22 8 K CC SURFACTANT THERAPY FOR MECONIUM ASPIRATION SYNDROME

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22 8 K  CC  SURFACTANT THERAPY FOR MECONIUM ASPIRATION SYNDROME

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Int. J. Med. Sci. 2011, 8 http://www.medsci.org 501 IInntteerrnnaattiioonnaall JJoouurrnnaall ooff MMeeddiiccaall SScciieenncceess 2011; 8(6):501-509 Research Paper Oral Rehydration Therapy for Preoperative Fluid and Electrolyte Man-agement Hideki Taniguchi1,2,, Toshio Sasaki2, Hisae Fujita2 1. School of Nutrition & Dietetics, Kanagawa University of Human Services, Yokosuka, Kanagawa 238-8522, Japan 2. Department of Anesthesiology, Kanagawa Cancer Center, Yokohama 241-0815, Japan  Corresponding author: Hideki Taniguchi, MD, School of Nutrition & Dietetics, Kanagawa University of Human Services, 1-10-1 Heiseicho, Yokosuka, Kanagawa 238-8522, Japan. Address e-mail: taniguchi-hdk@kuhs.ac.jp © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/ licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. Received: 2011.06.26; Accepted: 2011.08.19; Published: 2011.08.25 Abstract Aim: Preoperative fluid and electrolyte management is usually performed by intravenous therapy. We investigated the safety and effectiveness of oral rehydration therapy (ORT) for preoperative fluid and electrolyte management of surgical patients. Methods: The study consisted of two studies, designed as a prospective observational study. In a pilot study, 20 surgical patients consumed 1000 mL of an oral rehydration solution (ORS) until 2 h before induction of general anesthesia. Parameters such as serum electrolyte con-centrations, fractional excretion of sodium (FENa) as an index of renal blood flow, volume of esophageal-pharyngeal fluid and gastric fluid (EPGF), and patient satisfaction with ORT were assessed. In a follow-up study to assess the safety of ORT, 1078 surgical patients, who con-sumed ORS until 2 h before induction of general anesthesia, were assessed. Results: In the pilot study, water, electrolytes, and carbohydrate were effectively and safely supplied by ORT. The FENa value was increased at 2 h following ORT. The volume of EPGF collected following the induction of anesthesia was 5.3±5.6 mL. In the follow-up study, a small amount of vomiting occurred in one patient, and no aspiration occurred in the patients. Conclusion: These results suggest that ORT is a safe and effective therapy for the pre-operative fluid and electrolyte management of selected surgical patients. Key words: Oral rehydration therapy, preoperative fluid and electrolytes, oral rehydration solution Introduction Preoperative fasting beginning the day before surgery has been standard practice to prevent aspira-tion pneumonia associated with general anesthesia [1]; thus before surgery, the patients are inevitably exposed to dry month and hunger. In Japan, pre-operative fluid and electrolyte management is usually performed by intravenous therapy, and the fasting time prior to surgery seems to be longer than in other countries [2]. However, due to a lack of sufficient scientific evidence [1], the period of preoperative fasting has recently been reevaluated, and societies of anesthesiology in the United States and most Euro-pean countries have revised the practice guidelines for preoperative fasting so that the oral intake of clear fluids may be permissible up to 23 h before surgery in selected surgical patients (excluding those in whom delayed gastric emptying is suspected) [3]. In addi-tion, an approach for minimizing THE EFFICACY OF SURFACTANT THERAPY FOR MECONIUM ASPIRATION SYNDROME (MAS) Dr VO HOAI THUONG EMERGENCY DEPARTMENT MAS What is the role of surfactant in the treatment of MECONIUM ASPIRATION SYNDROME ? META- ANALYSIS META-ANALYSIS META-ANALYSIS RCTs, 326 infants  trials: no difference of mortality  trials (n = 208) : The risk of requiring ECMO was significantly reduced; (RR:0.64, 95% CI 0.46, 0.91); NNT (95% CI 3, 25)  trial (n = 40): a statistically significant reduction in the length of hospital stay [mean difference - days (95% CI -14, -3 days)]  No statistically significant reductions in any other outcomes studied META-ANALYSIS