Evaluation of DNA damage and lipoperoxidation of propofol in patients undergoing elective surgery

Inhaled anaesthetics have been studied regarding their genotoxic and mutagenic potential in vivo. Propofol differs from volatile anaesthetics because it does not show mutagenic effects and it has been reported to be an antioxidant. However, there are no studies with propofol and genotoxicity in vivo. The study aimed to evaluate the hypothesis that propofol is not genotoxic and it inhibits lipid peroxidation [malondialdehyde (MDA)] in patients undergoing propofol anaesthesia. ASA physical status I patients scheduled for elective surgery, lasting at least 90 min, were enrolled in this study. Initially, the estimated plasma concentration of propofol was targeted at 4 microg ml(-1) and then maintained at 2-4 microg ml(-1) until the end of surgery. Haemodynamic data were determined at baseline (before premedication) and in conjunction with target-controlled infusion of propofol: after tracheal intubation, 30, 60 and 90 min after anaesthesia induction and at the end of the surgery. Venous blood samples were collected at baseline, after tracheal intubation, at the end of the surgery and on the postoperative first day for evaluating DNA damage in white blood cells (WBCs), by comet assay, and MDA levels. Haemodynamic data did not differ among times. No statistically significant differences were observed for the levels of DNA damage in WBCs, nor in plasma MDA, among the four times. Propofol does not induce DNA damage in WBCs and does not alter MDA in plasma of patients.

Isoflurane and propofol contribute to increasing the antioxidant status of patients during minor elective surgery: a randomized clinical study

Isoflurane is a volatile halogenated anesthetic used especially for anesthesia maintenance whereas propofol is a venous anesthetic utilized for anesthesia induction and maintenance, and reportedly an antioxidant. However, there are still controversies related to isoflurane-induced oxidative stress and it remains unanswered whether the antioxidant effects occur in patients under propofol anesthesia.Taking into account the importance of better understanding the role of anesthetics on oxidative stress in anesthetized patients, the present study was designed to evaluate general anesthesia maintained with isoflurane or propofol on antioxidant status in patients who underwent minimally invasive surgeries.We conducted a prospective randomized trial in 30 adult patients without comorbidities who underwent elective minor surgery (septoplasty) lasting at least 2 h admitted to a Brazilian tertiary hospital.The patients were randomly allocated into 2 groups, according to anesthesia maintenance (isoflurane, n = 15 or propofol, n = 15). Peripheral blood samples were drawn before anesthesia (baseline) and 2-h after anesthesia induction.The primary outcomes were to investigate the effect of either isoflurane or propofol anesthesia on aqueous plasma oxidizability and total antioxidant performance (TAP) by fluorometry as well as several individual antioxidants by high-performance liquid chromatography. As secondary outcome, oxidized genetic damage (7,8-dihydro-8-oxoguanine, known as 8-oxo-Gua) was investigated by the comet assay.Both anesthesia techniques (isoflurane or propofol) for a 2-h period resulted in a significant decrease of plasma α-tocopherol, but not other antioxidants including uric acid, carotenoids, and retinol (P > 0.05). Propofol, in contrast to isoflurane anesthesia, significantly increased (P < 0.001) anti-inflammatory/antioxidant plasma γ-tocopherol concentration in patients. Both anesthesia types significantly enhanced hydrophilic antioxidant capacity and TAP, with no significant difference between them, and 8-oxo-Gua remained unchanged during anesthesia in both groups. In addition, both anesthetics showed antioxidant capacity in vitro.This study shows that anesthesia maintained with either propofol or isoflurane increase both hydrophilic and total antioxidant capacity in plasma, but only propofol anesthesia increases plasma γ-tocopherol concentration. Additionally, both types of anesthetics do not lead to oxidative DNA damage in patients without comorbidities undergoing minimally invasive surgery.

