ABSTRACT
INTRODUCTION: In metabolic surgery, hemorrhage is the most common major complication. This study investigated whether peroperative administration of tranexamic acid (TXA) reduced the risk of hemorrhage in patients undergoing laparoscopic sleeve gastrectomy (SG). METHODS: In this double-blind randomized controlled trial, patients undergoing primary SG in a high-volume bariatric hospital were randomized (1:1) to receive 1500-mg TXA or placebo peroperatively. Primary outcome measure was peroperative staple line reinforcement using hemostatic clips. Secondary outcome measures were peroperative fibrin sealant use and blood loss, postoperative hemoglobin, heart rate, pain, major and minor complications, length of hospital stay (LOS), side effects of TXA (i.e., venous thrombotic event (VTE)) and mortality. RESULTS: In total, 101 patients were analyzed and received TXA (n = 49) or placebo (n = 52). There was no statistically significant difference in hemostatic clip devices used in both groups (69% versus 83%, p = 0.161). TXA administration showed significant positive changes in hemoglobin levels (millimoles per Liter; 0.55 versus 0.80, p = 0.013), in heart rate (beats per minute; -4.6 versus 2.5; p = 0.013), in minor complications (Clavien-Dindo ≤ 2, 2.0% versus 17.3%, p = 0.016), and in mean LOS (hours; 30.8 versus 36.7, p = 0.013). One patient in the placebo-group underwent radiological intervention for postoperative hemorrhage. No VTE or mortality was reported. CONCLUSION: This study did not demonstrate a statistically significant difference in use of hemostatic clip devices and major complications after peroperative administration of TXA. However, TXA seems to have positive effects on clinical parameters, minor complications, and LOS in patients undergoing SG, without increasing the risk of VTE. Larger studies are needed to investigate the effect of TXA on postoperative major complications.
Subject(s)
Antifibrinolytic Agents , Tranexamic Acid , Humans , Tranexamic Acid/therapeutic use , Tranexamic Acid/adverse effects , Antifibrinolytic Agents/therapeutic use , Antifibrinolytic Agents/adverse effects , Postoperative Hemorrhage/prevention & control , Postoperative Hemorrhage/chemically induced , Double-Blind Method , Blood Loss, Surgical/prevention & control , Administration, IntravenousABSTRACT
INTRODUCTION: Morbid obesity is an important risk factor for developing a venous thromboembolic events (VTE) after surgery. Fast-track protocols in metabolic surgery can lower the risk of VTE in the postoperative period by reducing the immobilization period. Administration of thromboprophylaxis can be a burden for patients. This study aims to compare extended to restricted thromboprophylaxis with low molecular weight heparin (LMWH) for patients undergoing metabolic surgery. METHODS: In this single center retrospective cohort study, data was collected from patients undergoing a primary Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) between 2014 and 2018. Patients operated in 2014-2017 received thromboprophylaxis for two weeks. In 2018, patients only received thromboprophylaxis during hospital admission. Patients already using anticoagulants were analyzed as a separate subgroup. The primary outcome measure was the rate of clinically significant VTEs within three months. Secondary outcome measures were postoperative hemorrhage and reoperations for hemorrhage. RESULTS: 3666 Patients underwent a primary RYGB or SG following the fast-track protocol. In total, two patients in the 2014-2017 cohort were diagnosed with VTE versus zero patients in the 2018 cohort. In the historic group, 34/2599 (1.3%) hemorrhages occurred and in the recent cohort 8/720 (1.1%). Postoperative hemorrhage rates did not differ between the two cohorts (multivariable analysis, p = 0.475). In the subgroup of patients using anticoagulants, 21/347(6.1%) patients developed a postoperative hemorrhage. Anticoagulant use was a significant predictor of postoperative hemorrhage (p < 0.001). CONCLUSION: Despite the restricted use of thromboprophylaxis administration since 2018, the rate of VTEs did not increase. This may be explained by quick mobilization and hospital discharge, as encouraged by the fast-track protocol. There was no significant difference in postoperative hemorrhage rates by thromboprophylaxis protocol. Short term use of thromboprophylaxis in metabolic surgery is safe in patients at low risk of VTE.
