39). Evaluation at 60 min, 120 min and 24 h showed significant improvement in all patients and in the subgroup of hypercapnic patients with respect to baseline parameters in respiratory rate (RR), dyspnoea, ROX index, PaO2/FiO2, SpO2/FiO2 and patient comfort. No changes in PaCO2 or level of consciousness were observed. HFNC was well tolerated. Ten patients (5%) died due to progression of the disease causing ARF. CONCLUSIONS: HFNC is an effective and safe alternative in elderly patients with ARF not due to COVID-19, refractory to treatment with conventional oxygen therapy and/or intolerant to NIV or CPAP and without criteria for admission to ICU.

Population pharmacokinetics of oxaliplatin after intraperitoneal administration with hyperthermia in Wistar rats.

BACKGROUND: The evaluation of the efficacy and toxicity of hyperthermic intraoperative peritoneal chemotherapy presents some difficulties, due in part to the lack of information about the pharmacokinetic behavior of the drugs administered in this procedure. The aim of this study was to characterize the population pharmacokinetics of hyperthermic intraoperative peritoneal oxaliplatin in Wistar rats and to evaluate the effect of treatment-related covariates dose, instillation time and temperature on the pharmacokinetic parameters. METHODS: Oxaliplatin peritoneal and plasma concentrations from 37 rats treated by either intravenous or intraperitoneal oxaliplatin administrations under different instillation times, temperatures and doses were analyzed according to a population pharmacokinetic approach using the software NONMEM V7.3®. RESULTS: Intraperitoneal (n = 115) and plasma (n = 263) concentrations were successfully described according to a two-compartment model with first order absorption. No significant effect of dose, temperature and instillation time on pharmacokinetic parameters was found. However, an abrupt decrease in the elimination process was observed, reflected in the structural pharmacokinetic model through a modification in clearance. The typical parameters values and the interindividual variability (CV %) in clearance, central and peripheral volume of distribution were 3.25 mL/min (39.1%), 53.6 mL (37.8%) and 54.1 mL (77.3%), respectively. Clearance decreased to 0.151 mL/min (39.1%) when the instillation was still ongoing, at 31.4 min. One of the possible reasons behind the clearance decrease would be an alteration of renal function due to surgery and/or hyperthermia. CONCLUSIONS: This study described the deterioration of the drug elimination process due to the procedure, and estimated the time at which this deterioration is most likely to occur. In addition, dose, instillation time and temperature had no influence in the PK parameters.

Mammalian Target of Rapamycin Inhibitor Monotherapy: Efficacy in Renal Transplantation.

BACKGROUND: Calcineurin inhibitors (CNI) have failed to improve long-term outcomes in renal transplantation. Anti-proliferative and anti-angiogenic effects of mammalian target of rapamycin inhibitors (m-TOR) without nephrotoxicity could improve long-term survival in selected transplant recipients. METHODS: We examined the evolution of 98 low-immunological risk renal transplant recipients on m-TOR monotherapy: 7 patients had induction without CNI and 91 were switched to m-TOR at 12 (p25-p75: 4-36) months after transplant. RESULTS: Median follow-up time was 46 (p25-p75: 28.5-72.0) months. Fifteen recipients dropped out of the study (15.3%): 8 patients (8.2%) had to change their immunosuppressive treatment because of complications and 7 (7.1%) lost their grafts as a result of chronic rejection (4 cases) or death with a functioning graft (3 cases). At the end of follow-up, 83 of 98 (84.6%) recipients remained on monotherapy. The rates of recipient and graft survivals were 100% and 98.8% at 2 years and 96.9% and 93.5% at 4 years; the percentages of patients on monotherapy after 2 and 4 years were 95.2% and 85.2%, respectively. Renal function improved significantly and proteinuria decreased but not significantly. Those patients switched to m-TOR significantly received more erythropoietin, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and hypotensive agents than before starting m-TOR, whereas there were no significant changes related to the use of statins, body weight, or percentage of diabetic patients. No case of non-compliance was reported. CONCLUSIONS: This study supports the safety and efficacy of monotherapy with m-TOR in selected renal transplant recipients.