Avaliação do desempenho de dois monitores oscilométricos portáteis na estimativa da pressão arterial direta em gatos anestesiados com isofluorano

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Prone positioning attenuates TNF-alpha production in rabbits with lung injury under protective conventional mechanical ventilation (CMV)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Burrow ventilation and associated porewater irrigation by the polychaete Marenzelleria viridis

Burrow ventilation of benthic infauna generates water currents that irrigate the interstices of the sediments surrounding the burrow walls. Such activities have associated effects on biogeochemical processes affecting ultimately important ecosystem processes. In this study, the ventilation and irrigation behavior of Marenzelleria viridis, an invasive polychaete species in Europe, was analyzed using different approaches. M. viridis showed to perform two types of ventilation: (1) muscular pumping of water out of the burrow and (2) cilia pumping of water into the burrow. Flowmeter measurements presented muscular pumping in time averaged rates of 0.15 ml min(-1). Oxygen needle electrodes positioned above the burrow openings revealed that muscular undulation of the worm body pumps anoxic water out of the burrow. On the other hand, microscope observations of the animal showed that ventilation of oxygen-rich water in the burrow occurs by ciliary action. The volume of water irrigated by M. viridis appears to vary linearly within the first 24 h incubation, with rates ranging from 0.003 to 0.01 ml min(-1). From those rates we could estimate that the time averaged rate of cilia ventilation should be about 0.16 ml min(-1). Since the cilia pumping into the burrow occurs in periods of 24 +/- 12 min and at 50-70% of the measured time, considerable amounts of water from deeper sediments may percolate upwards to the sediment surface. This water is rich in reduced compounds and nutrients and may have important associated ecological implications in the ecosystem (e.g. affecting redox conditions, organic matter degradation, benthic recruitment and primary production). (C) 2010 Elsevier B.V. All rights reserved.

Replacement of fentanyl infusion by enteral methadone decreases the weaning time from mechanical ventilation: a randomized controlled trial

Introduction: Patients undergoing mechanical ventilation (MV) are frequently administered prolonged and/or high doses of opioids which when removed can cause a withdrawal syndrome and difficulty in weaning from MV. We tested the hypothesis that the introduction of enteral methadone during weaning from sedation and analgesia in critically ill adult patients on MV would decrease the weaning time from MV. Methods: A double-blind randomized controlled trial was conducted in the adult intensive care units (ICUs) of four general hospitals in Brazil. The 75 patients, who met the criteria for weaning from MV and had been using fentanyl for more than five consecutive days, were randomized to the methadone (MG) or control group (CG). Within the first 24 hours after study enrollment, both groups received 80% of the original dose of fentanyl, the MG received enteral methadone and the CG received an enteral placebo. After the first 24 hours, the MG received an intravenous (IV) saline solution (placebo), while the CG received IV fentanyl. For both groups, the IV solution was reduced by 20% every 24 hours. The groups were compared by evaluating the MV weaning time and the duration of MV, as well as the ICU stay and the hospital stay. Results: Of the 75 patients randomized, seven were excluded and 68 were analyzed: 37 from the MG and 31 from the CG. There was a higher probability of early extubation in the MG, but the difference was not significant (hazard ratio: 1.52 (95% confidence interval (CI) 0.87 to 2.64; P = 0.11). The probability of successful weaning by the fifth day was significantly higher in the MG (hazard ratio: 2.64 (95% CI: 1.22 to 5.69; P < 0.02). Among the 54 patients who were successfully weaned (29 from the MG and 25 from the CG), the MV weaning time was significantly lower in the MG (hazard ratio: 2.06; 95% CI 1.17 to 3.63; P < 0.004). Conclusions: The introduction of enteral methadone during weaning from sedation and analgesia in mechanically ventilated patients resulted in a decrease in the weaning time from MV.

Low pressure support changes the rapid shallow breathing index (RSBI) in critically ill patients on mechanical ventilation

Background: The rapid shallow breathing index (RSBI) is the most widely used index within intensive care units as a predictor of the outcome of weaning, but differences in measurement techniques have generated doubts about its predictive value. Objective: To investigate the influence of low levels of pressure support (PS) on the RSBI value of ill patients. Method: Prospective study including 30 patients on mechanical ventilation (MV) for 72 hours or more, ready for extubation. Prior to extubation, the RSBI was measured with the patient connected to the ventilator (Drager (TM) Evita XL) and receiving pressure support ventilation (PSV) and 5 cmH(2)O of positive end expiratory pressure or PEEP (RSBI_MIN) and then disconnected from the VM and connected to a Wright spirometer in which respiratory rate and exhaled tidal volume were recorded for 1 min (RSBI_ESP). Patients were divided into groups according to the outcome: successful extubation group (SG) and failed extubation group (FG). Results: Of the 30 patients, 11 (37%) failed the extubation process. In the within-group comparison (RSBI_MIN versus RSBI_ESP), the values for RSBI_MIN were lower in both groups: SG (34.79 +/- 4.67 and 60.95 +/- 24.64) and FG (38.64 +/- 12.31 and 80.09 +/- 20.71; p<0.05). In the between-group comparison, there was no difference in RSBI_MIN (34.79 +/- 14.67 and 38.64 +/- 12.31), however RSBI_ESP was higher in patients with extubation failure: SG (60.95 +/- 24.64) and FG (80.09 +/- 20.71; p<0.05). Conclusion: In critically ill patients on MV for more than 72h, low levels of PS overestimate the RSBI, and the index needs to be measured with the patient breathing spontaneously without the aid of pressure support.