Subject(s)
Bariatric Surgery , Chemoprevention/methods , Heparin, Low-Molecular-Weight/administration & dosage , Obesity, Morbid/surgery , Postoperative Complications/prevention & control , Venous Thromboembolism/prevention & control , Adult , Age Factors , Aged , Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Bariatric Surgery/adverse effects , Chemoprevention/adverse effects , Cohort Studies , Comorbidity , Drug Administration Schedule , Female , Heparin, Low-Molecular-Weight/adverse effects , Humans , Male , Middle Aged , Obesity, Morbid/epidemiology , Postoperative Complications/epidemiology , Postoperative Hemorrhage/epidemiology , Postoperative Hemorrhage/etiology , Preoperative Care/adverse effects , Preoperative Care/methods , Retrospective Studies , Venous Thromboembolism/epidemiology , Venous Thrombosis/epidemiology , Venous Thrombosis/prevention & controlABSTRACT
BACKGROUND: Early recovery of patients following sedation/analgesia and anesthesia is important in ambulatory practice. The aim of this study was to assess whether modafinil, used for the treatment of narcolepsy, improves recovery following sedation/analgesia. METHODS: Patients scheduled for extracorporeal shock wave lithotripsy were randomly assigned to one of four groups. Two groups received a combination of fentanyl/midazolam with either modafinil or placebo. The remaining groups received remifentanil/propofol with either modafinil or placebo. Modafinil 200 mg was administered to the treatment group patients 1 h before sedation/analgesia. Groups were compared using the digital symbol substitution test (DSST), trail making test (TMT), observer scale of sedation and analgesia (OAA/S) and Aldrete score. Verbal rating scale (VRS) scores for secondary outcome variables e.g. energy, tiredness and dizziness were also recorded before and after treatment. RESULTS: Sixty-seven patients successfully completed the study. Groups received similar doses of sedation and analgesic drugs. No statistically significant difference was found for DSST between groups. No significant adverse effects occurred in relation to modafinil. No statistically significant difference between groups was identified for TMT, OAA/S and Aldrete scores. The mean VRS score for tiredness was lesser in the modafinil/fentanyl/midazolam group [1.3 (2.0)] compared with the placebo group [3.8 (2.5)], P=0.02. Such a difference was not found between the remifentanil/propofol groups [placebo 2.6 (2.2) vs. modafinil 3.1(2.7)], p>0.05. Dizziness was greater in the modafinil/remifentanil/propofol group 1.7 (2.0) vs. placebo 0.0 (0.5), p<0.05. CONCLUSION: Modafinil reduces patient-reported tiredness after sedation/analgesia but does not improve recovery in terms of objective measures of patient psychomotor skills.
Subject(s)
Benzhydryl Compounds/therapeutic use , Central Nervous System Stimulants/therapeutic use , Fatigue/prevention & control , Psychomotor Performance/drug effects , Adolescent , Adult , Aged , Aged, 80 and over , Analgesia , Anesthesia Recovery Period , Anesthetics, Inhalation/administration & dosage , Appetite/drug effects , Deep Sedation , Dizziness/prevention & control , Fentanyl/administration & dosage , Humans , Lithotripsy , Midazolam/administration & dosage , Middle Aged , Modafinil , Nausea/prevention & control , Neuropsychological Tests , Pain/prevention & control , Piperidines/administration & dosage , Placebos , Propofol/administration & dosage , Psychomotor Agitation/prevention & control , Relaxation , Remifentanil , Sleep Stages/drug effects , Young AdultABSTRACT
Mechanical ventilation is known to induce bacterial translocation from the lung into the systemic circulation. This study determined the effect of immunoglobulin M (IgM)-enriched polyclonal immunoglobulins on bacteremia due to ventilation-induced translocation in an acute respiratory distress syndrome (ARDS) rat model with Klebsiella-induced pneumonia. After whole lung lavage, Sprague-Dawley rats intravenously received either a high dose or a low dose of an immunoglobulin preparation, or an albumin solution as control, followed by an intratracheal injection of a Klebsiella pneumoniae solution. Blood colony-forming units (CFUs) in the treatment groups were significantly lower during the 3-hour ventilation period compared to the control group. The authors conclude that IgM-enriched polyclonal immunoglobulins lead to a reduction of bacteria in blood of surfactant-deficient, ventilated rats infected with Klebsiella pneumoniae.
Subject(s)
Bacteremia/therapy , Immunoglobulin M/therapeutic use , Immunoglobulins, Intravenous/therapeutic use , Klebsiella Infections/complications , Klebsiella Infections/therapy , Klebsiella pneumoniae/physiology , Respiratory Distress Syndrome/complications , Animals , Antibodies, Bacterial/administration & dosage , Antibodies, Bacterial/immunology , Antibodies, Bacterial/therapeutic use , Bacteremia/complications , Bacteremia/immunology , Bacteremia/microbiology , Blood Gas Analysis , Blood Pressure , Bronchoalveolar Lavage , Colony Count, Microbial , Disease Models, Animal , Immune Sera/administration & dosage , Immune Sera/immunology , Immunization, Passive , Immunoglobulin M/administration & dosage , Immunoglobulin M/immunology , Immunoglobulins, Intravenous/administration & dosage , Immunoglobulins, Intravenous/immunology , Klebsiella Infections/immunology , Klebsiella Infections/microbiology , Rats , Rats, Sprague-Dawley , Respiration, ArtificialABSTRACT
We report the pre-operative preparation and anaesthetic management for resection of an intracerebral tumour during awake craniotomy in a 9-year-old boy. We believe this is the youngest patient reported to have undergone this procedure. The challenges of sedation and psychological care throughout the procedure are discussed. We conclude that the procedure can be performed safely and that it seems unacceptable to uphold an age restriction. We believe that it is the individual level of development of the child that determines suitability for this type of surgery.
Subject(s)
Brain Neoplasms/surgery , Conscious Sedation/methods , Craniotomy/methods , Glioblastoma/surgery , Neoplasm Recurrence, Local/surgery , Anesthesia, Local/methods , Child , Humans , Male , Monitoring, Intraoperative/methods , Neuropsychological TestsABSTRACT
During the first generalised epileptic attack, a patient suffered a humerus fracture which necessitated an operation. This patient also had a history of spontaneous lung emboli and an elevated anti-cardiolipin plasma level for which coumarin was prescribed but was stopped preoperatively. After induction of general anaesthesia for a total shoulder arthroplasty, the patient became hypotensive and the bispectral index recorded perioperatively dropped to 0. Postoperatively, the patient developed signs of a unilateral borderzone cerebral infarct in the area of the medial cerebral artery. The possible pathomechanisms involved are discussed. In cases of known cerebral pathology intraoperative hypotension should be avoided by at all costs. Patients with increased anti-cardiolipin antibody levels and who suffer from epileptic attacks have an increased risk of thromboembolic events.
