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    Inhibition of phagocytosis and killing of bacteria by anaesthetic agents in vitro. Krumholz W,Endrass J,Hempelmann G British journal of anaesthesia Polymorphonuclear leucocytes (PMNL) are an essential contribution to protection from bacterial infection. We have examined the effects of thiopentone, etomidate, ketamine and flunitrazepam on phagocytosis and killing of Staphylococcus aureus and Escherichia coli by PMNL in vitro with fluorescence microscopy. All anaesthetic agents significantly inhibited both phagocytosis and bactericidal activity. The additives in the commercial preparations may have contributed to the suppression. 10.1093/bja/75.1.66
    Microbial growth in propofol formulations with disodium edetate and the influence of venous access system dead space. Fukada T,Ozaki M Anaesthesia Propofol formulated in lipid supports microbial growth. We hypothesised that propofol with disodium edetate would suppress microbial growth more than propofol without disodium edetate. We examined bacterial growth in vitro and bacterial survival in the dead space of different venous access systems. Bacteria in propofol with disodium edetate (Diprivan; AstraZeneca, London, UK) and without disodium edetate (1% Propofol inj. 'Maruishi'; Maruishi Pharmaceutical Co. Ltd, Osaka, Japan) survived and grew in the dead space of the venous access systems, although propofol with disodium edetate suppressed bacterial growth more than propofol without. Disodium edetate is effective in retarding microbial growth. However, for prevention of healthcare-associated infections, medical professionals should maintain strict aseptic precautions when handling propofol, use disodium edetate-containing formulations, and should consider using venous access systems without dead space. 10.1111/j.1365-2044.2007.05002.x
    A comparison of microbial growth in alfaxalone, propofol and thiopental. Strachan F A,Mansel J C,Clutton R E The Journal of small animal practice OBJECTIVES:To compare the growth of Staphylococcus aureus and Escherichia coli in alfaxalone with that in propofol and thiopental and to evaluate contaminant microbial growth in these agents under two different conditions of storage and handling. METHODS:Known quanta of S aureus and E coli were inoculated into separate 5 ml samples of propofol, thiopental and alfaxalone. Quantitative bacterial analysis was performed at intervals over a 14 day period. Commercial preparations of propofol, thiopental and alfaxalone were stored and handled using "dirty" or "clean" techniques. Microbial quantification and identification was performed over a 14 day period. RESULTS:S aureus and E coli grew rapidly in propofol after six hours. Both bacteria were killed by thiopental. S aureus numbers slowly declined in alfaxalone; E coli growth was rapid after 24 hours. In "dirty" and "clean" groups of intravenous anaesthetics, 9.3 and 7.4 per cent of samples, respectively, were positive for microbial growth; none were considered to represent colonisation of bottles. CLINICAL SIGNIFICANCE:Alfaxalone supports growth of some microorganisms but less readily than propofol. Bacterial colonisation of intravenous anaesthetic bottles is uncommon, but contamination as syringes are prepared for injection occurs regardless of storage and handling technique. 10.1111/j.1748-5827.2007.00473.x
    Inhibition of bacterial growth by different mixtures of propofol and thiopentone. Joubert K E,Picard J,Sethusa M Journal of the South African Veterinary Association Propofol is, as a result of its formulation, an ideal bacterial and yeast culture medium. An outbreak of sepsis in humans and an increase in wound infections in dogs has been ascribed to the use of propofol. It has been previously reported that a 1:1 mixture of propofol and thiopentone has bactericidal properties. This study was undertaken to determine if further serial mixtures of propofol and thiopentone maintained the bactericidal properties. Mixtures of 1:1 (solution A), 5:1 (solution B), 10:1 (solution C), 50:1 (solution D) and 100:1 (solution E) of 1% propofol to 2.5 % thiopentone, 2.5% thiopentone (solution T), 1% propofol (solution P) and saline (solution S) were prepared and inoculated with between 10(5) and 10(6) colony-forming units of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans. A sample was withdrawn from each solution at 0, 1, 6, 12, 48 and 120 hours after inoculation and a bacterial count was performed. This study showed that thiopentone and solution A behaved in similar fashion by inhibiting bacterial growth and was bactericidal after 48 hours. Solution B was not bactericidal against S. aureus and C. albicans. Propofol and solutions D and E all supported growth of all the organisms tested. These data indicate that mixtures of propofol and thiopentone at a ratio less than 1:1 do not maintain the bactericidal properties. 10.4102/jsava.v76i2.403
    Survival of Staphylococcus epidermidis in Propofol and Intralipid in the Dead Space of Intravenous Injection Ports. Noble Ronan M N,Salim Saad Y,Walker Bradley,Khadaroo Rachel G,Chiarella Angelo B,Gragasin Ferrante S,Bourque Stephane L Anesthesia and analgesia We tested whether propofol or Intralipid inoculated with Staphylococcus epidermidis would promote bacterial growth within an intravenous (IV) injection hub, a site prone to bacterial contamination. In tubes incubated under optimal conditions, S epidermidis exhibited growth in Intralipid, but not in propofol. In contrast, within the IV hub incubated with either propofol or intralipid at room temperature, S epidermidis bacterial numbers declined with time, and virtually no contamination remained after 12 hours. These data suggest that certain IV lines are inhospitable for S epidermidis. 10.1213/ANE.0000000000002654
    The preventive effect of diphenhydramine on bacterial growth in propofol: a laboratory study. Güzelant A,Apiliogullari S,Kara I,Turhan V,Apiliogullari B,Yilmaz H,Balasar M,Duman A European journal of anaesthesiology BACKGROUND AND OBJECTIVE:Diphenhydramine has local anaesthetic and antimicrobial activity and may be used to prevent intravenous propofol injection pain. We studied the effect of adding diphenhydramine to propofol emulsions for preventing bacterial growth. METHODS:Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Candida albicans cultures were inoculated into the following solutions: 1% propofol, 0.05% diphenhydramine + 1% propofol, 0.1% diphenhydramine + 1% propofol, 0.2% diphenhydramine + 1% propofol, 0.3% diphenhydramine + 1% propofol, 1% diphenhydramine and 0.1% lidocaine + 1% propofol. A 100-microL of inoculum suspension adjusted for each of the micro-organisms was added separately to each tube and left at 20 degrees C. A 10-microL aliquot of each mixture was inoculated onto blood agar medium at 5 and 24 h. These plates were incubated at 35 degrees C for 24 h. Each plated medium was read, and the number of colony-forming units were counted and recorded (n = 2). Analysis of variance (ANOVA) with a post hoc Tukey HSD test and paired t-tests were used for data analysis. P < 0.05 was considered as significant. RESULTS:Diphenhydramine inhibited bacterial growth in propofol solutions in a dose-dependent manner. It was more effective than 0.1% lidocaine at similar concentrations in preventing bacterial growth for all organisms. CONCLUSION:Diphenhydramine had a significant inhibitory effect on bacterial growth in propofol. 10.1017/S0265021508004377
    Effect of transforming growth factor-beta neutralization on survival and bacterial clearance in a murine model of Pseudomonas aeruginosa burn wound infection. Huang Zhiyu,Pereira Clifford,Toliver-Kinsky Tracy,Murphey Erle D,Varma Tushar K,Lin Cheng Y,Herndon David N,Sherwood Edward R Journal of burn care & research : official publication of the American Burn Association Transforming growth factor-beta (TGF-beta), a cytokine with anti-inflammatory properties, may contribute to postburn immunosuppression. This study was designed to determine whether neutralizing TGF-beta in burned mice could improve resistance to infection. C57BL/6J mice received a 35% TBSA flame burn under isoflurane anesthesia. Four days after injury, mice were treated with TGF-beta antibody or nonspecific IgG. On day 5 after burn injury, mice were inoculated with Pseudomonas aeruginosa at the burn wound site or received intraperitoneal injection with P. aeruginosa. Mice treated with anti-TGF-beta exhibited significantly improved survival compared with mice treated with nonspecific IgG after challenge with P. aeruginosa at the burn wound site or after intraperitoneal injection of P. aeruginosa. In mice with burn wound infections, bacterial counts in burn wounds, blood, and lung were decreased in mice treated with anti-TGF-beta compared with mice treated with control IgG. Bacterial counts in lung and blood after intraperitoneal challenge with P. aeruginosa also were significantly lower in burned mice treated with anti-TGF-beta compared with those treated with nonspecific IgG. Our data suggest that neutralization of TGF-beta at 4 days after burn injury in mice improves local and systemic clearance of P. aeruginosa and enhances survival after P. aeruginosa challenge. 10.1097/01.BCR.0000238083.95170.2A
