shock induction and treatment of hemodynamic instability in a porcine model using lps infusion and picco monitoring

LPS 주입을 통한 돼지의 내독소혈증의 용량 의존적 유도

Sepsis and septic shock rank among the leading causes of mortality in patients receiving intensive care treatment1,2,3. Sepsis arises when an infection triggers a dysregulated immune response resulting in multiorgan failure. It is characterized by life-threatening symptoms, including hemodynamic instability, respiratory distress, hepatic and renal failure, as well as cognitive impairment4,5. Septic shock represents a subset of sepsis with particularly severe symptoms that significantly increase mortality. These symptoms include persistent hypotension requiring vasopressor therapy and a serum lactate level exceeding 2 mmol&#8729;L-1&#160;4,5. Mortality rates in patients with septic shock have been estimated as high as 40%, even with hospital treatment1,3,5.
Gram-negative bacteria, such as Pseudomonas and Escherichia coli, often cause infections triggering this dysregulated immune response4. The underlying pathophysiological mechanisms are complex and not yet fully understood. One well-described aspect involves the activation of Toll-like receptors on immune cells by pathogen-associated molecular patterns (PAMPs), leading to the release of cytokines such as tumor necrosis factor-alpha (TNF&#945;) or Interleukin 1 (IL 1)4. One of these PAMPs is lipopolysaccharide (LPS), which constitutes a component of the cell membrane in gram-negative bacteria6. LPS has been employed in animal models to induce endotoxemia and endotoxemic shock7,8.
Animal models provide a controlled and standardized setting to develop and investigate novel treatment strategies. Due to its similar anatomy, immunological physiology, and comparable hemodynamic parameters, the pig model is particularly well-suited for studying the effects of endotoxemic shock9,10. Furthermore, standard medical equipment commonly used in human patients can be readily applied in pigs due to the similar size of their airways and blood vessels, facilitating instrumentation and hemodynamic monitoring.
With this protocol, we provide an experimental model for endotoxemic shock in pigs by intravenously infusing LPS derived from E. coli. To monitor the effects, we measured hemodynamic and pulmonary parameters, including arterial blood pressure, heart rate, peripheral oxygen saturation, pulmonary arterial pressure, and airway pressure. To evaluate the influence of endotoxemia on cerebral oxygen supply, we used near-infrared spectrometry (NIRS). With this method, the cerebral oxygen saturation can be evaluated via an adhesive electrode applied to the forehead11.

저자 스포트라이트: 혈류역학 및 호흡 부전을 연구하기 위한 돼지의 실험적 내독소혈성 쇼크 유도

돼지 내독소혈증 쇼크 모델로서의 지질다당류 주입

With this protocol, we induce experimental endotoxemic shock in pigs. We were able to reliably cause symptoms of endotoxemia, such as hemodynamic instability and respiratory failure. Lipopolysaccharide is a toxic substance.When working with lipopolysaccharide, it is essential always to wear gloves, protective goggles, a mask, and a lab coat. This protocol provides an easy and reliable way to induce endotoxemia. Because of their similar anatomy and physiology, pigs are particularly well-suited for this kind of research as standard medical equipment may be used.Using this protocol, we will be able to study the effects of different ventilation strategies in respiratory failure and lung damage during endotoxemic shock.