Subject(s)
Anesthesia, General , Autoantibodies/immunology , Cardiolipins/immunology , Infarction, Middle Cerebral Artery/etiology , Intraoperative Complications/etiology , Anticoagulants/therapeutic use , Arthroplasty , Autoantibodies/analysis , Blood Coagulation Tests , Coumarins/therapeutic use , Electrocardiography/drug effects , Hemodynamics , Humans , Humeral Fractures/surgery , Magnetic Resonance Imaging , Male , Middle Aged , Shoulder/surgeryABSTRACT
BACKGROUND: Carbon dioxide (CO2) pneumoperitoneum (PP) increases mean arterial blood pressure (MAP) and systemic vascular resistance (SVR) but decreases stroke volume (SV) and cardiac output (CO). This study evaluated the hemodynamic effects of elevated intraabdominal pressure (IAP) occurring during laparoscopic donor nephrectomy (LDN). METHODS: Twenty-two patients undergoing LDN were investigated and hemodynamic parameters, P(v)CO2) (carbon dioxide partial pressure), and VCO2 (carbon dioxide production) were monitored during the procedure. Before and after PP, IAP was raised from 12 to 20 mmHg and the hemodynamic effects were measured every 30 s. RESULTS: During IAP of 12 mmHg and stable serum CO2, there was no change in SV compared to preinsufflation levels. When IAP was elevated from 12 to 20 mmHg, SV initially decreased (p < 05), followed by an increase in MAP and SVR (p < 0.05). CONCLUSION: This study shows that with the fluid and ventilation protocol used, PP has no significant effect on SV at an IAP of 12 mmHg, whereas increasing IAP to 20 mmHg does. In this study, the hemodynamic effects induced by CO2 PP of 12 mmHg are not due to changes in serum CO2. Compression of the venous system during a PP of 20 mmHg reduces preload, with an subsequent increase in SVR.
Subject(s)
Abdominal Cavity , Carbon Dioxide/pharmacology , Hemodynamics , Laparoscopy , Nephrectomy/methods , Pneumoperitoneum, Artificial , Pressure , Tissue and Organ Harvesting/methods , Adult , Aged , Blood Pressure/drug effects , Blood Volume , Carbon Dioxide/administration & dosage , Carbon Dioxide/adverse effects , Carbon Dioxide/blood , Diuresis/drug effects , Female , Hemodynamics/drug effects , Humans , Insufflation , Intraoperative Complications/etiology , Intraoperative Complications/prevention & control , Male , Middle Aged , Partial Pressure , Pneumoperitoneum, Artificial/adverse effects , Stroke Volume/drug effects , Vascular Resistance/drug effectsABSTRACT
Disturbances in lung function and lung mechanics are present after ventilation with high peak inspiratory pressures (PIP) and low levels of positive end-expiratory pressure (PEEP). Therefore, the authors investigated whether partial liquid ventilation can re-establish lung function after ventilation-induced lung injury. Adult rats were exposed to high PIP without PEEP for 20 min. Thereafter, the animals were randomly divided into five groups. The first group was killed immediately after randomization and used as an untreated control. The second group received only sham treatment and ventilation, and three groups received treatment with perfluorocarbon (10 mL x kg(-1), 20 mL x kg(-1), and 20 ml x kg(-1) plus an additional 5 mL x kg(-1) after 1 h). The four groups were maintained on mechanical ventilation for a further 2-h observation period. Blood gases, lung mechanics, total protein concentration, minimal surface tension, and small/large surfactant aggregates ratio were determined. The results show that in ventilation-induced lung injury, partial liquid ventilation with different amounts of perflubron improves gas exchange and pulmonary function, when compared to a group of animals treated with standard respiratory care. These effects have been observed despite the presence of a high intra-alveolar protein concentration, especially in those groups treated with 10 and 20 mL of perflubron. The data suggest that replacement of perfluorocarbon, lost over time, is crucial to maintain the constant effects of partial liquid ventilation.
Subject(s)
Intermittent Positive-Pressure Ventilation , Liquid Ventilation , Positive-Pressure Respiration , Pulmonary Alveolar Proteinosis/physiopathology , Animals , Dose-Response Relationship, Drug , Fluorocarbons/administration & dosage , Lung Volume Measurements , Male , Pulmonary Gas Exchange/physiology , Rats , Rats, Sprague-Dawley , Respiratory Mechanics/physiology , Work of Breathing/physiologyABSTRACT
OBJECTIVE: It has been demonstrated that pulmonary surfactant plays a role in the pathophysiology of ventilation-induced lung injury (VILI). Therefore, we investigated whether exogenous surfactant might restore lung function and lung mechanics in an established model of VILI. DESIGN: Prospective, randomized, animal study. SETTING: Experimental laboratory of a university. SUBJECTS: Twenty-four adult male Sprague-Dawley rats. INTERVENTIONS: First, a group of six animals were killed immediately after induction of anesthesia and used as healthy controls. Then, in 18 rats, VILI was induced by increasing peak inspiratory pressure (PIP) to 45 cmH2O without positive end-expiratory pressure (PEEP) for 20 min. Thereafter, animals were randomly divided into three groups of six animals each: one group was killed immediately after VILI and served as VILI-control. In the other two groups, ventilator settings were changed to a PIP of 30 cmH2O and a PEEP of 10 cmH2O, and a respiratory rate of 40 bpm. One group received a bolus of surfactant and the other group received no treatment. MEASUREMENTS AND RESULTS: Blood gas tension and arterial blood pressures were recorded every 30 min for 2 h. After the study period, a pressure-volume curve was recorded. Then, a broncho-alveolar lavage (BAL) was performed to determine protein content, minimal surface tension, and surfactant composition in the BAL fluid. Oxygenation, lung mechanics, surfactant function and composition were significantly improved in the surfactant-treated group compared to the ventilated and non-ventilated control groups. CONCLUSION: We conclude that exogenous surfactant can be used to treat VILI.