Pentraxin 3 accelerates lung injury in high tidal volume ventilation in mice

Mechanical ventilation is the major cause of iatrogenic lung damage in intensive care units. Although inflammation is known to be involved in ventilator-induced lung injury (VILI), several aspects of this process are still unknown. Pentraxin 3 (PTX3) is an acute phase protein with important regulatory functions in inflammation which has been found elevated in patients with acute respiratory distress syndrome. This study aimed at investigating the direct effect of PTX3 production in the pathogenesis of VILI. Genetically modified mice deficient and that over express murine Ptx3 gene were subjected to high tidal volume ventilation (V-T = 45 mL/kg, PEEPzero). Morphological changes and time required for 50% increase in respiratory system elastance were evaluated. Gene expression profile in the lungs was also investigated in earlier times in Ptx3-overexpressing mice. Ptx3 knockout and wild-type mice developed same lung injury degree in similar times (156 +/- 42 min and 148 +/- 41 min, respectively: p = 0.8173). However, Ptx3 overexpression led to a faster development of VILI in Ptx3-overexpressing mice (77 +/- 29 min vs 118 +/- 41 min, p = 0.0225) which also displayed a faster kinetics of Il1b expression and elevated Ptx3, Cxcl1 and Ccl2 transcripts levels in comparison with wild-type mice assessed by quantitative real-time polymerase chain reaction. Ptx3 deficiency did not impacted the time for VILI induced by high tidal volume ventilation but Ptx3-overexpression increased inflammatory response and reflected in a faster VILI development. (C) 2012 Elsevier Ltd. All rights reserved.

Practices of use of nasal intermittent positive pressure ventilation (NIPPV) in neonatology in northeastern Brazil

Objective: To investigate the use of nasal intermittent positive pressure ventilation (NIPPV) in level three neonatal intensive care units (NICU) in northeastern Brazil. Methods: This observational cross-sectional survey was conducted from March 2009 to January 2010 in all level three NICUs in northeastern Brazil that are registered in the Brazilian Registry of Health Establishments (Cadastro Nacional de Estabelecimentos de Saude, CNES) of the Ministry of Health. Questionnaires about the use of NIPPV were sent to the NICU directors in each institution. Statistical analysis was conducted using the software Epi-Info 6.04 and double data entry. A chi-square test was used to compare variables, and the level of statistical significance was set at p <= 0.05. Results: This study identified 93 level three NICUs in northeastern Brazil registered in CNES, and 87% answered the study questionnaire. Most classified themselves as private institutions (30.7%); 98.7% used NIPPV; 92.8 % adapted mechanical ventilators for NIPPV and used short binasal prongs as the interface (94.2%). Only 17.3% of the units had a protocol for the use of NIPPV. Mean positive inspiratory pressure and positive end-expiratory pressure were 20.0 cmH(2)O (standard deviation [SD]: 4.47) and 5.0 cmH(2)O (SD: 0.84). Conclusion: NICUs in northeastern Brazil use nasal intermittent positive pressure ventilation, but indications and ventilation settings are not the same in the different institutions.