    The effect of ketamine anesthesia on the immune function of mice with postoperative septicemia. Takahashi Tetsuya,Kinoshita Manabu,Shono Satoshi,Habu Yoshiko,Ogura Takahiro,Seki Shuhji,Kazama Tomiei Anesthesia and analgesia BACKGROUND:It is unknown how ketamine anesthesia immunologically affects the outcome of patients with postoperative septicemia. We investigated the effects of ketamine anesthesia on mice with an Escherichia coli or lipopolysaccharide (LPS) challenge after laparotomy, focusing on phagocytosis by liver macrophages (Kupffer cells) and cytokine production. METHODS:C57BL/6 mice received ketamine or sevoflurane anesthesia during laparotomy, which was followed by an E. coli or LPS challenge; thereafter, mouse survival rates and cytokine secretions were examined. The effects of a β-adrenoceptor antagonist, nadolol, on ketamine anesthesia were also assessed to clarify the mechanisms of ketamine-induced immunosuppressive effects. RESULTS:Ketamine anesthesia increased the mouse survival rate after LPS challenge after laparotomy compared with sevoflurane anesthesia, whereas such an effect of ketamine was not observed after E. coli challenge. Ketamine suppressed tumor necrosis factor (TNF) and interferon (IFN)-γ secretion after LPS and E. coli challenge. When bacterial growth was inhibited using an antibiotic, ketamine anesthesia effectively improved mouse survival after E. coli challenge compared with sevoflurane anesthesia. Neutralization of TNF also improved survival and decreased IFN-γ secretion after bacterial challenge in antibiotic-treated mice with sevoflurane anesthesia, suggesting that ketamine's suppression of TNF may improve survival. Ketamine also suppressed in vivo phagocytosis of microspheres by Kupffer cells in LPS-challenged mice. Concomitant use of nadolol with an anesthetic dose of ketamine did not restore TNF suppression in LPS-challenged mice, suggesting a mechanism independent of the β-adrenergic pathway. However, it restored TNF secretion under low-dose ketamine (10% anesthetic dose). In contrast, nadolol restored the decrease in phagocytosis by Kupffer cells, which was induced by the anesthetic dose of ketamine via the β-adrenergic pathway, suggesting distinct mechanisms. CONCLUSION:Ketamine suppresses TNF production and phagocytosis by Kupffer cells/macrophages. Therefore, unless bacterial growth is well controlled (by an antibiotic), postoperative infection might not improve despite reduction of the inflammatory response. 10.1213/ANE.0b013e3181ed12fc
    Mechanical Ventilation Alters the Development of Staphylococcus aureus Pneumonia in Rabbit. Barbar Saber-Davide,Pauchard Laure-Anne,Bruyère Rémi,Bruillard Caroline,Hayez Davy,Croisier Delphine,Pugin Jérôme,Charles Pierre-Emmanuel PloS one Ventilator-associated pneumonia (VAP) is common during mechanical ventilation (MV). Beside obvious deleterious effects on muco-ciliary clearance, MV could adversely shift the host immune response towards a pro-inflammatory pattern through toll-like receptor (TLRs) up-regulation. We tested this hypothesis in a rabbit model of Staphylococcus aureus VAP. Pneumonia was caused by airway challenge with S. aureus, in either spontaneously breathing (SB) or MV rabbits (n = 13 and 17, respectively). Pneumonia assessment regarding pulmonary and systemic bacterial burden, as well as inflammatory response was done 8 and 24 hours after S. aureus challenge. In addition, ex vivo stimulations of whole blood taken from SB or MV rabbits (n = 7 and 5, respectively) with TLR2 agonist or heat-killed S. aureus were performed. Data were expressed as mean±standard deviation. After 8 hours of infection, lung injury was more severe in MV animals (1.40±0.33 versus [vs] 2.40±0.55, p = 0.007), along with greater bacterial concentrations (6.13±0.63 vs. 4.96±1.31 colony forming units/gram, p = 0.002). Interleukin (IL)-8 and tumor necrosis factor (TNF)-αserum concentrations reached higher levels in MV animals (p = 0.010). Whole blood obtained from MV animals released larger amounts of cytokines if stimulated with TLR2 agonist or heat-killed S. aureus (e.g., TNF-α: 1656±166 vs. 1005±89; p = 0.014). Moreover, MV induced TLR2 overexpression in both lung and spleen tissue. MV hastened tissue injury, impaired lung bacterial clearance, and promoted a systemic inflammatory response, maybe through TLR2 overexpression. 10.1371/journal.pone.0158799
    Bacteriostatic effect of mixtures of 1% propofol with 4% lidocaine versus 4% lidocaine alone: regards on microbiologic studies in the field of anesthesiology. Zorrilla-Vaca Andrés,Escandón-Vargas Kevin Infection control and hospital epidemiology 10.1086/676441
    Impact of Anesthesia Protocols on In Vivo Bioluminescent Bacteria Imaging Results. Chuzel Thomas,Sanchez Violette,Vandamme Marc,Martin Stéphane,Flety Odile,Pager Aurélie,Chabanel Christophe,Magnier Luc,Foskolos Marie,Petit Océane,Rokbi Bachra,Chereul Emmanuel PloS one Infectious murine models greatly benefit from optical imaging using bioluminescent bacteria to non-invasively and repeatedly follow in vivo bacterial infection. In this context, one of the most critical parameters is the bioluminescence sensitivity to reliably detect the smallest number of bacteria. Another critical point is the anesthetic approaches that have been demonstrated to impact the bioluminescence flux emission in studies with luciferase-transfected tumor cells. However, this impact has never been assessed on bacteria bioluminescent models. To this end, we investigated the effects of four anesthesia protocols on the bioluminescence flux in a central venous catheter murine model (SKH1-hr(hr) mice) infected by a bioluminescent S. aureus Xen36 strain. Bioluminescence imaging was performed on mice anesthetized by either ketamine/xylazine (with or without oxygen supplementation), or isoflurane carried with air or oxygen. Total flux emission was determined in vivo daily for 3 days and ex vivo at the end of the study together with a CFU counting of the biofilm in the catheter. Bioluminescence flux differences appear between the different anesthetic protocols. Using a ketamine/xylazine anesthesia (with air), bacteria detection was impossible since the bioluminescence signal remains in the background signal. Mice anesthetized with isoflurane and oxygen led to a signal significantly higher to the background all along the kinetics. The use of isoflurane in air presents a bioluminescence signal similar to the use of ketamine/xylazine with oxygen. These data highlight the importance of oxygen to improve bioluminescence flux by bacteria with isoflurane as well as with ketamine/xylazine anesthetics. As a conclusion, we recommend the use of isoflurane anesthetic with oxygen to increase the bioluminescence sensitivity in this kind of study. 10.1371/journal.pone.0134048
    Anesthesia in patients with infectious disease caused by multi-drug resistant bacteria. Einav Sharon,Wiener-Well Yonit Current opinion in anaesthesiology PURPOSE OF REVIEW:Up to 50% of specific bacterial strains in healthcare admission facilities are multi-drug resistant organisms (MDROs). Involvement of anesthesiologists in management of patients carrying/at risk of carrying MDROs may decrease transmission in the Operating Room (OR). RECENT FINDINGS:Anesthesiologists, their work area and tools have all been implicated in MDRO outbreaks. Causes include contamination of external ventilation circuits and noncontribution of filters to prevention, inappropriate decontamination procedures for nondisposable equipment (e.g. laryngoscopes, bronchoscopes and stethoscopes) and the anesthesia workplace (e.g. external surfaces of cart and anesthesia machine, telephones and computer keyboards) during OR cleaning and lack of training in sterile drug management. SUMMARY:Discussions regarding the management of potential MDRO carriers must include anesthesia providers to optimize infection control interventions as well as the anesthesia method, the location of surgery and recovery and the details of patient transport. Anesthesia staff must learn to identify patients at risk for MDRO infection. Antibiotic prophylaxis, although not evidence based, should adhere to known best practices. Adjuvant therapies (e.g. intranasal Mupirocin and bathing with antiseptics) should be considered. Addition of nonmanual OR cleaning methods such as ultraviolet irradiation or gaseous decontamination is encouraged. Anesthesiologists must undergo formal training in sterile drug preparation and administration. 10.1097/ACO.0000000000000457