Conclusion:  Reduce the severity of respiratory illness, and the number of infants requiring support with ECMO  The efficacy of surfactant therapy compared to, or in conjunction with, other treatment: iNO, surfactant lavage and HFV remains to be tested META-ANALYSIS META-ANALYSIS RCTs, 512 MAS neonates (257 cases PS/255 cases in the control group)      Reduced OI(P=0.003) Shortened hospitalization days (P=0.0001) Decreased mortality rate (OR=0.47; 95%CI: 0.24, 0.93; P=0.03) significantly Increased arterial oxygen/alveolar oxygen ratio (P0.5) and  High mean airway pressure (>10 to 12 cmH2O)  UP TODATE The management of MAS is supportive The following approach is suggested (Grade 2C): • Maintenance of adequate oxygenation and ventilation • Mild or moderate disease: Supplemental oxygen therapy is usually adequate • Severe disease: mechanical ventilation, surfactant therapy, and/or iNO • Have failed to response to other interventions, ECMO may be a life-saving intervention CONCLUSION  Surfactant therapy is efficacious for severe MAS Decrease mortality rate  Shorten hospitalization days  Reduce the severity of respiratory illness   Further evidence from RCTs is needed to prove the efficacy THANKS FOR YOUR ATTENTION Int. J. Med. Sci. 2010, 7 http://www.medsci.org 72IInntteerrnnaattiioonnaall JJoouurrnnaall ooff MMeeddiiccaall SScciieenncceess 2010; 7(2):72-81 © Ivyspring International Publisher. All rights reserved Research Paper WT1 PEPTIDE VACCINATION IN COMBINATION WITH IMATINIB THERAPY FOR A PATIENT WITH CML IN THE CHRONIC PHASE Miwako Narita1 , Masayoshi Masuko2, Tohri Kurasaki3, Toshiki Kitajima3, Shoko Takenouchi3, Anri Sai-toh1, Norihiro Watanabe1, Tatsuo Furukawa2, Ken Toba3, Ichiro Fuse4, Yoshifusa Aizawa3, Manabu Kawa-kami5, Yoshihiro Oka6, Haruo Sugiyama6 and Masuhiro Takahashi1 1. Laboratory of Hematology and Oncology, Graduate School of Health Sciences, Niigata University, Niigata, Japan 2. Division of Stem Cell Transplantation, Niigata University Medical and Dental General Hospital, Niigata, Japan 3. Division of Hematology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan 4. Division of Bioscience Medical Research Center, Niigata University Medical and Dental General Hospital, Niigata, Japan 5. Department of Medicine, National Hospital Organization, Osaka Minami Medical Center, Osaka, Japan 6. Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan  Corresponding author: Miwako Narita M.D., Laboratory of Hematology and Oncology, Graduate School of Health Sciences, Niigata University, 2-746, Asahimachi-dori, Chuo-ku, Niigata, 951-8518 Japan. (Telephone/fax) 81-25227-0836, (email) naritami@clg.niigata-u.ac.jp Received: 2009.11.07; Accepted: 2010.04.09; Published: 2010.04.20 Abstract Although tyrosine kinase inhibitors is effective for dramatically reducing CML cells, it might be difficult to eradicate completely the CML stem cells. We aimed to clarify the safety and effects of WT1 peptide vaccination in combination with imatinib therapy for a CML patient. A 51 year-old male with CML in CP, who showed a resistance against imatinib therapy for 2.5 years, began to be treated with 9mer modified-type WT1 peptides in combination with standard dose of imatinib. Although every 2-week-administration of WT1 peptides for 22 weeks did not show definite effects on the quantification of bcr-abl transcripts, by changing the admin-istration from every 2 weeks to 4 weeks bcr-abl transcripts decreased remarkably. After 11 months of every 4-week-administration of the peptides and 12 months post cessation of the peptides bcr-abl transcripts achieved to the level below detection by RQ/RT-PCR (complete molecular response). WT1/MHC tetramer+CD8+ CTLs, which appeared after the second administration of WT1 peptides and remained more than 15 in number among 106 CD8+ T cells throughout the administration of WT1 peptides, are still present in the blood on 14th month post cessation of the peptides. An in vitro study as to the cytotoxicity of lymphocytes induced by mixed lymphocyte peptide culture demonstrated that cultured lymphocytes possessed cytotoxicity against WT1 expressing leukemia cells and the cytotoxicity was WT1-specific