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Relland LM, Hall M, Martin DP, Nateri J, Hanson-Huber L, Beebe A, Samora W, Klamar J, Muszynski J, Tobias JD. Immune Function following Major Spinal Surgery and General Anesthesia. J Pediatr Intensive Care 2020; 10:248-255. [PMID: 34745697 DOI: 10.1055/s-0040-1716668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Accepted: 08/06/2020] [Indexed: 10/23/2022] Open
Abstract
There are reported differences in the effects that general anesthetics may have on immune function after minor surgery. To date, there are no prospective trials comparing total intravenous anesthesia (TIVA) with a volatile agent-based technique and its effects on immune function after major spinal surgery in adolescents. Twenty-six adolescents undergoing spinal fusion were randomized to receive TIVA with propofol-remifentanil or a volatile agent-based technique with desflurane-remifentanil. Immune function measures were based on the antigen-presenting and cytokine production capacity, and relative proportions of cell populations. Overall characteristics of the two groups did not differ in terms of perioperative times, hemodynamics, or fluid shifts, but those treated with propofol had lower bispectral index values. Experimental groups had relatively high baseline interleukin-10 values, but both showed a significant inflammatory response with similar changes in their respective immune functions. This included a shift toward a granulocytic predominance; a transient reduction in monocyte markers with significant decrease in antigen-presenting capacity and cytokine production capacity. Anesthetic choice does not appear to differentially impact immune function, but exposure to anesthetics and surgical trauma results in reproducibly measurable suppression of both innate and adaptive immunity in adolescents undergoing posterior spinal fusion. The magnitude of this suppression was modest when compared with pediatric and adult patients with critical illnesses. This study highlighted the need to evaluate immune function in a broader population of surgical patients with higher severity of illness.
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Affiliation(s)
- Lance M Relland
- Department of Anesthesiology & Pain Medicine, Nationwide Children's Hospital, Columbus, Ohio, United States.,Center for Clinical and Translational Research, Nationwide Children's Hospital, Columbus, Ohio, United States
| | - Mark Hall
- Center for Clinical and Translational Research, Nationwide Children's Hospital, Columbus, Ohio, United States.,Department of Pediatrics, Division of Critical Care, Nationwide Children's Hospital, Columbus, Ohio, United States
| | - David P Martin
- Department of Anesthesiology & Pain Medicine, Nationwide Children's Hospital, Columbus, Ohio, United States
| | - Jyotsna Nateri
- Center for Clinical and Translational Research, Nationwide Children's Hospital, Columbus, Ohio, United States
| | - Lisa Hanson-Huber
- Center for Clinical and Translational Research, Nationwide Children's Hospital, Columbus, Ohio, United States
| | - Allan Beebe
- Department of Orthopedic Surgery, Nationwide Children's Hospital, Columbus, Ohio, United States
| | - Walter Samora
- Department of Orthopedic Surgery, Nationwide Children's Hospital, Columbus, Ohio, United States
| | - Jan Klamar
- Department of Orthopedic Surgery, Nationwide Children's Hospital, Columbus, Ohio, United States
| | - Jennifer Muszynski
- Center for Clinical and Translational Research, Nationwide Children's Hospital, Columbus, Ohio, United States.,Department of Pediatrics, Division of Critical Care, Nationwide Children's Hospital, Columbus, Ohio, United States
| | - Joseph D Tobias
- Department of Anesthesiology & Pain Medicine, Nationwide Children's Hospital, Columbus, Ohio, United States
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Propofol specifically suppresses IL-1β secretion but increases bacterial survival in Staphylococcus aureus-infected RAW264.7 cells. Mol Cell Biochem 2018; 449:117-125. [PMID: 29667111 PMCID: PMC6223810 DOI: 10.1007/s11010-018-3348-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2017] [Accepted: 04/05/2018] [Indexed: 11/14/2022]
Abstract
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.
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Heil LBB, Silva PL, Pelosi P, Rocco PRM. Immunomodulatory effects of anesthetics in obese patients. World J Crit Care Med 2017; 6:140-152. [PMID: 28828299 PMCID: PMC5547428 DOI: 10.5492/wjccm.v6.i3.140] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2017] [Revised: 04/27/2017] [Accepted: 07/10/2017] [Indexed: 02/06/2023] Open
Abstract
Anesthesia and surgery have an impact on inflammatory responses, which influences perioperative homeostasis. Inhalational and intravenous anesthesia can alter immune-system homeostasis through multiple processes that include activation of immune cells (such as monocytes, neutrophils, and specific tissue macrophages) with release of pro- or anti-inflammatory interleukins, upregulation of cell adhesion molecules, and overproduction of oxidative radicals. The response depends on the timing of anesthesia, anesthetic agents used, and mechanisms involved in the development of inflammation or immunosuppression. Obese patients are at increased risk for chronic diseases and may have the metabolic syndrome, which features insulin resistance and chronic low-grade inflammation. Evidence has shown that obesity has adverse impacts on surgical outcome, and that immune cells play an important role in this process. Understanding the effects of anesthetics on immune-system cells in obese patients is important to support proper selection of anesthetic agents, which may affect postoperative outcomes. This review article aims to integrate current knowledge regarding the effects of commonly used anesthetic agents on the lungs and immune response with the underlying immunology of obesity. Additionally, it identifies knowledge gaps for future research to guide optimal selection of anesthetic agents for obese patients from an immunomodulatory standpoint.