Subject(s)
Disease Models, Animal , Positive-Pressure Respiration/adverse effects , Pulmonary Surfactants/therapeutic use , Respiration, Artificial/adverse effects , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/etiology , Animals , Blood Gas Analysis , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/cytology , Drug Evaluation, Preclinical , Lung Volume Measurements , Male , Positive-Pressure Respiration/methods , Prospective Studies , Pulmonary Gas Exchange/drug effects , Pulmonary Surfactants/pharmacology , Random Allocation , Rats , Rats, Sprague-Dawley , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/physiopathology , Respiratory Mechanics/drug effectsABSTRACT
OBJECTIVES: To determine the effect on compartmentalization of the tumor necrosis factor (TNF)-alpha response in the lung and systemically after ventilation with high peak inspiratory pressure with and without positive end-expiratory pressure (PEEP). DESIGN AND SETTING: Prospective, randomized, animal study in an experimental laboratory of a university. SUBJECTS AND INTERVENTIONS: 85 male Sprague-Dawley rats. Lipopolysaccharide was given intratracheally or intraperitoneally to stimulate TNF-alpha production; control animals received a similar amount of saline. Animals were subsequently ventilated for 20 min in a pressure control mode with peak inspiratory pressure/PEEP ratio of either 45/0 or 45/10 (frequency 30 bpm, I/E ratio 1:2, FIO2 = 1). MEASUREMENTS AND RESULTS: Blood gas tension and arterial pressures were recorded at 1, 10, and 20 min after start of mechanical ventilation. After killing of the animals pressure-volume curves were recorded, and bronchoalveolar lavage (BAL) was performed for assessment of protein content and the small/large surfactant aggregate ratio. TNF-alpha was determined in serum and BAL. TNF-alpha levels were significantly increased after lipopolysaccharide stimulation; furthermore ventilation without PEEP resulted in a significant shift of TNF-alpha to the nonstimulated compartment as opposed to ventilation with a PEEP level of 10 cmH2O. CONCLUSIONS: Ventilation strategies which are known to induce ventilation-induced lung injury (VILI) disturb the compartmentalization of the early cytokines response in the lung and systemically. Furthermore, the loss of compartmentalization is a two-way disturbance, with cytokines shifting from the vascular side to the alveolar side and vice versa. A ventilation strategy (PEEP level of 10 cmH2O) which prevents VILI significantly diminished this shift in cytokines.
Subject(s)
Disease Models, Animal , Positive-Pressure Respiration/adverse effects , Pulmonary Alveoli/chemistry , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/metabolism , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/metabolism , Analysis of Variance , Animals , Blood Gas Analysis , Blood Pressure , Bronchoalveolar Lavage Fluid/chemistry , Inflammation , Lipopolysaccharides , Male , Positive-Pressure Respiration/methods , Prospective Studies , Random Allocation , Rats , Rats, Sprague-Dawley , Respiratory Distress Syndrome/physiopathology , Tidal Volume , Time FactorsABSTRACT
OBJECTIVE: To demonstrate that under well-defined conditions, pressure-controlled ventilators (PCV) allow settings that are as good as high-frequency oscillatory ventilators (HFOV) at preserving the function of exogenous surfactant in lung-lavaged rats. DESIGN: Experimental, comparative study. SETTING: Research laboratory of a large university. SUBJECTS: Sixteen adult male Sprague-Dawley rats (280-310 g). INTERVENTIONS: Lung injury was induced by repeated lavage. After last lavage, all animals received exogenous surfactant and were then randomly assigned to two groups (n = 8 per group). The first group received PCV with small pressure amplitudes and high positive end-expiratory pressure. The second group received HFOV. In both groups, an opening maneuver was performed by increasing airway pressure to improve PaO2/F(IO2) to > or =500 torr. MEASUREMENTS AND MAIN RESULTS: Blood gases were measured every 30 mins for 3 hrs. Airway pressures were measured with a tip catheter pressure transducer. At the end of the study period, a pressure-volume curve was recorded and a broncho-alveolar lavage was performed to determine protein content and surfactant composition. The results showed that arterial oxygenation in both groups could be kept >500 torr during the 3-hr study period by using a mean airway pressure of 13+/-3 cm H2O in PCV and 13+/-2 cm H2O in HFOV. Further, there were no differences in the Gruenwald index, protein influx, or ratio of small to large aggregates between the study groups. CONCLUSION: PCV with sufficient level of positive end-expiratory pressure and small driving pressure amplitudes is as effective as HFOV to maintain optimal gas exchange, to improve lung mechanics, and to prevent protein influx and conversion of large into small aggregates after exogenous surfactant therapy in lung-lavaged rats.