and MHC class I restricted. The present study showed that WT1 peptide vaccination in combination with TKI is feasible and effective in the therapy for imati-nib-resistant CML. Key words: WT1 peptide vaccination, CML, imatinib, bcr-abl transcripts, WT1 tetramer, cytotoxic-ity INTRODUCTION While tyrosine kinase inhibitors (TKIs) such as imatinib are currently regarded as Saline lavage with substitution of bovine surfactant in term neonates with meconium aspiration syndrome (MAS) transferred for extracorporeal membrane oxygenation (ECMO): a pilot study Jens C Möller, Martina Kohl, Irwin Reiss*, Wiebke Diederich, Esther M Nitsche, Wolfgang Göpel and Ludwig Gortner* Background: Meconium aspiration syndrome (MAS) is still a condition associated with a high mortality, and many patients require extracorporeal membrane oxygenation (ECMO) as rescue therapy. Beneficial effects of surfactant and perflubron lavage have been reported. However, pure surfactant supplementation has not been proven to be beneficial in the most severe forms of MAS. This study was performed to demonstrate an improvement in oxygenation in neonates transferred for ECMO and fulfilling ECMO criteria with a saline lavage and surfactant resupplementation. Methods: Twelve newborns with MAS [gestational age 36–40 weeks, mean birth weight 3200g, age 4–16h, oxygenation index (OI) >40] transferred for ECMO therapy were treated with saline lavage (5–10cm 3 /kg body weight, as long as green colored retrieval was observed) and resupplementation with bovine surfactant (Alveofact, Boehringer, Ingelheim, Germany). The OI at admission and 3h after this procedure was compared using the t-test for paired samples. ECMO was available as rescue therapy at all times. Results: The OI decreased from 49.4 (SD±13.3) to 27.4 (SD±7.3), P<0.01. The decrease was sustained in nine patients, three patients required ECMO and all patients survived. Conclusions: As MAS is a condition with parenchymal damage, pulmonary hypertension and obstructive airway disease, no simple causative therapy is possible. Surfactant application after removal of meconium by extensive lavage is feasible as long as 16h after birth even in infants considered for ECMO therapy; it might reduce the necessity of ECMO. Addresses: Klinik für Pädiatrie der Medizinischen Universität Lübeck, Lübeck, Germany. *Justus- Liebig-University Children’s Hospital, Gießen, Germany. Correspondence: Prof. Dr. Jens Möller, Klinik für Pädiatrie der Medizinischen Universität Lübeck, Kahlhorststr. 31-35, D- 23538 Lübeck, Germany. Tel and Fax: +49 451 5002555; e-mail: Dmoeller@t-online.de Presented in parts at the 11th Congress of the European Society of Intensive Care Medicine, Paris, 1997. Keywords: bronchoalveolar lavage, meconium aspiration, neonates, respiratory failure, surfactant Received: 6 January 1998 Revisions requested: 11 June 1998 Revisions received: 31 July 1998 Accepted: 12 February 1999 Published: 15 March 1999 Crit Care 1999, 3:19–22 The original version of this paper is the electronic version which can be seen on the Internet (http://ccforum.com). The electronic version may contain additional information to that appearing in the paper version. © Current Science Ltd ISSN 1364-8535 Research paper 19 Introduction Meconium aspiration syndrome (MAS) is a leading cause of severe respiratory failure in term neonates and is associ- ated with high mortality. Extracorporeal membrane oxy- genation (ECMO) has improved the outcome of infants with MAS significantly [1]. In addition, the enforcement of standardized management algorithms, with detailed advice for pharyngeal and in some cases tracheal suction- ing, have reduced the incidence of MAS, especially in Europe [2–7]. In our state, only four cases in 29000 deliveries were reg- istered in 1997 [8]. In cases of MAS with moderate sever- ity, exogenous surfactant therapy improves oxygenation and increases the rate of survival [9]. Infants are still transferred, however, to ECMO centers after prolonged periods of hypoxemia; in extreme condi- tions, with oxygenation indices >40, the transport-associ- ated mortality is high [10]. Treatment options that improve the conditions in severe