[Gastric enteral intolerance in mechanically ventilated patients with traumatic cerebral lesion]. / Intolerancia enteral gástrica en pacientes con lesión cerebral de origen traumático, ventilados mecánicamente.

OBJECTIVE: To check the correlation between gastric intolerance and hypertension intracranial pressure and their association with the clinical parameters and severity indexes in patients with severe head injury (HI); to evaluate the advantages of transpyloric feeding. DESIGN: Prospective and observational clinical study. SETTING: Intensive Care Unit (ICM) of a General University Hospital. PATIENTS AND PARTICIPANTS: 25 brain injured patients requiring sedation, mechanical ventilation and hypertensión intracranial monitoring. INTERVENTIONS: Analysis of the incidence of delayed gastric emptying (area under the curve (AUC60)) and of gastrointestinal intolerance; study of their correlation with hypertension intracranial, severity indexes and sedative medication administered; evaluation of the alternative effectiveness of transpyloric feeding. MEASUREMENTS AND RESULTS: 44% of the patients showed GI, which was measured by means of the paracetamol test (AUC60). The sedative medication was related to IG (p < 0.005), HIC (p < 0.01) and AUC60 (p < 0.01). Of the severity indexes, there was a correlation between Glasgow Coma Score and AUC60 (p < 0.01); the Marshall score HIC (p < 0.005) and AUC60 (p < 0.01). Of the quantitative variables, we found a correlation between HIC and IG (p < 0.001), HIC and pneumonia (p < 0.01), IG as well pneumonia (p < 0.001), and AUC60 (p < 0.001) and AUC60 and pneumonia (p < 0.05). CONCLUSIONS: Enteral intolerance in patients with HI is due to delayed gastric emptying (DGE) which is proportional to the severity of the head injury and to the intensity of the systemic response. The high incidence of GI makes transpyloric feeding advisable in order to attain the nutritional objective and to reduce the risk of aspirative nosocomial pneumonia.

Kinetic study of acamprosate absorption in rat small intestine.

Acamprosate (calcium bis acetyl-homotaurine), a homotaurine derivative, a structural analogue of gamma-aminobutyric acid (GABA) and an upper homologue of taurine, is a relatively new drug used to prevent relapse in weaned alcoholics. When administered orally as enteric-coated tablets at relatively high doses, this drug has a bioavailability of about 11%; however, the intestinal absorption mechanism has not been studied in depth. The present study was therefore planned to characterize the intestinal transport of acamprosate in the rat and the effect of chronic alcohol treatment on this process, quantifying its kinetic parameters and investigating possible inhibitors. Using an in vitro technique, acamprosate absorption was measured in the rat intestine from three different groups: alcohol group [fed a liquid diet containing 5% (w/v) ethanol for 4 weeks], isocaloric pair-fed control, and a solid diet group. Intestinal acamprosate absorption was found to occur mainly by passive diffusion with a diffusive permeability of 0.213+/-0.004 cm/h in control pair-fed animals, 0.206+/-0.001 cm/h in animals receiving chronic alcohol treatment, and 0.193+/-0.001 cm/h in the solid diet group. Inhibition studies showed that at a 10(-3) M acamprosate concentration, some compounds such as GABA, taurine, proline, and glycine at 40 mM each did not affect acamprosate transport. Nevertheless, when a lower concentration of the drug (10(-4) M) was assayed, a significant reduction of acamprosate transport in the presence of taurine or GABA 40 mM was found. These results suggest that acamprosate in the rat jejunum, could be transported, in part, by a carrier system. Further experiments using different concentrations of taurine (10, 20, and 80 mM) showed that the maximum inhibition (32%) is achieved at 20 mM of taurine. These latter results suggest that acamprosate and taurine share, at least, an intestinal carrier system in rat jejunum. From the above results, it can be concluded that there are probably two pathways involved in the intestinal absorption of acamprosate: passive diffusion and mediated transport, with the former being predominant. Moreover, neither chronic ethanol intake nor the type of diet seems to alter the intestinal absorption of the drug.