    General Anesthesia Alters the Diversity and Composition of the Intestinal Microbiota in Mice. Serbanescu Mara A,Mathena Reilley P,Xu Jing,Santiago-Rodriguez Tasha,Hartsell Theresa L,Cano Raul J,Mintz Cyrus D Anesthesia and analgesia Dysbiosis of the intestinal microbiota has been shown to result in altered immune responses and increased susceptibility to infection; as such, the state of the intestinal microbiome may have profound implications in the perioperative setting. In this first-in-class study, we used 16s ribosomal RNA sequencing and analysis in a mouse model of general anesthesia to investigate the effects of volatile anesthetics on the diversity and composition of the intestinal microbiome. After 4-hour exposure to isoflurane, we observed a decrease in bacterial diversity. Taxonomic alterations included depletion of several commensal bacteria including Clostridiales. These data identify volatile anesthetics as potential contributors to microbial dysbiosis in the postoperative patient. 10.1213/ANE.0000000000003938
    Biofilm inhibiting activity of betacyanins from red pitahaya (Hylocereus polyrhizus) and red spinach (Amaranthus dubius) against Staphylococcus aureus and Pseudomonas aeruginosa biofilms. Yong Y Y,Dykes G,Lee S M,Choo W S Journal of applied microbiology AIMS:To investigate the biofilm inhibitory activity of betacyanins from red pitahaya (Hylocereus polyrhizus) and red spinach (Amaranthus dubius) against Staphylococcus aureus and Pseudomonas aeruginosa biofilms. METHODS AND RESULTS:The pulp of red pitahaya and the leaves of red spinach were extracted using methanol followed by subfractionation to obtain betacyanin fraction. The anti-biofilm activity was examined using broth microdilution assay on polystyrene surfaces and expressed as minimum biofilm inhibitory concentration (MBIC). The betacyanin fraction from red spinach showed better anti-biofilm activity (MBIC: 0·313-1·25 mg ml ) against five Staph. aureus strains while the betacyanin fraction from red pitahaya showed better anti-biofilm activity (MBIC: 0·313-0·625 mg ml ) against four P. aeruginosa strains. Both betacyanin fraction significantly reduced hydrophobicity of Staph. aureus and P. aeruginosa strains. Numbers of Staph. aureus and P. aeruginosa attached to polystyrene were also reduced without affecting their cell viability. CONCLUSION:Betacyanins can act as anti-biofilm agents against the initial step of biofilm formation, particularly on a hydrophobic surface like polystyrene. SIGNIFICANCE AND IMPACT OF THE STUDY:This study is the first to investigate the use of betacyanin as a biofilm inhibitory agent. Betacyanin could potentially be used to reduce the risk of biofilm-associated infections. 10.1111/jam.14091
    Differential protection against oxidative stress and nitric oxide overproduction in cardiovascular and pulmonary systems by propofol during endotoxemia. Liu Yen-Chin,Chang Alice Y W,Tsai Yu-Chuan,Chan Julie Y H Journal of biomedical science BACKGROUND:Both overproduction of nitric oxide (NO) and oxidative injury of cardiovascular and pulmonary systems contribute to fatal cardiovascular depression during endotoxemia. We investigated in the present study the relative contribution of oxidative stress and NO to cardiovascular depression during different stages of endotoxemia, and delineated their roles in cardiovascular protective effects of a commonly used anesthetic propofol during endotoxemia. METHODS:Experimental endotoxemia was induced by systemic injection of E. coli lipopolysaccharide (LPS, 15 mg/kg) to Sprague-Dawley rats that were maintained under propofol (15 or 30 mg/kg/h, i.v.) anesthesia. Mean systemic arterial pressure (MSAP) and heart rate (HR) were monitored for 6 h after the endotoxin. Tissue level of NO was measured by chemical reduction-linked chemiluminescence and oxidative burst activity was determined using dihydroethidium method. Expression of NO synthase (NOS) was determined by immunoblotting. The Scheffé multiple range test was used for post hoc statistical analysis. RESULTS:Systemic injection of LPS (15 mg/kg) induced biphasic decreases in MSAP and HR. In the heart, lung and aorta, an abrupt increase in lipid peroxidation, our experimental index of oxidative tissue injury, was detected in early stage and sustained during late stage cardiovascular depression. LPS injection, on the other hand, induced a gradual increase in tissue nitrite and nitrate levels in the same organs that peaked during late stage endotoxemia. Propofol infusion (15 or 30 mg/kg/h, i.v.) significantly attenuated lipid peroxidation in the heart, lung and aorta during early and late stage endotoxemia. High dose (30 mg/kg/h, i.v.) propofol also reversed the LPS-induced inducible NO synthase (iNOS) upregulation and NO production in the aorta, alongside a significant amelioration of late stage cardiovascular depression and increase in survival time during endotoxemia. CONCLUSION:Together these results suggest that oxidative injury and NO may play a differential role in LPS-induced cardiovascular depression. Oxidative tissue injury is associated with both early and late stage; whereas NO is engaged primarily in late stage cardiovascular depression. Moreover, propofol anesthesia may protect against fatal cardiovascular depression during endotoxemia by attenuating the late stage NO surge in the aorta, possibly via inhibition of iNOS upregulation by the endotoxin. 10.1186/1423-0127-16-8
    Propofol inhibits lipopolysaccharide-induced tumor necrosis factor-alpha expression and myocardial depression through decreasing the generation of superoxide anion in cardiomyocytes. Tang Jing,Hu Ji-Jie,Lu Chun-Hua,Liang Jia-Ni,Xiao Jin-Fang,Liu You-Tan,Lin Chun-Shui,Qin Zai-Sheng Oxidative medicine and cellular longevity TNF-α has been shown to be a major factor responsible for myocardial depression in sepsis. The aim of this study was to investigate the effect of an anesthetic, propofol, on TNF-α expression in cardiomyocytes treated with LPS both in vivo and in vitro. In cultured cardiomyocytes, compared with control group, propofol significantly reduced protein expression of gp91phox and phosphorylation of extracellular regulated protein kinases 1/2 (ERK1/2) and p38 MAPK, which associates with reduced TNF-α production. In in vivo mice studies, propofol significantly improved myocardial depression and increased survival rate of mice after LPS treatment or during endotoxemia, which associates with reduced myocardial TNF-α production, gp91phox, ERK1/2, and p38 MAPK. It is concluded that propofol abrogates LPS-induced TNF-α production and alleviates cardiac depression through gp91phox/ERK1/2 or p38 MAPK signal pathway. These findings have great clinical importance in the application of propofol for patients enduring sepsis. 10.1155/2014/157376
    Propofol increases morbidity and mortality in a rat model of sepsis. Schläpfer Martin,Piegeler Tobias,Dull Randal O,Schwartz David E,Mao Mao,Bonini Marcelo G,Z'Graggen Birgit Roth,Beck-Schimmer Beatrice,Minshall Richard D Critical care (London, England) INTRODUCTION:Severe sepsis is associated with approximately 50% mortality and accounts for tremendous healthcare costs. Most patients require ventilatory support and propofol is commonly used to sedate mechanically ventilated patients. Volatile anesthetics have been shown to attenuate inflammation in a variety of different settings. We therefore hypothesized that volatile anesthetic agents may offer beneficial immunomodulatory effects during the course of long-term intra-abdominal sepsis in rats under continuous sedation and ventilation for up to 24 hours. METHODS:Sham operation or cecal ligation and puncture (CLP) was performed in adult male Wistar rats followed by mechanical ventilation. Animals were sedated for 24 hours with propofol (7 to 20 mg/kg/h), sevoflurane, desflurane or isoflurane (0.7 minimal alveolar concentration each). RESULTS:Septic animals sedated with propofol showed a mean survival time of 12 hours, whereas >56% of all animals in the volatile groups survived 24 hours (P <0.001). After 18 hours, base excess in propofol + CLP animals (-20.6 ± 2.0) was lower than in the volatile groups (isoflurane + CLP: -11.7 ± 4.2, sevoflurane + CLP: -11.8 ± 3.5, desflurane + CLP -14.2 ± 3.7; all P <0.03). Plasma endotoxin levels reached 2-fold higher levels in propofol + CLP compared to isoflurane + CLP animals at 12 hours (P <0.001). Also blood levels of inflammatory mediators (tumor necrosis factor-α, interleukin-1β, interleukin-10, CXCL-2, interferon-γ and high mobility group protein-1) were accentuated in propofol + CLP rats compared to the isoflurane + CLP group at the same time point (P <0.04). CONCLUSIONS:This is the first study to assess prolonged effects of sepsis and long-term application of volatile sedatives compared to propofol on survival, cardiovascular, inflammatory and end organ parameters. Results indicate that volatile anesthetics dramatically improved survival and attenuate systemic inflammation as compared to propofol. The main mechanism responsible for adverse propofol effects could be an enhanced plasma endotoxin concentration, leading to profound hypotension, which was unresponsive to fluid resuscitation. 10.1186/s13054-015-0751-x