MAS and can be used in all NICU are therefore warranted. As MAS is a condition combining pulmonary hypertension and obstructive airway disease with a considerable Open Access Available online http://ccforum.com/content/11/3/R66 Page 1 of 10 (page number not for citation purposes) Vol 11 No 3 Research Surfactant therapy for acute respiratory failure in children: a systematic review and meta-analysis Mark Duffett 1 , Karen Choong 1 , Vivian Ng 2 , Adrienne Randolph 3 and Deborah J Cook 4 1 Department of Critical Care, McMaster Children's Hospital, 1200 Main St. W., Hamilton, Ontario L8S 4J9, Canada 2 Grand River Hospital, 835 King St. West, Kitchener, Ontario N2G 1G3, Canada 3 Children's Hospital Boston, 300 Longwood Avenue, MSICU, FA-108, Boston, MA 02115, USA 4 Department of Clinical Epidemiology and Statistics, McMaster University, 1200 Main St. W., Hamilton, Ontario L8N 3Z5, Canada Corresponding author: Mark Duffett, duffett@hhsc.ca Received: 16 Mar 2007 Revisions requested: 13 Apr 2007 Revisions received: 11 May 2007 Accepted: 15 Jun 2007 Published: 15 Jun 2007 Critical Care 2007, 11:R66 (doi:10.1186/cc5944) This article is online at: http://ccforum.com/content/11/3/R66 © 2007 Duffett et al., licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Introduction Exogenous surfactant is used to treat acute respiratory failure in children, although the benefits and harms in this setting are not clear. The objective of the present systematic review is to assess the effect of exogenous pulmonary surfactant on all-cause mortality in children mechanically ventilated for acute respiratory failure. Methods We searched the MEDLINE, EMBASE, CINAHL and Ovid Healthstar databases, the bibliographies of included trials and review articles, conference proceedings and trial registries. We included prospective, randomized, controlled trials of pulmonary surfactant that enrolled intubated and mechanically ventilated children with acute respiratory failure. We excluded trials that exclusively enrolled neonates or patients with asthma. Two reviewers independently rated trials for inclusion, extracted data and assessed the methodologic quality. We quantitatively pooled the results of trials, where suitable, using a random effects model. Results Six trials randomizing 314 patients were included. Surfactant use reduced mortality (relative risk = 0.7, 95% confidence interval = 0.4 to 0.97, P = 0.04), was associated with increased ventilator-free days (weighted mean difference = 2.5 days, 95% confidence interval = 0.3 to 4.6 days, P = 0.02) and reduced the duration of ventilation (weighted mean difference = 2.3 days, 95% confidence interval = 0.1 to 4.4 days, P = 0.04). Conclusion Surfactant use decreased mortality, was associated with more ventilator-free days and reduced the duration of ventilation. No serious adverse events were reported. Introduction Acute respiratory failure remains the primary indication for admission to North American paediatric intensive care units (PICUs) and accounts for significant mortality, morbidity and resource utilization [1]. Respiratory infections, in particular pneumonia and severe bronchiolitis, are the most common causes of respiratory failure requiring mechanical ventilation in children [1]. Alterations in endogenous surfactant play a role in the patho- genesis of many causes of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) [2]. Surfactant dysfunc- tion, destruction and inactivation have also been demon- strated in children with acute respiratory insufficiency due to bronchiolitis [3,4]. The administration of exogenous surfactant may reduce the need for mechanical ventilation and its associ- ated sequelae by restoring surfactant levels and function. Inspired by the success of surfactants in reducing mortality and the need for mechanical ventilation in neonatal respiratory distress BS Nguyễn Phạm Minh Trí Khoa Hồi Sức Sơ Sinh Description of the condition  newborn inhales mixture of meconium and amniotic fluid into lungs in delivery Meconium Aspiration: The Statistics  Infants with MEC aspiration syndrome 35% need mechanical ventilation (range 25-60%) 12% die (range 5-37%) Management: at