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Aguirre JA, Lucchinetti E, Clanachan AS, Plane F, Zaugg M. Unraveling Interactions Between Anesthetics and the Endothelium. Anesth Analg 2016; 122:330-48. [DOI: 10.1213/ane.0000000000001053] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Celik MG, Saracoglu A, Saracoglu T, Kursad H, Dostbil A, Aksoy M, Ahiskalioglu A, Ince I. Effects of Propofol and Midazolam on the Inflammation of Lungs after Intravenous Endotoxin Administration in Rats. Eurasian J Med 2015; 47:109-14. [PMID: 26180495 PMCID: PMC4494545 DOI: 10.5152/eajm.2014.70] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2014] [Accepted: 10/30/2014] [Indexed: 11/22/2022] Open
Abstract
OBJECTIVE Pulmonary complications are important sepsis (such as ARDS, diffuse pneumonia). Acute respiratory distress syndrome (ARDS) is characterized by the extensive migration of neutrophils into alveoli of the lungs. Propofol and midazolam are the most widely used agents for sedation in intensive care units. Aimed to investigate the effects of anaesthesia with propofol and midazolam on measured hemodynamic variables and neutrophil migration induced by Escherichia Coli endotoxin (ECE) in pulmonary viscera. MATERIALS AND METHODS Forty Sprague Dawley male rats were randomly assigned to four groups: Thiopental Sodium 30 mg/kg was administered intraperitoneally to anesthetize the rats. They were ventilated via tracheotomy. Femoral artery was cannulated for the measurement of continuous blood pressure and gases. Group C was the control. After the administration of 1 mL/kg 0.9% NaCL, infusion began at 1 mL/kg/h rate. In Group E 15 mg/kg lipopolysaccharide derived from ECE was administered iv. In Group PE, after a bolus dose of 10 mg/kg propofol and 15 mg/kg ECE, 10 mg/kg/h infusion was applied. In Group ME, after 0.1 mg/kg midazolam bolus dose and 15 mg/kg ECE administration, 0.1 mg/kg/h infusion was administered iv. Rats were sacrified by iv potassium chloride. The lungs were then removed, fixed in 10% buffered formalin for 3 days and embedded in paraffin. They were graded on a scale of 0-3 according to the aggregation of neutrophils. RESULTS There was intense neutrophil migration in Group E (grade 2, 3). However, although mild neutrophil migration was obtained in 70% of the rat lungs in Group ME (grade 1, 2), it was recorded in only 30% of Group PE (grade 1). CONCLUSION The sepsis model induced by ECE and compared with midazolam, propofol anaesthesia is associated with less neutrophil infiltration. In the light of the literature, propofol attenuate the free-radical-mediated lipid peroxidation and systemic inflammation in patients.
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Affiliation(s)
- Mine Gursac Celik
- Department of Anesthesiology and Reanimation Anesthesia, Ataturk University Faculty of Medicine, Erzurum, Turkey
| | - Ayten Saracoglu
- Department of Anaesthesiology, Marmara University Faculty of Medicine, Istanbul, Turkey
| | - Tolga Saracoglu
- Department of Anaesthesiology, Marmara University Faculty of Medicine, Istanbul, Turkey
| | - Husnu Kursad
- Department of Anesthesiology and Reanimation Anesthesia, Ataturk University Faculty of Medicine, Erzurum, Turkey
| | - Aysenur Dostbil
- Department of Anesthesiology and Reanimation Anesthesia, Ataturk University Faculty of Medicine, Erzurum, Turkey
| | - Mehmet Aksoy
- Department of Anesthesiology and Reanimation Anesthesia, Ataturk University Faculty of Medicine, Erzurum, Turkey
| | - Ali Ahiskalioglu
- Department of Anesthesiology and Reanimation Anesthesia, Ataturk University Faculty of Medicine, Erzurum, Turkey
| | - Ilker Ince
- Department of Anesthesiology and Reanimation Anesthesia, Ataturk University Faculty of Medicine, Erzurum, Turkey
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Choe WJ, Kim JH, Park SY, Kim J. Electromyographic response of facial nerve stimulation under different levels of neuromuscular blockade during middle-ear surgery. J Int Med Res 2013; 41:762-70. [PMID: 23660086 DOI: 10.1177/0300060513484435] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
OBJECTIVE To investigate facial nerve monitoring in patients receiving the partial nondepolarizing neuromuscular blocking agents (NMBAs), remifentanil and propofol. METHODS Patients with normal facial function and advanced middle-ear disease were enrolled. For total intravenous anaesthesia (TIVA), propofol and remifentanil were infused as induction/maintenance anaesthesia. Stimulation thresholds and amplitudes were recorded at each train-of-four (TOF) nerve stimulation level. Time differences between start of TOF and electromyographic (EMG) amplitude decreases (Ti), and between complete recovery of TOF and EMG amplitudes (Tr), were calculated. RESULTS Fifteen patients were enrolled. Mean ± SD Ti was 3.4 ± 1.28 min; Tr was 18.7 ± 4.41 min. Amplitude of stimulation was apparent mostly at TOF level 1. In most cases, no or a weak response (<100 µV) was observed at TOF 0. Mean ± SD threshold of electrical stimulation was 0.31 ± 0.10 mA at TOF 1. At TOF > 2, all cases showed EMG response on electrical stimulation. CONCLUSIONS Induction of TIVA using propofol and remifentanil provided reliable conditions for delicate microsurgery. Minimal NMBA use, considered as producing TOF levels >1, was sufficient for facial nerve monitoring in neuro-otological surgery.