    Propofol increases preload dependency in septic shock patients. Yu Tao,Peng Xiao,Liu Ling,Li Qing,Huang Yingzi,Guo Fengmei,Yang Yi,Qiu Haibo The Journal of surgical research BACKGROUND:Predicting fluid responsiveness is crucial for fluid administration in septic shock patients. Midazolam and propofol decrease vascular tone and venous return, which may influence preload dependency. However, little is known about the effects of these two sedatives on preload dependency in septic shock patients. We evaluated the effects of sedation with propofol or midazolam on preload dependency in septic shock patients who have been fluid resuscitated. METHODS:Forty-three septic shock patients who were undergoing early goal-directed therapy resuscitated within 24 h were enrolled. The patients were randomly divided into the midazolam group and the propofol group. An initial passive leg-raising test (PLR1) was performed to evaluate passive leg raising test (PLR) responsiveness. Then, the patients were infused with midazolam or propofol. After increasing the doses of the sedatives to titrate to a Ramsay 4 score, a second passive leg raising test (PLR2) was conducted to evaluate PLR responsiveness. The primary end-point was the preload dependency before and after sedation with midazolam or propofol. RESULTS:In the midazolam-PLR1-negative patients, there was no difference between the changes in the cardiac index induced by PLR1 (PLR1-Δ cardiac function index [CI]) and the changes in the cardiac index induced by PLR2 (PLR2-Δ CI) (+1.4% ± 7.4% versus +1.7% ± 6.4%, P > 0.05). However, in the propofol-PLR1-negative patients, there was a significant increase in the PLR-Δ CI after sedation to a Ramsay 4 score compared with a Ramsay 3 score (+7.3% ± 4.8% versus +3.2% ± 4.7%, P = 0.008). There were no differences between PLR1-Δ CI and PLR2-Δ CI within the midazolam-PLR1-positive patients or within the propofol-PLR1-positive patients. CONCLUSIONS:In titrating the sedation level from a Ramsay 3 score to a Ramsay 4 score, propofol but not midazolam increased preload dependency in septic shock patients with fluid nonresponsiveness. 10.1016/j.jss.2014.08.050
    Propofol as a Risk Factor for ICU-Acquired Weakness in Septic Patients with Acute Respiratory Failure. Abdelmalik Peter A,Rakocevic Goran The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques BACKGROUND:Critical illness polyneuropathy (CIN) and critical illness myopathy (CIM), together "ICU-Acquired weakness (ICUAW)," occur frequently in septic patients. One of the proposed mechanisms for ICUAW includes prolonged inactivation of sodium channels. Propofol, used commonly in patients with acute respiratory failure (ARF), primarily acts via enhancement of GABAergic transmission but may also increase sodium channel inactivation, suggesting a potential interaction. METHODS:Electronic medical records and EMG reports of patients with ICUAW and a diagnosis of either sepsis, septicaemia, severe sepsis, or septic shock, concurrent with a diagnosis of acute respiratory failure (ARF), were retrospectively analyzed in a single center university hospital. RESULTS:74 cases were identified (50.0% men, age 58±14 years), and compared to age- and sex-matched controls. Of these, 51 (69%) had CIN, 19 (26%) had CIM, and 4 (5%) had both. Propofol exposure was significantly higher in patients with ICUAW compared to controls (63.5% vs. 33.8%, p<0.001). The odds ratio of developing ICUAW with propofol exposure was 3.4 (95% CI:1.7-6.7, p<0.001). Patients with ICUAW had significantly more days in hospital (59±44 vs. 30±23) and ICU (38±26 vs. 17±13), days dependent on mechanical ventilation (27±21 vs. 13±16), and rates of tracheostomy (79.7% vs. 36.5%) and gastrostomy (75.7% vs. 25.7%) (all p<0.001). They also received a significantly higher number of distinct intravenous antibiotics, cumulative days of antibiotic therapy, and exposure to vasopressors and paralytics. CONCLUSIONS:Propofol exposure may increase the risk of ICUAW in septic patients. An interaction through sodium channel inactivation is hypothesized. 10.1017/cjn.2016.424
    Outbreak of severe sepsis due to contaminated propofol: lessons to learn. Muller A E,Huisman I,Roos P J,Rietveld A P,Klein J,Harbers J B M,Dorresteijn J J,van Steenbergen J E,Vos M C The Journal of hospital infection Nosocomial infections are a frequent concern in healthcare. Despite the available knowledge on nosocomial infections and preventive measures, outbreaks of infections continue to occur. An outbreak of severe sepsis in patients who underwent minor procedures in an operating theatre during two consecutive days is described and analysed in this study. We performed a retrospective cohort study using epidemiological data in order to investigate the source of infection together with microbiological and on-site investigations and interviews. Seven patients met the case definition of postoperative systemic inflammatory response syndrome (SIRS). All other patients operated on over the same period served as controls. Of the risk factors investigated, general anaesthesia and propofol were statistically significant (P=0.003). Klebsiella pneumoniae and Serratia marcescens were cultured from opened vials of propofol, propofol-related devices and from blood cultures from two of the patients. These strains were genotypically indistinguishable. Lapses in aseptic preparation, handling and storage of the propofol were observed, and were the most probable cause of the extrinsic contamination. The daily procedure of handling propofol was not performed according to the manufacturer's recommendations, the main departure being the use of a single-use vial for multiple patients. This study documents the risk of infection due to contaminated propofol and the importance of having written guidelines for its handling. 10.1016/j.jhin.2010.06.003
    Effect of anaesthesia maintained with sevoflurane and propofol on surgical site infection after elective open gastrointestinal surgery. Shimizu K,Hirose M,Mikami S,Takamura K,Goi T,Yamaguchi A,Morioka K,Ichikawa T,Shigemi K The Journal of hospital infection Perioperative increase in oxidative activity in surgical patients reportedly prevents postoperative surgical site infection (SSI). Several clinical studies have shown that oxidative activity under sevoflurane anaesthesia was higher than that under propofol anaesthesia. Therefore, we hypothesised that sevoflurane anaesthesia would discourage SSI compared with propofol anaesthesia. To examine the effect of anaesthesia maintained with sevoflurane and propofol on SSI, a total of 265 consecutive adult patients, with American Society of Anesthesiologists physical status 1-3, who underwent elective open gastrointestinal surgery under general anaesthesia, were surveyed for SSI between January 2007 and December 2008. Sevoflurane or propofol was selected to maintain anaesthesia in 95 and 170 patients, respectively. A propensity score was used for pairwise matching of these patients to avoid selection biases between the two methods of anaesthesia. Propensity matching yielded 84 pairs of patients. We compared standardised infection ratios (SIRs), i.e. the quotient of the number of SSI cases observed and the number of SSI cases expected, calculated using data from the National Nosocomial Infection Surveillance, between sevoflurane and propofol anaesthesia. After propensity matching, SIR after sevoflurane anaesthesia was 1.89 [95% confidence interval (CI): 1.46-2.32], which was significantly lower than after propofol anaesthesia (4.78; 95% CI: 4.30-5.27) (P=0.02). This study suggests that sevoflurane tends to suppress SSI after elective open gastrointestinal surgery compared with propofol. 10.1016/j.jhin.2009.10.011