Subject(s)
High-Frequency Ventilation , Lung Diseases/physiopathology , Lung Diseases/therapy , Positive-Pressure Respiration , Pulmonary Surfactants/physiology , Animals , Blood Gas Analysis , Bronchoalveolar Lavage , Lung Diseases/blood , Lung Diseases/etiology , Male , Rats , Rats, Sprague-DawleyABSTRACT
BACKGROUND: Using an in vivo animal model of surfactant deficiency, the authors compared the effect of different ventilation strategies on oxygenation and inflammatory mediator release from the lung parenchyma. METHODS: In adult rats that were mechanically ventilated with 100% oxygen, acute lung injury was induced by repeated lung lavage to obtain an arterial oxygen partial pressure < 85 mmHg (peak pressure/positive end-expiratory pressure [PEEP] = 26/6 cm H2O). Animals were then randomly assigned to receive either exogenous surfactant therapy, partial liquid ventilation, ventilation with high PEEP (16 cm H2O), ventilation with low PEEP (8 cm H2O), or ventilation with an increase in peak inspiratory pressure (to 32 cm H2O; PEEP = 6 cm H2O). Two groups of healthy nonlavaged rats were ventilated at a peak pressure/PEEP of 32/6 and 32/0 cm H2O, respectively. Blood gases were measured. Prostacyclin (PGI2) and tumor necrosis factor-alpha (TNF-alpha) concentrations in serum and bronchoalveolar lavage fluid (BALF) as well as protein concentration in BALF were determined after 90 and 240 min and compared with mechanically ventilated and spontaneously breathing controls. RESULTS: Surfactant, partial liquid ventilation, and high PEEP improved oxygenation and reduced BALF protein levels. Ventilation with high PEEP at high mean airway pressure levels increased BALF PGI2 levels, whereas there was no difference in BALF TNF-alpha levels between groups. Serum PGI2 and TNF-alpha levels did not increase as a result of mechanical ventilation when compared with those of spontaneously breathing controls. CONCLUSIONS: Although alveolar protein concentration and oxygenation markedly differed with different ventilation strategies in this model of acute lung injury, there were no indications of ventilation-induced systemic PGI2 and TNF-alpha release, nor of pulmonary TNF-alpha release. Mechanical ventilation at high mean airway pressure levels increased PGI2 levels in the bronchoalveolar lavage-accessible space.
Subject(s)
Epoprostenol/biosynthesis , Lung/metabolism , Lung/physiology , Respiration, Artificial , Tumor Necrosis Factor-alpha/biosynthesis , 6-Ketoprostaglandin F1 alpha/blood , 6-Ketoprostaglandin F1 alpha/metabolism , Animals , Bronchoalveolar Lavage Fluid/chemistry , Carbon Dioxide/blood , Male , Oxygen/blood , Proteins/metabolism , Pulmonary Alveoli/metabolism , Rats , Rats, Sprague-Dawley , Respiratory Function Tests , Therapeutic IrrigationABSTRACT
OBJECTIVE: To demonstrate in experimental animals with respiratory insufficiency that under well-defined conditions, commercially available ventilators allow settings which are as effective as high-frequency oscillatory ventilators (HFOV), with respect to the levels of gas exchange, protein infiltration, and lung stability. DESIGN: Prospective, randomized, animal study. SETTING: Experimental laboratory of a university. SUBJECTS: 18 adult male Sprague-Dawley rats. INTERVENTIONS: Lung injury was induced by repeated whole-lung lavage. Thereafter, the animals were assigned to pressure-controlled ventilation (PCV) plus The Open Lung Concept (OLC) or HFOV plus OLC (HFO(OLC)). In both groups, an opening maneuver was performed by increasing airway pressures to improve the arterial oxygen tension/fractional inspired oxygen (PaO(2)/FIO(2)) ratio to L 500 mm Hg; thereafter, airway pressures were reduced to minimal values, which kept PaO(2)/FIO(2) L 500 mm Hg. Pressure amplitude was adjusted to keep CO(2) as close as possible in the normal range. MEASUREMENTS AND RESULTS: Airway pressure, blood gas tension, and arterial blood pressure were recorded every 30 min. At the end of the 3-h study period, a pressure-volume curve was recorded and bronchoalveolar lavage was performed to determine protein content. After the recruitment maneuver, the resulting mean airway pressure to keep a PaO(2)/FIO(2) L 500 mm Hg was 25 +/- 1.3 cm H(2)O during PCV(OLC) and 25 +/- 0.5 cm H(2)O during HFOV(OLC). Arterial oxygenation in both groups was above L 500 mm Hg and arterial carbon dioxide tension was kept close to the normal range. No differences in mean arterial pressure, lung mechanics and protein influx were found between the two groups. CONCLUSIONS: This study shows that in surfactant-deficient animals, PCV, in combination with a recruitment maneuver, opens atelectatic lung areas and keeps them open as effectively as HFOV.