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Affiliation(s)
- Won Joo Choe
- Department of Anaesthesiology and Pain Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Gyeonggi-do, Republic of Korea
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Effects of desflurane, sevoflurane and propofol on phagocytosis and respiratory burst activity of human polymorphonuclear leucocytes in bronchoalveolar lavage. Eur J Anaesthesiol 2009; 26:150-4. [PMID: 19142090 DOI: 10.1097/eja.0b013e328319bfeb] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND AND OBJECTIVE In polymorphonuclear leucocytes, phagocytosis and respiratory burst activity are mainly responsible for bacterial killing. We aimed to investigate the effects of anaesthesia with desflurane, sevoflurane and propofol on these functional activities of polymorphonuclear leucocytes in bronchoalveolar lavage fluid. METHODS Sixty patients scheduled to have tympanoplasty surgery were studied. The patients were divided into three groups (group D, desflurane; group S, sevoflurane; group P, propofol). Anaesthesia was induced with propofol, fentanyl and rocuronium in all groups. Anaesthesia was maintained with inhalation agent or propofol. Bronchoalveolar lavage was performed immediately after induction of anaesthesia and after surgical procedure by a fibreoptic bronchoscope. Leucocyte respiratory burst and phagocytic activity in bronchoalveolar lavage fluid were determined by flow cytometric analysis of gated leucocyte populations within 2 h after each bronchoalveolar lavage sample. Changes in leucocyte functions with time were expressed as mean fluorescence intensity. RESULTS There were no significant differences in phagocytic activity of polymorphonuclear leucocytes within and between the groups. The respiratory burst function of polymorphonuclear leucocytes showed a significant increase after surgery in group P (P < 0.05). When we compared the differences between the three groups, we found the difference in mean fluorescence intensity as statistically significant between group P and group S. CONCLUSION This study showed that propofol anaesthesia increased the respiratory burst function of polymorphonuclear leucocytes in bronchoalveolar lavage fluid.
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Clinical Comparison between Barbiturate and Propofol Coma Therapy in the Patients with Severe Traumatic Brain Injury. ACTA ACUST UNITED AC 2008. [DOI: 10.13004/jknts.2008.4.1.24] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Huettemann E, Jung A, Vogelsang H, Hout NV, Sakka SG. Effects of propofol vs methohexital on neutrophil function and immune status in critically ill patients. J Anesth 2006; 20:86-91. [PMID: 16633763 DOI: 10.1007/s00540-005-0377-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2005] [Accepted: 12/23/2005] [Indexed: 12/13/2022]
Abstract
PURPOSE Patients with severe brain injury often require long-term sedation and have a high incidence of nosocomial infections, causing an increased mortality rate. However, whether anesthetic drugs might contribute to immunosuppressive effects remains unclear. METHODS In this prospective study, we investigated the effects of propofol (4-6 mg x kg(-1) x h(-1)) and methohexital (1-3 mg x kg(-1) x h(-1)) on neutrophil leukocyte function and immune status in 21 patients with brain injury who either received propofol (n = 12; 9 male, 3 female; mean age, 51 +/- 15 years) or methohexital (n = 9; 8 male, 1 female; mean age, 48 +/- 17 years) after admission to the intensive care unit (ICU). Both sedatives were administered over 7 days and individual dosage was adapted according to clinical requirements. Neutrophil leukocyte function was assessed as phagocytosis and respiratory oxidative burst activity. Furthermore, leukocyte subpopulations, and surface markers of lymphocytes and monocytes (CD3; CD4; CD45RO; CD4/CD45RO; CD25; CD4 and CD25; CD54; CD69; CD14/HLA-DR; CD8; CD3/HLA-DR; CD4 : CD8 ratio) were assessed. Blood samples were drawn on ICU admission, and on days 3, 7, and 14. Patients' demographics were compared by Wilcoxon test and laboratory results were compared by analysis of variance (ANOVA) for repeated measurements, with an all pairwise multiple comparison procedure. RESULTS There were no significant differences in neutrophil oxidative burst and phagocytosis within or between the two groups at the different time points. With respect to cellular markers of lymphocytes and monocytes, all values throughout remained in the normal range. CONCLUSION Methohexital and propofol exhibited no significant effects on neutrophil function and immune status in patients with severe brain injury requiring long-term sedation.