    Effect of Equipotent Doses of Propofol versus Sevoflurane Anesthesia on Regulatory T Cells after Breast Cancer Surgery. Oh Chung-Sik,Lee Jaemoon,Yoon Tae-Gyoon,Seo Eun-Hye,Park Hyun-Jun,Piao Liyun,Lee Seung-Hyun,Kim Seong-Hyop Anesthesiology WHAT WE ALREADY KNOW ABOUT THIS TOPIC:WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Clusters of differentiation 39 and 73, enzymes expressed on the surface of regulatory T cells, promote cancer recurrence and metastasis by suppressing immune cells. The authors hypothesized that propofol is less immunosuppressive than volatile anesthetics. The objective of this randomized trial was to compare the changes in cluster of differentiation 39 and 73 expression on regulatory T cells between propofol- and sevoflurane-based anesthesia during breast cancer surgery. METHODS:A total of 201 patients having breast cancer surgery were randomly assigned and analyzed (n = 99 for propofol, n = 102 for sevoflurane). Blood samples were obtained immediately before anesthesia induction and 1 and 24 h postoperatively. The frequency of cluster of differentiation 39 and 73 expression on circulating regulatory T cells (primary outcome) and the frequency of circulating type 1 and type 17 helper T cells, natural killer cells, and cytotoxic T cells were investigated. Serum cytokines and the neutrophil-to-lymphocyte ratio were also evaluated. RESULTS:Changes in cluster of differentiation 39 and 73 expression on regulatory T cells over time did not differ with propofol and sevoflurane groups (difference [95% confidence interval]: 0.01 [-2.04 to 2.06], P = 0.995 for cluster of differentiation 39; -0.93 [-3.12 to 1.26], P = 0.403 for cluster of differentiation 73). There were no intergroup differences in type 1, type 17 helper T cells, natural killer cells, cytotoxic T cells, cytokines, or the neutrophil-to-lymphocyte ratio. CONCLUSIONS:Changes in immune cells were similar with propofol and sevoflurane during breast cancer surgery. The effect of anesthetics on the perioperative immune activity may be minimal during cancer surgery. 10.1097/ALN.0000000000002382
    Effects of propofol on vasopressor use in patients with sepsis and severe sepsis: A pilot study. Marler Jacob,Mohrien Kerry,Kimmons Lauren A,Vandigo Joseph E,Oliphant Carrie S,Boucher Adam N,Jones G Morgan Journal of critical care PURPOSE:Propofol is one of the most commonly used sedatives in the intensive care unit (ICU) despite its undesirable hypotensive effects. The purpose of this study was to determine the effects of continuous intravenous (CIV) propofol on vasopressor requirements in mechanically ventilated patients with sepsis. MATERIALS AND METHODS:A multicenter, retrospective, propensity-matched pilot study was conducted comparing patients with sepsis or severe sepsis who received CIV propofol for sedation to those who did not. The primary outcome was incidence of vasopressor support. Secondary outcomes included change in mean arterial pressure, mortality, and length of stay. RESULTS:A total of 279 patients (149 CIV propofol, 130 non-CIV propofol) were evaluated, with 174 patients matched 1:1 based on propensity score. There was no difference in vasopressor support requirements (49.4% vs 54%; P= .65) or in those experiencing a greater than 20% decrease in mean arterial pressure from baseline (58.6% vs 63.2%; P= .53) in the CIV propofol and non-CIV propofol groups. Furthermore, there were no differences in any secondary outcomes including hospital mortality (32.2% vs 33.3%; P= .87). CONCLUSIONS:Continuous intravenous propofol for sedation did not increase vasopressor requirements in this septic population. Furthermore, CIV propofol was not associated with significant differences in the use of multiple vasopressors, change in mean arterial pressure, length of stay, or mortality. 10.1016/j.jcrc.2016.05.015
    Leaving more than your fingerprint on the intravenous line: a prospective study on propofol anesthesia and implications of stopcock contamination. Cole Devon C,Baslanti Tezcan Ozrazgat,Gravenstein Nikolaus L,Gravenstein Nikolaus Anesthesia and analgesia BACKGROUND:Acute care handling of IV stopcocks during anesthesia and surgery may result in contaminated IV tubing sets. In the context of widespread propofol use, a nutrient-rich hypnotic drug, we hypothesized that propofol anesthesia increases bacterial contamination of IV stopcocks and may compromise safety of IV tubing sets when continued to be used after propofol anesthesia. METHODS:We conducted an in vitro trial by collecting IV tubing sets at the time of patient discharge from same-day ambulatory procedures performed with and without propofol anesthesia. These extension sets were then held at room temperature for 6, 24, or 48 hours. We cultured 50 samples at each interval for both cohorts. Quantitative cultures were done by aspirating the IV stopcock dead space and plating the aspirate on blood agar for colony count and speciation. RESULTS:Positive bacterial counts were recovered from 17.3% of propofol anesthesia stopcocks (26/150) and 18.6% of nonpropofol stopcocks (28/150). At 6 hours, the average bacterial counts from stopcocks with visible residual propofol was 44 colony forming units (CFU)/mL, compared with 41 CFU/mL with no visible residual propofol and 37 CFU/mL in nonpropofol anesthesia stopcocks. There was a 100-fold increase in bacterial number in contaminated stopcock dead spaces at 48 hours after propofol anesthesia. This difference remained significant when comparing positive counts from stopcocks with no visible residual propofol and nonpropofol anesthesia (P = 0.034). CONCLUSIONS:There is a covert incidence and degree of IV stopcock bacterial contamination during anesthesia which is aggravated by propofol anesthetic. Propofol anesthesia may increase risk for postoperative infection because of bacterial growth in IV stopcock dead spaces. 10.1213/ANE.0b013e318292ed45
    Effects of sevoflurane and propofol on the development of pneumonia after esophagectomy: a retrospective cohort study. Zhang Guo-Hua,Wang Wen BMC anesthesiology BACKGROUND:Postoperative pneumonia (PP) is one of the common complications following esophagectomy and associated with poor short- and long-term outcomes. Sevoflurane and propofol, which have inflammatory-modulating effects, are common used general anesthetics. This study aimed to compare the effects of anesthesia with sevoflurane and propofol on the development of PP after esophageal surgery for cancer. METHODS:The electronic medical records of patients who underwent elective esophagectomy between July 2013 and July 2016 were reviewed. We conducted univariate and multivariate logistics analysis and propensity score matching analysis to compare the effect of sevoflurane and propofol on the incidence of PP and to identify the risk factors for PP after esophagectomy. RESULTS:Overall, the incidence of postoperative pneumonia was 9.5%. There was no significant difference in the rates of PP between sevoflurane group and propofol group either before or after propensity score matching (9.6% vs 8.0%, P = 0.606; 7.7% vs 6.4%, P = 0.754, respectively). Univariate and multivariate analysis revealed that alcohol use (OR 1.513; 95% CI 1.062-2.156), surgical procedure (Sweet: referent; Ivor-Lewis: OR 1.993; 95% CI 1.190-3.337; Three-incision: OR 1.878; 95% CI 1.296-2.722) and surgeon experience (high-volume: referent; low-volume: OR 1.525; 95% CI 1.090-2.135) were significant risk factors of postoperative pneumonia. CONCLUSIONS:Sevoflurane did not differ from propofol in terms of affecting the risk of PP development after esophagectomy. 10.1186/s12871-017-0458-4
    Propofol attenuates sepsis-induced acute kidney injury by regulating miR-290-5p/CCL-2 signaling pathway. Zheng Guodong,Qu Hong,Li Fen,Ma Weiquan,Yang Hong Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas Previous studies have indicated that propofol has immunomodulatory and antioxidative properties. However, the renoprotection effect and the precise mechanisms of propofol in sepsis-induced renal injury remain unclear. The purpose of the present study was to investigate the role of miR-290-5p/CCL-2 signaling in septic mice treatment with propofol. Mice were treated with propofol (50 mg/kg) twice within 24 h. Survival outcome was monitored within 48 h. The mRNA and protein levels were assayed by qRT-PCR and western blotting, respectively. Mouse podocytes (MPC5) were treated with lipopolysaccharide (LPS) to establish the cell model in vitro. The proliferation of MPC5 was monitored using the MTS assay. Cell apoptosis was analyzed by flow cytometry. Propofol improved survival outcome and alleviated acute kidney injury in cecal ligation and puncture-operated mice. Propofol increased miR-290-5p expression and decreased CCL-2 and inflammatory cytokines levels in the kidney for septic mice. We found that miR-290-5p was a direct regulator of CCL-2 in MPC5. Propofol could abrogate LPS-induced growth inhibition and apoptosis in MPC5. Meanwhile, propofol inhibited CCL-2 expression in LPS-treated MPC5, however, knockdown of miR-290-5p abrogated the inhibitory effect propofol on the mRNA and protein expressions of CCL-2. Propofol could serve as an effective therapeutic medication to suppress sepsis-induced renal injury in vivo and in vitro by regulating the miR-290-5p/CCL-2 signaling pathway. 10.1590/1414-431X20187655