Subject(s)
High-Frequency Ventilation , Lung/physiopathology , Positive-Pressure Respiration , Pulmonary Gas Exchange/physiology , Pulmonary Surfactants/deficiency , Respiratory Mechanics/physiology , Animals , High-Frequency Ventilation/instrumentation , High-Frequency Ventilation/methods , Male , Positive-Pressure Respiration/instrumentation , Positive-Pressure Respiration/methods , Prospective Studies , Random Allocation , Rats , Rats, Sprague-Dawley , Respiratory Insufficiency/physiopathology , Respiratory Insufficiency/therapy , Time Factors , Ventilators, MechanicalABSTRACT
Acute thermal trauma is well known to produce evidence of a "systemic inflammatory response" in vivo, as manifested by evidence of complement activation, appearance in plasma of a variety of inflammatory factors, and development of multi-organ injury. The current studies were focused on acute thermal injury of rat skin and factors responsible for accompanying activation of blood neutrophils. Acute thermal injury of rat skin resulted in a time-dependent loss of L-selectin and up-regulation of Mac-1 (CD11b/CD18) on blood neutrophils, with no changes in LFA-1 (CD11a/CD18). The loss of L-selectin was prevented by blockade of C5a but not by blockade of the alpha-chemokine, macrophage inflammatory protein-2 (MIP-2). C5a, the alpha chemokines, MIP-2 and keratinocyte-derived cytokine (KC), and platelet activating factor (PAF) contributed to up-regulation of blood neutrophil Mac-1. Blocking interventions against these mediators also blunted the degree of neutropenia developing after thermal trauma. These data suggest that activation of blood neutrophils after thermal trauma is related to the role of several chemotactic mediators. These studies may provide clues regarding factors responsible for development of the "systemic inflammatory response syndrome" after thermal injury in the experimental model employed.
Subject(s)
Burns/immunology , Chemotactic Factors/physiology , Neutrophil Activation/immunology , Receptors, Cell Surface , Receptors, G-Protein-Coupled , Animals , Antibodies, Blocking/pharmacology , Burns/metabolism , Burns/therapy , CD11 Antigens/biosynthesis , CD18 Antigens/biosynthesis , Cell Adhesion Molecules/biosynthesis , Chemokine CXCL2 , Chemokines , Complement C5a/antagonists & inhibitors , Complement C5a/immunology , Complement C5a/physiology , Cytokines/antagonists & inhibitors , Cytokines/physiology , Immune Sera/pharmacology , L-Selectin/biosynthesis , Leukocyte Count , Male , Monokines/antagonists & inhibitors , Monokines/immunology , Monokines/physiology , Neutrophils/immunology , Neutrophils/metabolism , Platelet Membrane Glycoproteins/antagonists & inhibitors , Rats , Rats, Long-Evans , Up-Regulation/immunologyABSTRACT
We have compared three treatment strategies, that aim to prevent repetitive alveolar collapse, for their effect on gas exchange, lung mechanics, lung injury, protein transfer into the alveoli and surfactant system, in a model of acute lung injury. In adult rats, the lungs were ventilated mechanically with 100% oxygen and a PEEP of 6 cm H2O, and acute lung injury was induced by repeated lung lavage to obtain a PaO2 value < 13 kPa. Animals were then allocated randomly (n = 12 in each group) to receive exogenous surfactant therapy, ventilation with high PEEP (18 cm H2O), partial liquid ventilation or ventilation with low PEEP (8 cm H2O) (ventilated controls). Blood-gas values were measured hourly. At the end of the 4-h study, in six animals per group, pressure-volume curves were constructed and bronchoalveolar lavage (BAL) was performed, whereas in the remaining animals lung injury was assessed. In the ventilated control group, arterial oxygenation did not improve and protein concentration of BAL and conversion of active to non-active surfactant components increased significantly. In the three treatment groups, PaO2 increased rapidly to > 50 kPa and remained stable over the next 4 h. The protein concentration of BAL fluid increased significantly only in the partial liquid ventilation group. Conversion of active to non-active surfactant components increased significantly in the partial liquid ventilation group and in the group ventilated with high PEEP. In the surfactant group and partial liquid ventilation groups, less lung injury was found compared with the ventilated control group and the group ventilated with high PEEP. We conclude that although all three strategies improved PaO2 to > 50 kPa, the impact on protein transfer into the alveoli, surfactant system and lung injury differed markedly.