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Affiliation(s)
- Egbert Huettemann
- Department of Anesthesiology and Intensive Care Medicine, Friedrich-Schiller-University, Erlanger Allee 101, D-07747 Jena, Germany
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Ploppa A, Kiefer RT, Nohé B, Haeberle HA, Dieterich HJ, Unertl KE, Krueger WA. Dose-dependent influence of barbiturates but not of propofol on human leukocyte phagocytosis of viable Staphylococcus aureus. Crit Care Med 2006; 34:478-83. [PMID: 16424731 DOI: 10.1097/01.ccm.0000199067.71968.6e] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE Deep sedation with barbiturates or propofol is a standard therapy for patients with critically elevated intracranial pressure. Such patients are prone to infectious complications, especially to pneumonias, which are most commonly caused by Staphylococcus aureus. Although various immunomodulatory effects of barbiturates have been described in vitro, their influence on the phagocytosis of viable S. aureus has yet to be investigated. Therefore, we examined the effects of thiopentone, methohexitone, and propofol on the phagocytosis of viable S. aureus. DESIGN Laboratory study. SETTING University laboratory. PATIENTS Ten healthy volunteers aged 32.5 +/- 7 yrs. INTERVENTIONS Blood sampling. MEASUREMENTS AND MAIN RESULTS Whole blood samples were preincubated with different concentrations of thiopentone, methohexitone, and propofol, which is an isopropylphenol derivate. After viable S. aureus was added, phagocytosis was stopped at different time points. Leukocytes were then stained with monoclonal antibodies for flow cytometric analysis of granulocyte recruitment (ratio of ingesting granulocytes) and phagocytosis activity (fluorescence intensity of ingested bacteria). Both barbiturates inhibited granulocyte recruitment and phagocytosis activity in a dose-dependent manner, whereas propofol did not affect any of the investigated variables. At concentrations higher than 7.6 x 10(-3) M (for thiopentone, p < .008) and 1.1 x 10(-3) M (for methohexitone, p < .04), granulocyte recruitment and phagocytosis activity were significantly inhibited. The calculated inhibitory concentrations (IC50) of thiopentone for granulocyte recruitment and for phagocytosis activity were 1.3 x 10(-2) M and 1.1 x 10(-2) M, respectively. The corresponding values for methohexitone were 3.6 x 10(-3) M and 1.1 x 10(-3) M. CONCLUSIONS Our in vitro model points at substantially different effects of barbiturates and propofol on phagocytosis of S. aureus, which is one of the most important pathogens in patients who need neuroprotective therapy. The inhibitory effects of both barbiturates demonstrate a strong dose-dependency, with more pronounced effects for methohexitone. Impairment of phagocytosis activity was more pronounced than granulocyte recruitment.
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Affiliation(s)
- Annette Ploppa
- Department of Anesthesiology and Intensive Care Medicine, Tübingen University Hospital, Tübingen, Germany
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Fujimoto T, Nishiyama T, Hanaoka K. Inhibitory Effects of Intravenous Anesthetics on Mast Cell Function. Anesth Analg 2005; 101:1054-1059. [PMID: 16192519 DOI: 10.1213/01.ane.0000166955.97368.80] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
UNLABELLED Mast cells play a protective role in the inflammation and auto-tissue injury. The impairment of mast cell function may influence defense against infection. We investigated the effect of four IV anesthetics (thiopental, midazolam, ketamine, and propofol) on the chemotaxis and exocytosis of mast cells. Canine mast cell chemotaxis was measured by the Boyden's blindwell chamber technique using 100 microg/mL of substance P as a stimulator. We measured mast cell exocytosis by measuring released histamine from mast cells using substance P or gamma-monomeric IgG-mediated crosslinking as a stimulator. Thiopental, midazolam, and propofol exerted a dose-dependent inhibitory effect on mast cell chemotaxis. Ketamine, midazolam, and propofol had a dose-dependent inhibitory effect on mast cell exocytosis. In conclusion, midazolam and propofol inhibited both chemotaxis and exocytosis of mast cells, while thiopental only inhibited chemotaxis, and ketamine only inhibited exocytosis. IMPLICATIONS Mast cells play an important role in the antibacterial host-defense mechanism. Thiopental, midazolam, and propofol exerted a dose-dependent inhibitory effect on mast cell chemotaxis. Ketamine, midazolam, and propofol had a dose-dependent inhibitory effect on mast cell exocytosis. The impairment of mast cell function by IV anesthetics may influence the defense against infection.
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Affiliation(s)
- Takahiro Fujimoto
- Department of Anesthesiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Kwak YL. Reduction of Ischemia During Off-Pump Coronary Artery Bypass Graft Surgery. J Cardiothorac Vasc Anesth 2005; 19:667-77. [PMID: 16202908 DOI: 10.1053/j.jvca.2005.04.010] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2005] [Indexed: 12/11/2022]
Affiliation(s)
- Young Lan Kwak
- Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemun-Ku, Seoul, Korea.
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Schneemilch CE, Schilling T, Bank U. Effects of general anaesthesia on inflammation. Best Pract Res Clin Anaesthesiol 2004; 18:493-507. [PMID: 15212341 DOI: 10.1016/j.bpa.2004.01.002] [Citation(s) in RCA: 71] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
General anaesthesia accompanied by surgical stress may influence the inflammatory responses that are essential for maintaining the homeostatic state during the postoperative course. Severe dysregulation of the inflammatory process may provoke or aggravate postoperative complications, e.g. increased susceptibility to infections, inadequate stress reactions and hypercatabolism. Anaesthetics have been suspected of impairing various functions of the immune system either directly, by disturbing the functions of immune-competent cells, or indirectly by modulating the stress response. In the past, conflicting data on the possible immunological side effects of anaesthetics have been published. Potential reasons for these controversial findings include heterogeneous patient study groups with diverse pre-existing diseases, lack of standardisation of surgical procedures, major differences in the length and severity of surgical tissue injury and a small number of randomised studies. Although the immunological effects are of minor consequence in subjects with normal immune functions, the suppression of cellular and humoral immunity following surgery and general anaesthesia may be relevant in patients with pre-existing immune disorders.
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Affiliation(s)
- Christine E Schneemilch
- Department of Anaesthesiology and Intensive Care Medicine, Otto-von-Guericke-University, Leipziger Str. 44 D-39120 Magdeburg, Germany.