    Liver nitrosation and inflammation in septic rats were suppressed by propofol via downregulating TLR4/NF-κB-mediated iNOS and IL-6 gene expressions. Wu Gong-Jhe,Lin Yung-Wei,Chuang Chi-Yuan,Tsai Hsiao-Chien,Chen Ruei-Ming Life sciences AIMS:Propofol can be applied as an anesthetic or sedative agent for septic patients. Our previous studies showed that propofol ameliorated inflammation- and nitrosative stress-induced cellular insults. This study further evaluated effects of propofol on cecal ligation and puncture (CLP)-induced septic insults to rats and its possible mechanisms. MAIN METHODS:Wistar rats were administered with CLP and effects of propofol on CLP-induced liver dysfunction and rat death were evaluated. Levels of hepatic or systemic nitrogen oxides (NOx) and interleukin (IL)-6 were quantified. Sequentially, inducible nitric oxide synthase (iNOS) and IL-6 gene expressions, toll-like receptor 4 (TLR4) protein levels, and nuclear factor (NF)-κB translocation were determined. KEY FINDINGS:Subjecting rats to CLP led to body weight loss, liver weight gain, and death. Administration of propofol lessened CLP-induced augmentations of serum and hepatic nitrosative stress and IL-6 levels. Additionally, propofol suppressed CLP-induced enhancements in levels of hepatic iNOS protein. Furthermore, the CLP-induced iNOS and IL-6 mRNA expressions in the liver were inhibited following propofol administration. Sequentially, subjecting rats to CLP enhanced hepatic TLR4 protein levels and NF-κB translocation to nuclei, but propofol inhibited these augmentations. SIGNIFICANCE:Consequently, exposure to propofol protected against CLP-induced liver dysfunction and increased the survival rates of the animals. This study shows that propofol can protect rats against septic insults through suppression of systemic and hepatic nitrosative and inflammatory stress due to inhibition of TLR4/NF-κB-mediated iNOS and IL-6 mRNA and protein expressions. 10.1016/j.lfs.2018.01.005
    The Effect of Propofol and Dexmedetomidine Sedation on Norepinephrine Requirements in Septic Shock Patients: A Crossover Trial. Morelli Andrea,Sanfilippo Filippo,Arnemann Philip,Hessler Michael,Kampmeier Tim G,D'Egidio Annalia,Orecchioni Alessandra,Santonocito Cristina,Frati Giacomo,Greco Ernesto,Westphal Martin,Rehberg Sebastian W,Ertmer Christian Critical care medicine OBJECTIVES:Propofol-based sedation may increase hemodynamic instability by decreasing vascular tone and venous return. Incremental exogenous catecholamines doses may be required to counteract such effects, aggravating the deleterious effects of sympathetic overstimulation. α-2 adrenergic agonists have been reported to decrease norepinephrine requirements in experimental septic shock. The aim of the present study is to test the hypothesis that switching from sedation with propofol to the α-2 agonist dexmedetomidine may decrease norepinephrine doses in septic shock. DESIGN:Prospective open-label crossover study. SETTINGS:University hospital, ICU. PATIENTS:Thirty-eight septic shock patients requiring norepinephrine to maintain adequate mean arterial pressure and needing deep sedation with propofol and remifentanil to maintain a Richmond Agitation-Sedation Scale score between -3 and -4. INTERVENTIONS:An initial set of measurements including hemodynamics, norepinephrine doses, and depth of sedation were obtained during sedation with propofol. Propofol was then replaced by dexmedetomidine and a second set of data was obtained after 4 hours of dexmedetomidine infusion. Sedation was switched back to propofol, and a final set of measurements was obtained after 8 hours. A Richmond Agitation-Sedation Scale score between -3 and -4 was maintained during the study period. MEASUREMENTS AND MAIN RESULTS:Norepinephrine requirements decreased from 0.69 ± 0.72 μg/kg/min before dexmedetomidine to 0.30 ± 0.25 μg/kg/min 4 hours after dexmedetomidine infusion, increasing again to 0.42 ± 0.36 μg/kg/min while on propofol 8 hours after stopping dexmedetomidine (p < 0.005). Dexmedetomidine dosage was 0.7 ± 0.2 μg/kg/hr. Before and after dexmedetomidine infusion, sedative doses remained unchanged (propofol 2.6 ± 1.2 vs 2.6 ± 1.2 mg/kg/hr; p = 0.23 and remifentanil 1.27 ± 0.17 vs 1.27 ± 0.16 μg/kg/hr; p = 0.52, respectively). Richmond Agitation-Sedation Scale was -4 (-4 to -3) before, -4 (-4 to -3) during, and -4 (-4 to -4) after dexmedetomidine (p = 0.07). CONCLUSIONS:For a comparable level of sedation, switching from propofol to dexmedetomidine resulted in a reduction of catecholamine requirements in septic shock patients. 10.1097/CCM.0000000000003520
    [Drugs for intravenous induction of anesthesia: propofol]. Bolkenius D,Dumps C,Halbeck E Der Anaesthesist In a series of articles dealing with hypnotics for induction of anesthesia, this article describes the development and current value of propofol. Its significance far exceeds that of a pure induction hypnotic (sedation in diagnostic and therapeutic procedures and on the intensive care unit). Propofol is also used for sedation in diagnostic and therapeutic procedures and on the intensive care unit. In the field of induction of anesthesia, the alternatives are barely used. Some contraindications are still controversial whereas others are no longer sufficiently anchored in the users' awareness (widespread off-label use). Adverse effects, such as injection pain, infection risk and propofol-related infusion syndrome (PRIS) could be significantly reduced by pharmacovigilance. With appropriate caution nearly the whole spectrum of anesthesiology patients can be treated using propofol. The hemodynamic side effects and the rare but potentially fatal PRIS are limitations. Further developments address the water solubility and the solubilizing agents of propofol. 10.1007/s00101-017-0397-y
    Impact of general anaesthesia on endoplasmic reticulum stress: propofol isoflurane. Seo Eun-Hye,Piao Liyun,Park Hyun-Jun,Lee Ji Yeon,Sa Mijung,Oh Chung-Sik,Lee Seung-Hyun,Kim Seong-Hyop International journal of medical sciences : This study investigated the effects of propofol and isoflurane on endoplasmic reticulum (ER) stress in an animal model under general anaesthesia. : Rats were randomly divided into Propofol and Isoflurane groups. Anaesthesia was maintained with propofol for Propofol group or isoflurane for Isoflurane group during 3 h. ER stress from lymphocytes in blood and tissues was evaluated between two groups after euthanasia. Reactive oxygen species (ROS) from lymphocytes in blood and tissues, and cytokines in blood were also checked. An immunohistochemical assay for ER stress marker from tissues was performed. : After anaesthesia, the levels of CCAAT-enhancer-binding protein homologous proteins (CHOP) in blood and liver were significantly higher in Isoflurane group, compared to Propofol group [blood, 31,499 ± 4,934 (30,733, 26,441-38,807) mean fluorescence intensity (MFI) in Isoflurane group 20,595 ± 1,838 (20,780, 18,866-22,232) MFI in Propofol group, = 0.002; liver, 28,342 ± 5,535 (29,421, 23,388-32,756) MFI in Isoflurane group 20,004 ± 2,155 (19,244, 18,197-22,191) MFI in Propofol group, = 0.020]. ROS in blood was significantly higher in Isoflurane group, compared to Propofol group. However, cytokines in blood and immunohistochemical assays in tissues were similar between groups. : Significant higher of ER stress from blood and liver were observed in rats under anaesthesia with isoflurane, compared to those that received propofol. ROS from blood also showed significant higher under anaesthesia with isoflurane. However, these findings were not associated with any changes in cytokines in blood or immunohistochemical assay in tissues. 10.7150/ijms.36265