Prognostic significance of the number of lymph nodes in elective neck dissection for tongue and mouth floor cancers

The presence of metastatic lymph nodes is a relevant aspect in the treatment of head and neck cancer, bringing about a 50% reduction in survival. Objective: To assess the number of lymph nodes removed in the neck dissection and their relationship with the prognosis. Methods: A retrospective study involving 143 patients with tongue and mouth floor epidermoid carcinoma, which histological exam showed no lymph node metastases. Among those, 119 were males and 24 females, with mean age of 54 years. As to the primary tumor site, 65 were in the tongue and 78 in the mouth floor. T stage distribution was of four T1, 84 T2, 36 T3 and 19 T4. We carried out 176 neck dissections, unilateral in 110 cases and bilateral in 33. Of these, 78 were radical and 98 selective. The patients were broken down into three groups, according to the 33 and 66 percentiles of the number of lymph nodes resected. Results: The mean number of resected lymph nodes was 27; 24 in selective dissections and 31 in the complete ones. We did not have statistically significant differences when associated to the T and N stages. Conclusions: The larger number of lymph nodes dissected in the neck dissection identifies the group of better prognoses among pN0 cases.

Electric Ventilation: indications for and technical aspects of diaphragm pacing stimulation surgical implantation

Objective: Patients with high cervical spinal cord injury are usually dependent on mechanical ventilation support, which, albeit life saving, is associated with complications and decreased life expectancy because of respiratory infections. Diaphragm pacing stimulation (DPS), sometimes referred to as electric ventilation, induces inhalation by stimulating the inspiratory muscles. Our objective was to highlight the indications for and some aspects of the surgical technique employed in the laparoscopic insertion of the DPS electrodes, as well as to describe five cases of tetraplegic patients submitted to the technique. Methods: Patient selection involved transcutaneous phrenic nerve studies in order to determine whether the phrenic nerves were preserved. The surgical approach was traditional laparoscopy, with four ports. The initial step was electrical mapping in order to locate the "motor points" (the points at which stimulation would cause maximal contraction of the diaphragm). If the diaphragm mapping was successful, four electrodes were implanted into the abdominal surface of the diaphragm, two on each side, to stimulate the branches of the phrenic nerve. Results: Of the five patients, three could breathe using DPS alone for more than 24 h, one could do so for more than 6 h, and one could not do so at all. Conclusions: Although a longer follow-up period is needed in order to reach definitive conclusions, the initial results have been promising. At this writing, most of our patients have been able to remain ventilator-free for long periods of time.

Single Center Experience With Elective Surgical Patients as Living Kidney Donors

Purpose. To report a single center experience with elective surgical patients as living kidney donors. Methods. We retrospectively analyzed a prospective database of 458 living kidney donors from September 2005 to May 2011. Fifteen (3.2%) of them were elective surgical patients simultaneously undergoing living donor nephrectomy. We reviewed age, gender, operative time, intraoperative blood transfusion, intra- and postoperative complications, as well as length of hospital stay. Recipients were evaluated for delayed graft function. Four hundred forty-three patients undergoing living donor nephrectomy alone composed the control group. Results. Among the elective surgical patients group, the mean (range) operative time was 155 (90 to 310) minutes and mean (range) length of hospital stay was 3 (2 to 9) days. One (6.7%) recipient displayed delayed graft function. Among the regular living kidney donors group, the mean (range) operative time was 100 (70 to 150) minutes, mean (range) length of hospital stay was 3 (2 to 5) days, and delayed graft function was observed in 5.6% of recipients. Only operative time (P = .03) was significantly different between the groups. Conclusions. Elective surgical patients are potential donors who may be treated at the same time as the living donor nephrectomy.

Low mechanical ventilation times and reintubation rates associated with a specific weaning protocol in an intensive care unit setting: a retrospective study

OBJECTIVES: A number of complications exist with invasive mechanical ventilation and with the use of and withdrawal from prolonged ventilator support. The use of protocols that enable the systematic identification of patients eligible for an interruption in mechanical ventilation can significantly reduce the number of complications. This study describes the application of a weaning protocol and its results. METHODS: Patients who required invasive mechanical ventilation for more than 24 hours were included and assessed daily to identify individuals who were ready to begin the weaning process. RESULTS: We studied 252 patients with a median mechanical ventilation time of 3.7 days (interquartile range of 1 to 23 days), a rapid shallow breathing index value of 48 (median), a maximum inspiratory pressure of 40 cmH2O, and a maximum expiratory pressure of 40 cm H2O (median). Of these 252 patients, 32 (12.7%) had to be reintubated, which represented weaning failure. Noninvasive ventilation was used postextubation in 170 (73%) patients, and 15% of these patients were reintubated, which also represented weaning failure. The mortality rate of the 252 patients studied was 8.73% (22), and there was no significant difference in the age, gender, mechanical ventilation time, and maximum inspiratory pressure between the survivors and nonsurvivors. CONCLUSIONS: The use of a specific weaning protocol resulted in a lower mechanical ventilation time and an acceptable reintubation rate. This protocol can be used as a comparative index in hospitals to improve the weaning system, its monitoring and the informative reporting of patient outcomes and may represent a future tool and source of quality markers for patient care.