Subject(s)
Pulmonary Surfactants/therapeutic use , Respiration, Artificial/methods , Respiratory Distress Syndrome/therapy , Animals , Bronchoalveolar Lavage , Carbon Dioxide/blood , Disease Models, Animal , Fluorocarbons/therapeutic use , Male , Oxygen/blood , Partial Pressure , Positive-Pressure Respiration , Rats , Rats, Sprague-Dawley , Respiratory Distress Syndrome/etiologyABSTRACT
OBJECTIVE: To investigate in a rat model of ventilation-induced lung injury whether metabolic changes in the lung are reflected by an increased purine concentration (adenosine, inosine, hypoxanthine, xanthine, and urate; an index of adenosine-triphosphate breakdown) of the bronchoalveolar lavage fluid and whether purine can, thus, indirectly serve as a marker of ventilation-induced lung injury. DESIGN: Prospective, randomized, controlled trial. SETTING: Research laboratory. SUBJECTS: Forty-two male Sprague-Dawley rats. INTERVENTIONS: Five groups of Sprague-Dawley rats were subjected to 6 mins of mechanical ventilation. One group was ventilated at a peak inspiratory pressure of 7 cm H2O and a positive end-expiratory pressure of 0 cm H2O. A second group was ventilated at a peak inspiratory pressure of 45 cm H2O and a positive end-expiratory pressure of 10 cm H2O. Three groups of Sprague-Dawley rats were ventilated at a peak inspiratory pressure of 45 cm H2O without positive end-expiratory pressure. Before mechanical ventilation, two of these groups received intratracheal administration of saline or exogenous surfactant at a dose of 100 mg/kg and one group received no intratracheal administration. A sixth group served as the nonventilated controls. MEASUREMENTS AND MAIN RESULTS: Bronchoalveolar lavage fluid was collected in which both purine concentration (microM; mean +/- SD) and protein concentration (mg/mL; mean +/- SD) were determined. Statistical differences were analyzed using the one-way analysis of variance (ANOVA) with a Student-Newman-Keul's post hoc test. Purine and protein concentrations were different between groups (ANOVA p value for purine and protein, <.0001). Both purine and protein concentrations in bronchoalveolar lavage fluid were increased in Group 45/0 (3.2 +/- 1.9 and 4.2 +/- 1.6, respectively) compared with Group 7/0 (0.4 +/- 0.1 [p < .05] and 0.4 +/- 0.2 [p < .001]) and controls (0.2 +/- 0.2 [p < .01] and 0.2 +/- 0.1 [p < .001]) and in Group 45/Na (5.8 +/- 2.5 and 4.2 +/- 0.5) compared with Group 7/0 (purine and protein, p < .001) and the controls (purine and protein, p < .001). Positive end-expiratory pressure prevented an increase in purine and protein concentrations in bronchoalveolar lavage fluid (0.4 +/- 0.3 and 0.4 +/- 0.2, respectively) compared with Group 45/0 (purine, p < .01; protein, p < .001) and Group 45/Na (purine and protein, p < .001). Surfactant instillation preceding lung overinflation reduced purine and protein concentration in bronchoalveolar lavage fluid (2.1 +/- 1.6 and 2.7 +/- 1.0) compared with Group 45/Na (purine, p < .001; protein (p < .01). Surfactant instillation reduced protein concentration compared with Group 45/0 (p < .01). CONCLUSIONS: This study shows that metabolic changes in the lung as a result of ventilation-induced lung injury are reflected by an increased level of purine in the bronchoalveolar lavage fluid and that purine may, thus, serve as an early marker for ventilation-induced lung injury. Moreover, the study shows that both exogenous surfactant and positive end-expiratory pressure reduce protein infiltration and that positive end-expiratory pressure decreases the purine level in bronchoalveolar lavage fluid after lung overinflation.
Subject(s)
Bronchoalveolar Lavage Fluid/chemistry , Positive-Pressure Respiration/adverse effects , Purines/analysis , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/metabolism , Analysis of Variance , Animals , Biomarkers/analysis , Disease Models, Animal , Male , Positive-Pressure Respiration/methods , Predictive Value of Tests , Prospective Studies , Proteins/analysis , Random Allocation , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Respiratory Distress Syndrome/pathology , Time FactorsABSTRACT
1. The use of pulmonary exogenous surfactant as a vehicle for intratracheally administered antibiotics to improve local antimicrobial therapy has been proposed. The present study investigated lung clearance rates in the rat of intratracheally instilled technetium labelled tobramycin with and without the addition of surfactant to the antibiotic solution. 2. The influence of surfactant on 99mTc-tobramycin lung clearance rates was studied dynamically with a gamma-camera in anaesthetized spontaneously breathing animals and in mechanically ventilated animals. 3. The results show that instillation of 99mTc-tobramycin with use of surfactant as vehicle significantly increases 99mTc-tobramycin lung clearance compared to instillation of 99mTc-tobramycin solution alone (P=0.006 between the two spontaneously breathing groups of animals and P=0.02 between the two ventilated groups of animals, ANOVA for repeated time measurements). The half life (t1/2) of composite clearance curves in spontaneous breathing animals was 147 min for animals receiving 99mTc-tobramycin versus 61 min for animals receiving 99mTc-tobramycin with surfactant. In mechanically ventilated animals this was 163 min versus 51 min, respectively. 4. It is concluded that exogenous surfactant, used as vehicle for intratracheally instilled 99mTc-tobramycin, increases lung clearance rate of 99mTc-tobramycin in rats.
Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Lung/metabolism , Pulmonary Surfactants/pharmacology , Radiopharmaceuticals/pharmacokinetics , Tobramycin/pharmacokinetics , Administration, Inhalation , Animals , Male , Metabolic Clearance Rate , Rats , Rats, Sprague-Dawley , Technetium Compounds/metabolismABSTRACT
It is being increasingly realized that modes of mechanical ventilation that result in end-inspiratory alveolar overstretching and/or repeated alveolar collapse and re-expansion disturb the normal fluid balance across the alveolocapillary membrane. The effects of this include disturbance of the integrity of the endothelium and epithelium and impairment of the surfactant system and are similar to those seen in acute respiratory distress syndrome (ARDS). There is now also evidence that these modes of mechanical ventilation may result in the translocation of bacteria from the lungs into the bloodstream and the release of inflammatory mediators from the lung tissue into the systemic circulation. It may thus be speculated that mechanical ventilation may contribute to the development of multiple organ failure (MOF). Therefore, during mechanical ventilation, alveolar overstretching and the repeated collapse and re-expansion of alveoli should be prevented by ventilation modes that open up the lung and keep the lung open and ventilate with the smallest possible pressure amplitude. For the future, monitoring techniques should be developed that can evaluate, on-line, whether or not these therapeutic directives are being achieved.