    Sepsis-induced liver dysfunction was ameliorated by propofol via suppressing hepatic lipid peroxidation, inflammation, and drug interactions. Wu Gong-Jhe,Lin Yung-Wei,Tsai Hsiao-Chien,Lee Yuan-Wen,Chen Jui-Tai,Chen Ruei-Ming Life sciences AIMS:Our previous study showed that propofol can protect against sepsis-induced insults through suppressing liver nitrosation and inflammation. This study further evaluated the mechanisms of propofol-caused protection from sepsis-induced liver dysfunction. MAIN METHODS:Male Wistar rats were subjected to cecal ligation and puncture (CLP) and then exposed to propofol. Levels of hepatic oxidative stress and lipid peroxidation were consecutively measured. Expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-4 messenger (m)RNA or proteins were quantified. Effects of propofol on microsomal pentoxyresorufin O-dealkelase (PROD) and ethoxycoumarin O-deethylase (ECOD) activities were determined. KEY FINDINGS:Administration of propofol to CLP-treated rats significantly attenuated sepsis-induced insults. CLP caused augmented serum aspartate aminotransferase and alanine aminotransferase activities and concurrently triggered liver damage. In contrast, treatment with propofol protected against CLP-induced liver dysfunction. As to the mechanisms, the CLP-induced increases in oxidative stress and lipid peroxidation levels and TNF-α and IL-1β mRNA and protein expressions were subsequently attenuated by propofol. Furthermore, administration of CLP-treated rats with propofol augmented levels of IL-4 in the liver. Phenobarbital treatment of liver microsomes in CLP-treated rats produced less amplification of PROD and ECOD activities, and a smaller amount of 4-hydroxypropofol was metabolized from propofol by liver microsomes. In contrast, more drug interactions occurred with propofol, which decreased PROD and ECOD activities in liver microsomes of CLP-treated rats. SIGNIFICANCE:Taken together, the present study showed that propofol can protect against sepsis-induced liver dysfunction through suppressing hepatic oxidative stress, lipid peroxidation, inflammation, and drug biotransformation and interactions in the liver. 10.1016/j.lfs.2018.10.038
    Propofol inhibits endogenous formyl peptide-induced neutrophil activation and alleviates lung injury. Chen Chun-Yu,Tsai Yung-Fong,Huang Wei-Ju,Chang Shih-Hsin,Hwang Tsong-Long Free radical biology & medicine Critically ill patients have a high risk of sepsis. Various studies have demonstrated that propofol has anti-inflammatory effects that may benefit critically ill patients who require anesthesia. However, the mechanism and therapeutic effect remain incompletely understood. Our previous data suggest that propofol can act as a formyl peptide receptor 1 (FPR1) antagonist. Here, we hypothesize that propofol mitigates sepsis-induced acute lung injury (ALI) by inhibiting mitochondria-derived N-formyl peptide-mediated neutrophil activation. Oxidative stress caused by activated neutrophils is involved in the pathogenesis of ALI. In human neutrophils, propofol competitively reduced the release of superoxide and associated reactive oxygen species induced by fMMYALF, a human mitochondria-derived N-formyl peptide, suggesting that propofol effectively suppresses neutrophilic oxidative stress. In addition, propofol significantly inhibited fMMYALF-induced elastase release, chemotaxis, calcium mobilization, and phosphorylation of protein kinase B and mitogen-activated protein kinases. These results indicate that propofol suppresses neutrophil activation by blocking the interaction between endogenous N-formyl peptide and its receptor, FPR1, thus inhibiting downstream signaling. Furthermore, propofol alleviated alveolar wall disruption, edematous changes, and neutrophil infiltration in lipopolysaccharide-induced ALI in mice. Noticeably, propofol improved the survival of sepsis mice. This study indicates that the anti-neutrophil effects of propofol may benefit critically ill septic patients. 10.1016/j.freeradbiomed.2018.09.048
    Growth of Microorganisms in Propofol and Mixture of Propofol, Lidocaine and Fentanyl. Altan Hatice Aysel,Bonabi Esat,Kesici Sevgi,Sezer Hafize,Ucar Veli Bulent Journal of the College of Physicians and Surgeons--Pakistan : JCPSP OBJECTIVE:To determine the growth of microorganisms in propofol when combined with fentanyl and lidocaine in different temperatures and times in order to find out whether there is any improvement in antimicrobial effect to lengthen the safe duration of time for application of propofol. STUDY DESIGN:Cross-sectional study. PLACE AND DURATION OF STUDY:Istanbul Aydin University Laboratory, Istanbul, Turkey, from June to September 2018. METHODOLOGY:The studied drugs and thier combination was used to determine their effect on bacterial growth of Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans and Acinetobacter baumanni. Bacterial solutions were prepared at 0.5 MacFarland in sterile 0.9% physiological saline and diluted at 1:100 concentration. Colony numbers were measured as colony forming units mL-1 at 0, 8, and 24 hours and at 4oC, 22oC and 37oC. RESULTS:In general, propofol supported the growth of microorganisms. Fentanyl with propofol also promoted the growth, especially in room and body temperature at 8th and 24th hours but when combined with lidocaine, the number of CFUs was reduced significantly compared with propofol + fentanyl group. Lidocaine inhibited the growth of microorganisms in all the solutions except for candida albicans. CONCLUSION:Lidocaine was shown to have antibacterial effect which carries advantage for inhibiting infections due to propofol; but aseptic technique is essential during preparation of propofol infusions. Fentanyl like propofol also promoted the growth at room and body temperatures. 10.29271/jcpsp.2019.09.828
    [The antimicrobial activity of ephedrine and admixture of ephedrine and propofol: an in vitro study]. Tulgar Serkan,Alasehir Elcin Akduman,Selvi Onur Revista brasileira de anestesiologia INTRODUCTION:Propofol and Ephedrine are commonly used during anesthesia maintenance, the former as a hypnotic agent and the later as a vasopressor. The addition of propofol to ephedrine or administration of ephedrine before propofol injection is useful for decreasing or preventing propofol related hemodynamic changes and vascular pain. This in vitro study evaluated the antibacterial effect on common hospital-acquired infection pathogens of ephedrine alone or combined with propofol. MATERIAL AND METHOD:The study was performed in two stages. In the first, the Minimum Inhibitory Concentration of propofol and ephedrine alone and combined was calculated for Escherichia coli, Enterococcus faecium, Staphylococcus aureus, Pseudomonas aeruginosa, and a clinical isolate of Acinetobacter spp. at 0, 6, 12 and 24h, using the microdilution method. In the second stage, the same drugs and combination were used to determine their effect on bacterial growth. Bacterial solutions were prepared at 0.5MacFarland in sterile 0.9% physiological saline and diluted at 1/100 concentration. Colony numbers were measured as colony forming units.mL at 0, 2, 4, 6, 8, 10 and 12th hours. RESULTS:Ephedrine either alone or combined with propofol did not have an antimicrobial effect on Escherichia coli, Enterococcus faecium or Pseudomonas aeruginosa and this was similar to propofol. However, ephedrine alone and combined with propofol was found to have an antimicrobial effect on Staphylococcus aureus and Acinetobacter species at 512mcg.mL concentration and significantly decreased bacterial growth rate. CONCLUSION:Ephedrine has an antimicrobial activity on Staphylococcus aureus and Acinetobacter species which were frequently encountered pathogens as a cause of nosocomial infections. 10.1016/j.bjan.2017.08.001
    Infectious Disease Risk Associated with Contaminated Propofol Anesthesia, 1989-2014(1). Zorrilla-Vaca Andrés,Arevalo Jimmy J,Escandón-Vargas Kevin,Soltanifar Daniel,Mirski Marek A Emerging infectious diseases Administration of propofol, the most frequently used intravenous anesthetic worldwide, has been associated with several iatrogenic infections despite its relative safety. Little is known regarding the global epidemiology of propofol-related outbreaks and the effectiveness of existing preventive strategies. In this overview of the evidence of propofol as a source of infection and appraisal of preventive strategies, we identified 58 studies through a literature search in PubMed, Embase, and Lilacs for propofol-related infections during 1989-2014. Twenty propofol-related outbreaks have been reported, affecting 144 patients and resulting in 10 deaths. Related factors included reuse of syringes for multiple patients and prolonged exposure to the environment when vials were left open. The addition of antimicrobial drugs to the emulsion has been instituted in some countries, but outbreaks have still occurred. There remains a lack of comprehensive information on the effectiveness of measures to prevent future outbreaks. 10.3201/eid2206.150376