N-acetylcysteine prevents pulmonary edema and acute kidney injury in rats with sepsis submitted to mechanical ventilation

Campos R, Shimizu MH, Volpini RA, de Bragan a AC, Andrade L, Lopes FD, Olivo C, Canale D, Seguro AC. N-acetylcysteine prevents pulmonary edema and acute kidney injury in rats with sepsis submitted to mechanical ventilation. Am J Physiol Lung Cell Mol Physiol 302: L640-L650, 2012. First published January 20, 2012; doi: 10.1152/ajplung.00097.2011.-Sepsis is a common cause of acute kidney injury (AKI) and acute lung injury. Oxidative stress plays as important role in such injury. The aim of this study was to evaluate the effects that the potent antioxidant N-acetylcysteine (NAC) has on renal and pulmonary function in rats with sepsis. Rats, treated or not with NAC (4.8 g/l in drinking water), underwent cecal ligation and puncture (CLP) 2 days after the initiation of NAC treatment, which was maintained throughout the study. At 24 h post-CLP, renal and pulmonary function were studied in four groups: control, control + NAC, CLP, and CLP + NAC. All animals were submitted to low-tidal-volume mechanical ventilation. We evaluated respiratory mechanics, the sodium cotransporters Na-K-2Cl (NKCC1) and the alpha-subunit of the epithelial sodium channel (alpha-ENaC), polymorphonuclear neutrophils, the edema index, oxidative stress (plasma thiobarbituric acid reactive substances and lung tissue 8-isoprostane), and glomerular filtration rate. The CLP rats developed AKI, which was ameliorated in the CLP + NAC rats. Sepsis-induced alterations in respiratory mechanics were also ameliorated by NAC. Edema indexes were lower in the CLP + NAC group, as was the wet-to-dry lung weight ratio. In CLP + NAC rats, alpha-ENaC expression was upregulated, whereas that of NKCC1 was downregulated, although the difference was not significant. In the CLP + NAC group, oxidative stress was significantly lower and survival rates were significantly higher than in the CLP group. The protective effects of NAC (against kidney and lung injury) are likely attributable to the decrease in oxidative stress, suggesting that NAC can be useful in the treatment of sepsis.

Comparison of 3 modes of automated weaning from mechanical ventilation: A bench study

Purpose: Automated weaning modes are available in some mechanical ventilators, but no studies compared them hitherto. We compared the performance of 3 automated modes under standard and challenging situations. Methods: We used a lung simulator to compare 3 automated modes, adaptive support ventilation (ASV), mandatory rate ventilation (MRV), and Smartcare, in 6 situations, weaning success, weaning failure, weaning success with extreme anxiety, weaning success with Cheyne-Stokes, weaning success with irregular breathing, and weaning failure with ineffective efforts. Results: The 3 modes correctly recognized the situations of weaning success and failure, even when anxiety or irregular breathing were present but incorrectly recognized weaning success with Cheyne-Stokes. MRV incorrectly recognized weaning failure with ineffective efforts. Time to pressure support (PS) stabilization was shorter for ASV (1-2 minutes for all situations) and MRV (1-7 minutes) than for Smartcare (8-78 minutes). ASV had higher rates of PS oscillations per 5 minutes (4-15), compared with Smartcare (0-1) and MRV (0-12), except when extreme anxiety was present. Conclusions: Smartcare, ASV, and MRV were equally able to recognize weaning success and failure, despite the presence of anxiety or irregular breathing but performed incorrectly in the presence of Cheyne-Stokes. PS behavior over the time differs among modes, with ASV showing larger and more frequent PS oscillations over the time. Clinical studies are needed to confirm our results. (C) 2012 Elsevier Inc. All rights reserved.