Subject(s)
Lung Injury , Respiration, Artificial/adverse effects , Animals , Cytokines/metabolism , Humans , Infant, Newborn , Lung/physiology , Pulmonary Alveoli/metabolism , Pulmonary Surfactants/metabolism , Respiratory Distress Syndrome, Newborn/metabolism , Respiratory Distress Syndrome, Newborn/therapy , Respiratory Function Tests , Water-Electrolyte BalanceABSTRACT
OBJECTIVE: High-frequency oscillation studies have shown that ventilation at high end-expiratory lung volumes combined with small volume cycles at high rates best preserves exogenous surfactant and gas exchange in lavaged lungs. We investigated whether surfactant composition and gas exchange can also be preserved by conventional modes of mechanical ventilation, which combine high levels of positive end-expiratory pressure (PEEP) with small pressure amplitudes. DESIGN: Prospective, randomized, nonblinded, controlled study. SETTING: Research laboratory. SUBJECTS: Thirty male Sprague-Dawley rats. INTERVENTIONS: Rats were lung-lavaged and treated with exogenous surfactant (100 mg/kg). After 5 mins, four different ventilator settings (F(IO)2 = 1.0) were applied for 3 hrs in four groups of rats [peak inspiratory pressure (cm H2O); static PEEP (cm H2O); inspiratory/expiratory ratio; frequency], as follows: 26/2/1:2/30 (group 26/2), 26/6/1:2/30 (group 26/6), 20/10/1:2/30 (group 20/ 10-static), and 20/6/7:3/130, creating an auto PEEP of 4 cm H2O (group 20/10-auto). MEASUREMENTS AND MAIN RESULTS: In all groups, Pao2 increased immediately to prelavage values after surfactant therapy. In group 26/2, Pao2 deteriorated to postlavage values within 30 mins when PEEP was decreased to 2 cm H2O, whereas Pao2 remained stable for 3 hrs in the other groups. The Paco2 increased in groups 26/2 and 20/10-static; Paco2 could not be reduced by increasing ventilation frequency to 130 in group 20/10-static. Groups 26/6 and 20/10-auto remained normocapnic. Bronchoalveolar lavage protein concentration was higher in groups 26/2 and 26/6 compared with groups 20/10-static and 20/10-auto. There was significantly more conversion of surface active large aggregates into nonactive small aggregates in group 26/2 compared with groups 20/10-static and 20/10-auto. CONCLUSIONS: We conclude that exogenous surfactant composition is preserved by conventional modes of mechanical ventilation that use small pressure amplitudes, and adequate oxygenation is maintained by high end-expiratory pressure levels. Effective carbon dioxide removal can be achieved by applying a ventilation mode that creates auto PEEP and not by a mode that applies the same level of PEEP by static PEEP only.
Subject(s)
Positive-Pressure Respiration/methods , Pulmonary Gas Exchange , Pulmonary Surfactants/metabolism , Animals , Male , Positive-Pressure Respiration, Intrinsic , Pulmonary Surfactants/therapeutic use , Rats , Rats, Sprague-Dawley , Respiration, Artificial/methodsABSTRACT
BACKGROUND: Changes in pulmonary edema infiltration and surfactant after intermittent positive pressure ventilation with high peak inspiratory lung volumes have been well described. To further elucidate the role of surfactant changes, the authors tested the effect of different doses of exogenous surfactant preceding high peak inspiratory lung volumes on lung function and lung permeability. METHODS: Five groups of Sprague-Dawley rats (n = 6 per group) were subjected to 20 min of high peak inspiratory lung volumes. Before high peak inspiratory lung volumes, four of these groups received intratracheal administration of saline or 50, 100, or 200 mg/kg body weight surfactant; one group received no intratracheal administration. Gas exchange was measured during mechanical ventilation. A sixth group served as nontreated, nonventilated controls. After death, all lungs were excised, and static pressure-volume curves and total lung volume at a transpulmonary pressure of 5 cm H2O were recorded. The Gruenwald index and the steepest part of the compliance curve (Cmax) were calculated. A bronchoalveolar lavage was performed; surfactant small and large aggregate total phosphorus and minimal surface tension were measured. In a second experiment in five groups of rats (n = 6 per group), lung permeability for Evans blue dye was measured. Before 20 min of high peak inspiratory lung volumes, three groups received intratracheal administration of 100, 200, or 400 mg/ kg body weight surfactant; one group received no intratracheal administration. A fifth group served as nontreated, nonventilated controls. RESULTS: Exogenous surfactant at a dose of 200 mg/kg preserved total lung volume at a pressure of 5 cm H2O, maximum compliance, the Gruenwald Index, and oxygenation after 20 min of mechanical ventilation. The most active surfactant was recovered in the group that received 200 mg/kg surfactant, and this dose reduced minimal surface tension of bronchoalveolar lavage to control values. Alveolar influx of Evans blue dye was reduced in the groups that received 200 and 400 mg/kg exogenous surfactant. CONCLUSIONS: Exogenous surfactant preceding high peak inspiratory lung volumes prevents impairment of oxygenation, lung mechanics, and minimal surface tension of bronchoalveolar lavage fluid and reduces alveolar influx of Evans blue dye. These data indicate that surfactant has a beneficial effect on ventilation-induced lung injury.