    Serratia marcescens sepsis outbreak caused by contaminated propofol. Cilli Feriha,Nazli-Zeka Arzu,Arda Bilgin,Sipahi Oguz Resat,Aksit-Barik Sukran,Kepeli Nurhayat,Ozinel Mehmet Ali,Gulay Zeynep,Ulusoy Sercan American journal of infection control We presented a sepsis outbreak caused by Serratia marcescens from contaminated propofol to raise awareness. Three patients had sepsis syndrome after chest surgery. Isolation of S marcescens from patients' respiratory and blood samples alerted us to a possible outbreak. Four syringes filled with propofol and 1 saline solution yielded S marcescens. Nine of 10 isolates from samples of patients and environment genotyped by pulsed-field gel electrophoresis were the same. Disobeying aseptic injection rules of propofol is still causing outbreaks. 10.1016/j.ajic.2018.10.014
    Propofol specifically suppresses IL-1β secretion but increases bacterial survival in Staphylococcus aureus-infected RAW264.7 cells. Chen Ming-Shan,Lin Wen-Chun,Yeh Hsuan-Te,Hu Chia-Lin,Sheu Shew-Meei Molecular and cellular biochemistry Anesthetics have immunomodulatory effects, but the use of different assay systems has contributed to inconsistent results in the literature. IL-1β and reactive oxygen species (ROS) secreted by phagocytes are important factors that protect against Staphylococcus aureus infection. In this study, the effects of four intravenous anesthetics (propofol, thiamylal sodium, midazolam, and ketamine) on IL-1β secretion, ROS, and bacterial survival in S. aureus-infected RAW264.7 cells were evaluated. S. aureus-infected RAW264.7 cells with or without intravenous anesthetic treatment were established as the experimental model. Cell supernatants were subjected to ELISAs to measure secreted IL-1β. Cell pellets were subjected to qPCR and western blot analyses to analyze IL-1β mRNA and protein levels. Luminol chemiluminescence assays were used to detect ROS, and bacterial survival was determined by counting the colony forming units at the beginning and end of the infection. Compared with the levels after treatment with the other intravenous anesthetics, secreted IL-1β levels were lowest in the supernatant of S. aureus-infected RAW264.7 cell cultures after propofol treatment, but propofol did not decrease IL-1β mRNA or protein expression. However, thiamylal sodium and midazolam decreased IL-1β mRNA and protein expression in a dose-dependent manner. Additionally, propofol substantially decreased S. aureus-stimulated ROS and phagocytosis. Bacterial survival was strongly increased by propofol treatment. Of the four intravenous anesthetics, propofol was the most potent inhibitor of IL-1β secretion and ROS level in S. aureus-infected RAW264.7 cells; moreover, propofol resulted in an increase in bacterial survival by inhibiting ROS and phagocytosis. 10.1007/s11010-018-3348-2
    Propofol Sedation Exacerbates Kidney Pathology and Dissemination of Bacteria during Staphylococcus aureus Bloodstream Infections. Visvabharathy Lavanya,Freitag Nancy E Infection and immunity Methicillin-resistant (MRSA) is responsible for large numbers of postsurgical nosocomial infections across the United States and worldwide. Propofol anesthesia is widely used in surgery and in intensive care units, and recent evidence indicates that even brief exposure to propofol can substantially increase host susceptibility to microbial infection. Here, we delineate the impact of propofol sedation on MRSA bloodstream infections in mice in the presence and absence of prophylactic antibiotic treatment. Consistent with previous reports, brief periods of anesthesia with propofol were sufficient to significantly increase bacterial burdens and kidney pathology in mice infected with MRSA. Propofol exposure increased neutrophilic infiltrates into the kidney and enhanced bacterial dissemination throughout kidney tissue. Propofol sedation reduced populations of effector phagocytes and mature dendritic cells within the kidney and led to the apparent expansion of myeloid-derived suppressor cell-like populations. When propofol was coadministered with vancomycin prophylaxis, it dramatically increased kidney abscess formation and bacterial dissemination throughout kidney tissue at early times post- infection compared to antibiotic-treated but nonsedated animals. Taken together, our data indicate that short-term sedation with propofol significantly increases the severity of bloodstream MRSA infection, even when administered in conjunction with vancomycin prophylaxis. 10.1128/IAI.00097-17
    Propofol Increases Host Susceptibility to Microbial Infection by Reducing Subpopulations of Mature Immune Effector Cells at Sites of Infection. Visvabharathy Lavanya,Xayarath Bobbi,Weinberg Guy,Shilling Rebecca A,Freitag Nancy E PloS one Anesthetics are known to modulate host immune responses, but separating the variables of surgery from anesthesia when analyzing hospital acquired infections is often difficult. Here, the bacterial pathogen Listeria monocytogenes (Lm) was used to assess the impact of the common anesthetic propofol on host susceptibility to infection. Brief sedation of mice with physiologically relevant concentrations of propofol increased bacterial burdens in target organs by more than 10,000-fold relative to infected control animals. The adverse effects of propofol sedation on immune clearance of Lm persisted after recovery from sedation, as animals given the drug remained susceptible to infection for days following anesthesia. In contrast to propofol, sedation with alternative anesthetics such as ketamine/xylazine or pentobarbital did not increase susceptibility to systemic Lm infection. Propofol altered systemic cytokine and chemokine expression during infection, and prevented effective bacterial clearance by inhibiting the recruitment and/or activity of immune effector cells at sites of infection. Propofol exposure induced a marked reduction in marginal zone macrophages in the spleens of Lm infected mice, resulting in bacterial dissemination into deep tissue. Propofol also significantly increased mouse kidney abscess formation following infection with the common nosocomial pathogen Staphylococcus aureus. Taken together, these data indicate that even brief exposure to propofol severely compromises host resistance to microbial infection for days after recovery from sedation. 10.1371/journal.pone.0138043
    Suspected periprosthetic joint infection after total knee arthroplasty under propofol versus sevoflurane anesthesia: a retrospective cohort study. Kishimoto Miwa,Yamana Hayato,Inoue Satoki,Noda Tatsuya,Akahane Manabu,Inagaki Yusuke,Matsui Hiroki,Yasunaga Hideo,Kawaguchi Masahiko,Imamura Tomoaki Canadian journal of anaesthesia = Journal canadien d'anesthesie PURPOSE:Periprosthetic joint infection is a serious complication of total knee arthroplasty. Though there are many factors that might increase its risk, the use of propofol for maintaining general anesthesia could theoretically increase the incidence of infection because of its lipid component that supports bacterial growth. Nevertheless, the relationship between anesthetic maintenance agents and the occurrence of periprosthetic joint infection remains uncertain. The purpose of this study was to compare the incidence of suspected early-onset periprosthetic joint infection between patients undergoing total knee arthroplasty under propofol vs sevoflurane anesthesia. METHODS:We conducted a retrospective cohort study of patients in the national inpatient Diagnosis Procedure Combination database in Japan who underwent total knee arthroplasty. Suspected periprosthetic joint infection was surrogately defined as the need for arthrocentesis or debridement within 30 days of surgery. Propensity score matching was performed between patients who received either propofol or sevoflurane for anesthetic maintenance to determine the proportion of those with infection. RESULTS:Eligible patients (n = 21,899) were categorized into either the propofol (n = 7,439) or sevoflurane (n = 14,460) groups. In the 5,140 propensity-matched patient pairs, there was no significant difference in the proportion of arthrocentesis or debridement [1.3% propofol vs 1.7% sevoflurane; respectively (relative risk, 0.76; 95% CI, 0.55 to 1.04; P = 0.10)] between the groups. The mean (SD) length of stay in the propofol group was significantly longer than in the sevoflurane group [32.5 (18.4) days vs 31.4 (14.4) days, respectively; mean difference, 1.1; 95% CI, 0.5 to 1.8; P < 0.001]. CONCLUSION:Propensity score analysis suggested no significant association between the choice of anesthetic maintenance agent and the occurrence of suspected early-onset periprosthetic joint infection in patients undergoing total knee arthroplasty. 10.1007/s12630-018-1139-6