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Kato R, Foëx P. Myocardial protection by anesthetic agents against ischemia-reperfusion injury: an update for anesthesiologists. Can J Anaesth 2002; 49:777-91. [PMID: 12374705 DOI: 10.1007/bf03017409] [Citation(s) in RCA: 154] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
PURPOSE The aim of this review of the literature was to evaluate the effectiveness of anesthetics in protecting the heart against myocardial ischemia-reperfusion injury. SOURCE Articles were obtained from the Medline database (1980-, search terms included heart, myocardium, coronary, ischemia, reperfusion injury, infarction, stunning, halothane, enflurane, desflurane, isoflurane, sevoflurane, opioid, morphine, fentanyl, alfentanil sufentanil, pentazocine, buprenorphine, barbiturate, thiopental, ketamine, propofol, preconditioning, neutrophil adhesion, free radical, antioxidant and calcium). PRINCIPAL FINDINGS Protection by volatile anesthetics, morphine and propofol is relatively well investigated. It is generally agreed that these agents reduce the myocardial damage caused by ischemia and reperfusion. Other anesthetics which are often used in clinical practice, such as fentanyl, ketamine, barbiturates and benzodiazepines have been much less studied, and their potential as cardioprotectors is currently unknown. There are some proposed mechanisms for protection by anesthetic agents: ischemic preconditioning-like effect, interference in the neutrophil/platelet-endothelium interaction, blockade of Ca2+ overload to the cytosolic space and antioxidant-like effect. Different anesthetics appear to have different mechanisms by which protection is exerted. Clinical applicability of anesthetic agent-induced protection has yet to be explored. CONCLUSION There is increasing evidence of anesthetic agent-induced protection. At present, isoflurane, sevoflurane and morphine appear to be most promising as preconditioning-inducing agents. After the onset of ischemia, propofol could be selected to reduce ischemia-reperfusion injury. Future clinical application depends on the full elucidation of the underlying mechanisms and on clinical outcome trials.
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Affiliation(s)
- Rie Kato
- Department of Anesthesiology (B1), Graduate School of Medicine, Chiba University, Chiba, Japan.
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The effect of lidocaine on neutrophil respiratory burst during induction of general anaesthesia and tracheal intubation. Eur J Anaesthesiol 2001. [DOI: 10.1097/00003643-200108000-00007] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Nagata T, Kansha M, Irita K, Takahashi S. Propofol inhibits FMLP-stimulated phosphorylation of p42 mitogen-activated protein kinase and chemotaxis in human neutrophils. Br J Anaesth 2001; 86:853-8. [PMID: 11573595 DOI: 10.1093/bja/86.6.853] [Citation(s) in RCA: 39] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Propofol is used in the peri-operative setting and may affect some neutrophil functions. The effects of propofol on the function and intracellular signal transduction systems of neutrophils is controversial. Mitogen-activated protein kinase families (MAPKs) are members of the intracellular signal-transducing systems in eukaryotes. MAPKs have been shown to be involved in neutrophil chemotaxis by the use of PD98059, the specific inhibitor of MAPK/ERK kinase (MEK). The effects of propofol in dimethyl sulfoxide on phosphorylation of MAPKs and chemotaxis were investigated in human neutrophils. Isolated neutrophils (2 x 10(7) cells per ml) from healthy volunteers were incubated with propofol (2-500 microM) and stimulated by N-formyl-L-methionyl-phenylalanine (FMLP) (100 nM). The effects of propofol on the phosphorylation of p44/42 MAPK were investigated by immunoblotting. The effects of FMLP (1 microM) on chemotaxis were investigated with the under-agarose method. The phosphorylation of p42 MAPK and chemotaxis stimulated by FMLP were both inhibited by propofol at clinically relevant concentrations (> or = 10 and > or = 20 microM respectively). PD98059 (50 microM) also inhibited chemotaxis stimulated by FMLP, suggesting the involvement of p42 MAPK in the response. Propofol might therefore inhibit human neutrophil chemotaxis, at least in part, by suppressing the p44/42 MAPK pathway.
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Affiliation(s)
- T Nagata
- Department of Anesthesiology and Critical Care Medicine, Kyushu University, Fukuoka, Japan
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Heine J, Jaeger K, Weingaertner N, Scheinichen D, Marx G, Piepenbrock S. Effects of different preparations of propofol, diazepam, and etomidate on human neutrophils in vitro. Acta Anaesthesiol Scand 2001; 45:213-20. [PMID: 11167168 DOI: 10.1034/j.1399-6576.2001.450213.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
BACKGROUND Intravenous anaesthetics and sedatives can influence polymorphonuclear cell (PMN) functions. Some of the drugs for sedation and anaesthesia have been alternatively dissolved in lipid solutions containing medium (MCT) and/or long chain (LCT) triglycerides. The in vitro effects of two different diazepam (benzyl-alcohol, LCT/MCT), etomidate (propylene-glycol, LCT/MCT), and propofol (LCT, LCT/MCT) preparations on respiratory burst (RB) and phagocytosis of human PMNs were studied. METHODS Diazepam (2, 20 microg ml(-1)), etomidate (0.5, 5 microg ml(-1)), and propofol (6, 60 microg ml(-1)) were investigated in clinical and 10-fold concentrations with flow cytometric assays. The RB was measured with the fluorescent dye rhodamine after induction with Escherichia coli or formyl-methionyl-leucylphenylalanine (FMLP) following priming with tumour necrosis factor alpha (TNF-alpha). Phagocytosis of PMNs was carried out in whole blood after incubation with fluorescein-labelled E. coli. RESULTS LCT-propofol at 60 microg ml(-1) reduced the percentage of PMNs with RB activity after induction with E. coli (52.8+/-20.4) and TNF-alpha/FMLP (10.8+/-5.1)) as well as the percentage of phagocytosing PMNs (48.9+/-19.5) in contrast to LCT/MCT-propofol, which augmented all parameters (85.4+/-10.1, 50.3+/-12.7, 66.5+/-12.5). Also the higher concentrations of LCT/MCT-diluted etomidate and diazepam increased the percentage of RB positive PMNs compared to the alternative compositions. The percentage of phagocytosing PMNs was less reduced with 20 microg ml(-1) LCT/MCT-diazepam (85.2+/-6.9) than with the same concentration of benzyl-alcohol diluted diazepam (68.8+/-12.2) compared to the control. CONCLUSION The in vitro effects of diazepam, etomidate, and propofol are dependent on the solvent applied. The tested LCT/MCT preparations reduce the inhibitory effects on the bacterial killing capacity of PMNs found after incubation with propyleneglycol, benzyl-alcohol, or LCT preparations, respectively.