present         Assisted ventilation Sedation Surfactant Nitric oxide ECMO Circulatory support Antibiotics ……  Largely SUPPORTIVE Remove MEC from the lung: Why NOT ??? Lung lavage for meconium aspiration syndrome in newborn infants (Review) Hahn S, Choi HJ, Soll R, Dargaville PA Cochrane Database of Systematic Reviews 2013 Issue Art No.: CD003486 Objectives  Evaluate Effects of LUNG LAVAGE on Morbidity and Mortality in newborn infants with MAS Search methods  Search database:     Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE, and EMBASE up to December 2012 previous reviews including cross-references, abstracts, conference proceedings; and expert informants Search words:  meconium aspiration, pulmonary surfactants, bronchoalveolar lavage, lung lavage, pulmonary lavage Selection criteria   Randomised controlled trials that evaluated the effects of lung lavage in infants with MAS Lung lavage: intervention in which fluid is instilled into the lung and then removed by suctioning and/or postural drainage   Fluids that have been used for this purpose include saline, full-strength and dilute surfactant, and perfluorocarbon Standard care: no lavage therapy, but include routine suction of the endotracheal tube to maintain its patency Outcome 1: Death Outcome 2: Use of ECMO Outcome 3: Death or use of ECMO Outcome 4: Pneumothorax Outcome 5: Oxygenation index Outcome 6: AaDO2 Outcome 7: PaO2/FiO2 Result Analysis  Lung lavage has effect in all outcomes, but only these are significant in statistics:   Outcome 3: Death or Use of ECMO Outcome 5: Oxygenation index at 48 hours Comparison LUNG LAVAGE FOLLOWED BY SURFACTANT BOLUS VERSUS SURFACTANT BOLUS Lung lavage followed by surfactant bolus vs surfactant bolus   One study: Gadzinowski 2008 Outcomes:   Death Pneumothorax Outcome 1: Death Outcome 2: Pneumothorax Authour’s conclusion  In infants with MAS, lung lavage with diluted surfactant may be beneficial (Grade 2B)   A Grade recommendation is a weak recommendation It means "this is our suggestion, but you may want to think about it” For Grade recommendations, benefits and risks may be finely balanced, or uncertain Grade B evidence is evidence from randomized trials with important limitations, or very strong evidence of some other form Authour’s conclusion  Additional controlled clinical trials of lavage therapy should be conducted to     confirm the treatment effect refine the method of lavage treatment compare lavage treatment with other approaches, including surfactant bolus therapy Long-term outcomes should be evaluated in further clinical trials [...]... the non lavaged control group were not reported and are not now obtainable Three studies are included in this review  Wiswell 2002; Gadzinowski 2008; Dargaville 2011 Study analysis  Type of lavage fluid •  Lavage aliquot volume • •  All included studies used diluted surfactant for lavage  5 mL/kg in all studies comparing surfactant lavage with standard care  5 mL/kg in the study comparing surfactant... comparing surfactant lavage followed by bolus surfactant with surfactant bolus therapy Timing of lavage • mean age  than six hours in all included studies Comparison 1 LUNG LAVAGE VERSUS STANDARD CARE Lung lavage vs Standard care   Two studies: Dargaville 2011; Wiswell 2002 Outcomes:      Death Use of ECMO Death or Use of ECMO Pneumothorax Indices of pulmonary function: Oxygenation Index, AaDO2 and... Oxygenation index Outcome 6: AaDO2 Outcome 7: PaO2/FiO2 Result Analysis  Lung lavage has effect in all outcomes, but only these are significant in ... of surfactant in the treatment of MECONIUM ASPIRATION SYNDROME ? META- ANALYSIS META-ANALYSIS META-ANALYSIS RCTs, 326 infants  trials: no difference of mortality  trials (n = 2 08) : The risk... oxygen therapy, the incidences of air leak, pulmonary hemorrhage and ICH META-ANALYSIS Conclusion:  Currently published evidence from RCTs suggests that PS replacement therapy is effective for. .. of infants requiring support with ECMO  The efficacy of surfactant therapy compared to, or in conjunction with, other treatment: iNO, surfactant lavage and HFV remains to be tested META-ANALYSIS

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