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Affiliation(s)
- J Heine
- Department of Anaesthesiology, Hannover Medical School, Germany.
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Hofbauer R, Frass M, Salfinger H, Moser D, Hornykewycz S, Gmeiner B, Kapiotis S. Propofol reduces the migration of human leukocytes through endothelial cell monolayers. Crit Care Med 1999; 27:1843-7. [PMID: 10507608 DOI: 10.1097/00003246-199909000-00023] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE To test propofol and the solvent of propofol on leukocyte function in the presence of endothelial cell monolayers. The interactions of leukocytes with endothelial cells play a tremendous role during inflammation. Previous studies have investigated the influence of propofol on leukocytes. DESIGN Prospective, controlled study. SETTING University research laboratories. SUBJECTS Seven independent experiments were performed to investigate the influence of propofol (0.4, 4, and 40 ng/mL) on the migration of human leukocytes through human endothelial cell monolayers. Moreover, the authors tested the solvent of propofol on leukocyte migration. INTERVENTIONS Human endothelial cell monolayers and/or human leukocytes were preincubated with clinically relevant higher and lower concentrations of propofol. The amount of leukocyte migration after 3 hrs was measured with a fluorometer. MEASUREMENTS AND MAIN RESULTS Human endothelial cells isolated from umbilical veins were cultured on microporous membranes until they formed an endothelial cell monolayer. Leukocytes were separated by standard procedures. The migration of leukocytes through monolayers of endothelial cells using the clinically relevant concentration of propofol was reduced to 93% +- 3.8% (so; p < .05) when the leukocytes but not the endothelial cell monolayers were preincubated with propofol. Leukocyte migration was reduced to 80% - 5.9% (p < .05) when only monolayers of endothelial cells were treated with propofol, and was reduced to 73% + 10.4% (p < .05) when both leukocytes and monolayers of endothelial cells were treated with propofol. The higher and lower concentrations showed a dose-dependent effect. The solvent of propofol had no significant effect. CONCLUSION The authors investigated the influence of propofol and its solvent on the interaction between both cell systems-leukocytes and endothelial cells. Propofol is able to reduce significantly the migration of leukocytes through endothelial cell monolayers. The use of different doses revealed a dose-dependent effect. The current model allowed treatment of one cell type: leukocyte or endothelial cell. The results of this investigation indicate that the influence of propofol on leukocyte migration affects endothelial cells more than leukocytes.
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Affiliation(s)
- R Hofbauer
- Department of General Anesthesiology and Intensive Care Medicine, The University of Vienna, Austria
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Hofbauer R, Moser D, Salfinger H, Frass M, Kapiotis S. Sufentanil Inhibits Migration of Human Leukocytes Through Human Endothelial Cell Monolayers. Anesth Analg 1998. [DOI: 10.1213/00000539-199811000-00038] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Hofbauer R, Moser D, Salfinger H, Frass M, Kapiotis S. Sufentanil inhibits migration of human leukocytes through human endothelial cell monolayers. Anesth Analg 1998; 87:1181-5. [PMID: 9806705 DOI: 10.1097/00000539-199811000-00038] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
UNLABELLED The interactions between blood and vascular wall cells are essential for understanding pathophysiological processes, e.g., during inflammation. The influence of anesthetics on leukocyte function is well documented. An inhibitory effect of thiopental, midazolam, and ketamine on leukocyte chemotaxis in a Boyden chamber chemotaxis assay (i.e., endothelial cells were not included) has been demonstrated. Little is known, however, about the influence of sufentanil on the inflammatory processes. To reach their targets in the tissue in vivo, leukocytes must interact with endothelial cell monolayers (ECMs). The aim of the current study was to investigate the influence of sufentanil on the migration of leukocytes through an ECM. Human umbilical vein endothelial cells were cultured to achieve a monolayer. Isolated polymorphonuclear leukocytes and ECM were preincubated with different concentrations of sufentanil. The rate of leukocyte migration against the chemotactic protein formyl-methyl-leucyl-phenylalanine was measured (n = 7). Sufentanil significantly reduced the amount of leukocyte migration through ECM to 77%+/-7.8% (P < 0.05 compared with control). Endothelial cells as well as leukocytes contributed to this effect: treatment of both cell types showed an additive effect. Although lower concentrations showed no effect, high concentrations reduced leukocyte migration through ECM to 61%+/-7.1%. IMPLICATIONS Leukocytes play an important role during inflammation, and anesthetics influence leukocyte functions, e.g., respiratory burst or chemotaxis. The effect of sufentanil on transendothelial leukocyte migration has not been investigated. Therefore, we used a migration assay including endothelial cell monolayers. Sufentanil showed a reducing effect on transendothelial leukocyte migration.
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Affiliation(s)
- R Hofbauer
- Department of General Anesthesiology/Intensive Care Medicine, University of Vienna, Austria.
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Hofbauer R, Moser D, Salfinger H, Frass M, Kapiotis S. Thiopental inhibits migration of human leukocytes through human endothelial cell monolayers in vitro. Intensive Care Med 1998; 24:973-6. [PMID: 9803335 DOI: 10.1007/s001340050698] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
OBJECTIVES The interactions between blood and vascular wall cells are essential for the understanding of pathophysiologic processes, e.g. inflammation. The influence of the anesthetic drug thiopental on leukocyte function is well documented. Recently, an inhibitory effect of thiopental on leukocyte chemotaxis in a Boyden chamber assay (i.e. endothelial cells were not included) was demonstrated. In vivo, leukocytes have to interact with endothelial cell monolayers to invade the tissue. The influence of thiopental on a monolayer of endothelial cells has not yet been investigated. The aim of the current study was to investigate the influence of thiopental on the migration of leukocytes through endothelial cell monolayers (ECM). MATERIAL AND METHODS Human umbilical vein endothelial cells (HUVEC) were isolated and cultured on microporous membrane filters to achieve a monolayer. Isolated polymorphonuclear leukocytes (PMNL) as well as ECM were preincubated with different concentrations of thiopental. The rate of leukocyte migration against the chemotactic protein formyl-methyl-leucyl-phenylalanine was measured (n = 7). Thiopental was able to reduce the amount of leukocyte migration through ECM significantly. CONCLUSION In conclusion, we could show that thiopental is able to reduce the migration of PMNL through ECM significantly.
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Affiliation(s)
- R Hofbauer
- Department of Anesthesiology and Intensive Care Medicine, University of Vienna, Austria.
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Hofbauer R, Moser D, Hammerschmidt V, Kapiotis S, Frass M. Ketamine significantly reduces the migration of leukocytes through endothelial cell monolayers. Crit Care Med 1998; 26:1545-9. [PMID: 9751591 DOI: 10.1097/00003246-199809000-00022] [Citation(s) in RCA: 23] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To study the role of neutrophils in host defense, using human endothelial cells in migration studies in the presence of ketamine (0.3, 3, and 30 microg/mL). DESIGN Prospective, controlled study. SETTING University research laboratories. SUBJECTS Seven independent experiments from different donors were done, investigating the influence of ketamine (0.3, 3, and 30 microg/mL) to the migration of human leukocytes through human endothelial cell monolayers. INTERVENTIONS Human endothelial cell monolayers and/or human leukocytes were preincubated with clinically relevant (3 microg/mL), higher (30 microg/mL), and lower (0.3 microg/mL) concentrations of ketamine. The amount of leukocyte migration after 3 hrs was measured in a fluorometer. MEASUREMENTS AND MAIN RESULTS Human endothelial cells isolated from umbilical veins were cultured on microporous membranes (polyethylene-terephthalat membranes) until they formed an endothelial cell monolayer. Leukocytes were separated by standard procedures. The migration of leukocytes through monolayers of endothelial cells under the clinically relevant concentration of ketamine was reduced to 59+/-9.8% (SD) (p< .05) when leukocytes but not the endothelial cell monolayers were preincubated with ketamine. Leukocyte migration was reduced to 92+/-7.3% (p > .05) when only monolayers of endothelial cells were treated with ketamine, and to 52+/-8.8% (p< .05) when both leukocytes and monolayers of endothelial cells were treated with ketamine. The higher and lower concentrations showed a dose-dependent effect. CONCLUSIONS We investigated the cellular interaction between both cell systems, leukocytes and endothelial cells, simultaneously in the presence of ketamine. Ketamine is able to reduce significantly the migration of leukocytes through endothelial cell monolayers. The use of different dosages revealed a dose-dependent effect. The current model allowed treatment of one cell type, either leukocyte or endothelial cell. Ketamine inhibits the function of leukocytes more than the function of endothelial cells.
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Affiliation(s)
- R Hofbauer
- Department of General Anesthesiology and Intensive Care, Clinical Institute of Medical and Chemical Laboratory Diagnostics, School of Medicine, The University of Vienna, Austria.
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Heller A, Heller S, Blecken S, Urbaschek R, Koch T. Effects of intravenous anesthetics on bacterial elimination in human blood in vitro. Acta Anaesthesiol Scand 1998; 42:518-26. [PMID: 9605366 DOI: 10.1111/j.1399-6576.1998.tb05160.x] [Citation(s) in RCA: 47] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Since anesthetics are widely used in critically ill patients, this study investigates anesthetic effects on neutrophil and monocyte function concerning bacterial elimination in human whole blood. METHODS The effects of thiopental (20 and 200 microg/ml), propofol (5 and 50 microg/ml), midazolam (0.15 and 1.5 microg/ml) and ketamine (3 and 30 microg/ml) on elimination of Escherichia (E.) coli from whole blood were investigated in vitro after incubation for 1 h in both clinical (1) (n=10) and 10-fold higher (h) (n=11) concentrations. These data were compared to neutrophil and monocyte phagocytosis (1; n=6) and burst activity (1; n=10, h; n=11), measured by flow cytometry. To enable quantification of the clearance process, a defined number of 10(5) colony forming units of E. coli were added to the blood assays and bacterial growth was determined. RESULTS All anesthetics delayed bacterial clearance from the blood in the 10-fold concentration (P<0.05). Thiopental (1+h) and propofol (h) suppressed neutrophil (59+/-3% and 38+/-6%) and monocytic (45+/-6% and 30+/-11%) oxidative burst (P<0.01). Phagocytosis was reduced even after propofol (1) in polymorphonuclear leukocytes (PMN) (34+/-9%; P<0.05) and monocytes (35+/-11%). Ketamine (h) prolonged bacterial elimination (P<0.01), which did correlate with inhibition of monocytic phagocytosis, by 26+/-14%. Midazolam application (h) resulted in an inhibition of PMN-respiratory burst by 19+/-6% (P<0.05) and impaired bacterial clearance (P<0.05). CONCLUSION Thiopental, propofol, midazolam and ketamine affect E. coli clearance and neutrophil and monocyte oxidative burst and phagocytosis in vitro only in high concentrations, while thiopental inhibited monocytic burst and propofol impaired PMN phagocytosis even in clinically used concentrations. These data suggest that i.v. anesthetics in concentrations recommended for general anesthesia seem to have minor influence on the investigated host defense mechanisms.
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Affiliation(s)
- A Heller
- Department of Anesthesiology and Operative Intensive Care Medicine, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Germany
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Nishina K, Akamatsu H, Mikawa K, Shiga M, Maekawa N, Obara H, Niwa Y. The Inhibitory Effects of Thiopental, Midazolam, and Ketamine on Human Neutrophil Functions. Anesth Analg 1998. [DOI: 10.1213/00000539-199801000-00032] [Citation(s) in RCA: 63] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Nishina K, Akamatsu H, Mikawa K, Shiga M, Maekawa N, Obara H, Niwa Y. The inhibitory effects of thiopental, midazolam, and ketamine on human neutrophil functions. Anesth Analg 1998; 86:159-65. [PMID: 9428872 DOI: 10.1097/00000539-199801000-00032] [Citation(s) in RCA: 43] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
UNLABELLED We investigated the effect of thiopental, midazolam, and ketamine (at clinically relevant concentrations and at 0.1 and 10 times these concentrations) on several aspects of human neutrophil functions. The three intravenous (i.v.) anesthetics significantly decreased chemotaxis, phagocytosis, and reactive oxygen species (ROS) (O2-, H2O2, OH) production of neutrophils in a dose-dependent manner. At clinically relevant concentrations, thiopental and midazolam significantly depressed these neutrophil functions. However, ketamine at the clinical plasma concentration did not impair chemotaxis or ROS production, except phagocytosis. In contrast, the three anesthetics had no effect on the levels of ROS production by a cell-free ROS generating system. In addition, intracellular calcium concentrations in neutrophils stimulated by N-formyl-L-methionyl-L-leucil-L-phenylalanine were dose-dependently decreased in the presence of each of the three anesthetics. The suppression of an increase in intracellular calcium concentrations may be responsible for the inhibition of neutrophil functions by the i.v. anesthetics. IMPLICATIONS Neutrophils play an important role in the antibacterial host defense system and autotissue injury. We found that thiopental and midazolam (but not ketamine), at clinically relevant concentrations, impaired the neutrophil functions.
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Affiliation(s)
- K Nishina
- Department of Anaesthesiology, Kobe University School of Medicine, Japan
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Mathy-Hartert M, Deby-Dupont G, Hans P, Deby C, Lamy M. Protective activity of propofol, Diprivan and intralipid against active oxygen species. Mediators Inflamm 1998; 7:327-33. [PMID: 9883967 PMCID: PMC1781863 DOI: 10.1080/09629359890848] [Citation(s) in RCA: 52] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
We separately studied the antioxidant properties of propofol (PPF), Diprivan (the commercial form of PPF) and intralipid (IL) (the vehicle solution of PPF in Diprivan) on active oxygen species produced by phorbol myristate acetate (10(-6) M)-stimulated human polymorphonuclear leukocytes (PMN: 5 x 10(5) cells/assay), human endothelial cells (5 x 10(5) cells/assay) or cell-free systems (NaOCl or H2O2/peroxidase systems), using luminol (10(-4) M)-enhanced chemiluminescence (CL). We also studied the protective effects of Diprivan on endothelial cells submitted to an oxidant stress induced by H2O2/MPO system: cytotoxicity was assessed by the release of preincorporated 51Cr. Propofol inhibited the CL produced by stimulated PMN in a dose dependent manner (until 5 x 10(-5) M, a clinically relevant concentration), while Diprivan and IL were not dose-dependent inhibitors. The CL produced by endothelial cells was dose-dependently inhibited by Diprivan and PPF, and weakly by IL (not dose-dependent). In cell free systems, dose-dependent inhibitions were obtained for the three products with a lower effect for IL. Diprivan efficaciously protected endothelial cells submitted to an oxidant stress, while IL was ineffective. By HPLC, we demonstrated that PPF was not incorporated into the cells. The drug thus acted by scavenging the active oxygen species released in the extracellular medium. IL acted in the same manner, but was a less powerful antioxidant.
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Affiliation(s)
- M Mathy-Hartert
- Centre for the Biochemistry of Oxygen, Institut de Chimie, Domaine Universitaire du Sart Tilman, Liège, Belgium
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