LPS 주입 및 PiCCO 모니터링을 사용한 돼지 모델의 혈류역학적 불안정성의 충격 유도 및 치료

Swan-Ganz 카테터를 폐동맥에 삽입한 후 마취된 돼지를 30분 동안 안정시킵니다. 그런 다음 기준 혈류역학 측정값을 얻습니다. 지질다당류 또는 LPS 1kg당 150마이크로그램을 30분 동안 투여합니다.동맥 및 폐동맥 혈압, 심박수 및 환기와 같은 혈역학적 매개변수를 모니터링합니다. 그런 다음 시간당 킬로그램당 15마이크로그램의 LPS 주입 속도로 혈류역학적 매개변수를 모니터링합니다. PiCCO 모니터에서 열희석 버튼을 누른 후 중심정맥압 또는 CVP 입력 버튼을 누르고 현재 CVP 값을 입력한 후 시작 버튼을 누릅니다.메시지가 표시되면 Swan-Ganz 카테터에 연결된 주입 온도 센서에 10ml의 냉식염수를 주입합니다. 심장 지수, 전체 이완기 말기 지수, 혈관 외 폐수 지수를 측정한 후 흐름도에 따라 혈역학적 불안정성 치료를 적용합니다. 부피 부하의 경우 200mL의 균형 잡힌 전해질 용액을 빠르게 주입합니다.카테콜아민 요법의 경우 노르에피네프린 주입 속도를 시간당 킬로그램당 1마이크로그램씩 증가시킵니다. 평균 동맥 혈압은 LPS 주입 후 감소했으나 수액 소생술이나 노르에피네프린 주입을 통해 수은 60mm 이상으로 유지되었다. 동물은 심장 지수의 감소와 심박수의 증가를 보였으며, 이는 쇼크 상태 동안 혈역학적 불안정성을 나타냅니다.폐 손상은 산소 분압과 동맥혈 흡기 산소 분율 비율의 감소와 폐동맥압의 증가로 나타났다. 뇌 산소 공급도 쇼크 유도 후 감소했다. 동물들은 또한 산증과 젖산 수치 증가를 보였다.

shock-induction-treatment-hemodynamic-instability-porcine-model-using

Research

JoVE Journal

Medicine

Shock Induction and Treatment of Hemodynamic Instability in a Porcine Model Using LPS Infusion and PiCCO Monitoring

81 조회수.  University Medical Center of the Johannes Gutenberg-University. Swan-Ganz 카테터를 폐동맥에 삽입한 후 마취된 돼지를 30분 동안 안정시킵니다. 그런 다음 기준 혈류역학 측정값을 얻습니다. 지질다당류 또는 LPS 1kg당 150마이크로그램을 30분 동안 투여합니다.동맥 및 폐동맥 혈압, 심박수 및 환기와 같은 혈역학적 매개변수를 모니터링합니다. 그런 다음 시간당 킬로그램당 15마이크로그램의 LPS 주입 속도로 혈류역학적 매개변수를 모니터...

비디오: LPS 주입 및 PiCCO 모니터링을 사용한 돼지 모델의 혈류역학적 불안정성의 충격 유도 및 치료

Lipopolysaccharide Infusion as a Porcine Endotoxemic Shock Model

Sepsis and septic shock are frequently encountered in patients treated in intensive care units (ICUs) and are among the leading causes of death in these patients. It is caused by a dysregulated immune response to an infection. Even with optimized treatment, mortality rates remain high, which makes further insights into the pathophysiology and new treatment options necessary. Lipopolysaccharide (LPS) is a component of the cell membrane of gram-negative bacteria, which are often responsible for infections causing sepsis and septic shock. 
The severity and high mortality of sepsis and septic shock make standardized experimental studies in humans impossible. Thus, an animal model is needed for further studies. The pig is especially well suited for this purpose as it closely resembles humans in anatomy, physiology, and size. 
This protocol provides an experimental model for endotoxemic shock in pigs by LPS infusion. We were able to reliably induce changes frequently observed in septic shock patients, including hemodynamic instability, respiratory failure, and acidosis. This will allow researchers to gain valuable insight into this highly relevant condition and evaluate new therapeutic approaches in an experimental setting.

We provide a protocol for an experimental endotoxemic shock model in pigs by infusion of lipopolysaccharide.

Sepsis and septic shock are frequently encountered in patients treated in intensive care units (ICUs) and are among the leading causes of death in these ...

연구

의학

Instrumentation and Monitoring Techniques in Femoral Vascular Access for Hemodynamic Assessment in a Porcine Model

To begin, place the anesthetized pig supine on a working platform. Apply an alcoholic disinfectant to the inguinal area and wipe it with a sterile swab. Then apply disinfectant and wait three minutes before placing a sterile fenestrated drape over the inguinal area.Using ultrasound, identify the femoral blood vessels and visualize them longitudinally. Next, puncture the femoral vein with a syringe attached to the needle and confirm venous puncture with slow-flowing, dark red blood. Insert the wire into the vein and remove the needle while leaving the wire in place.Then puncture the artery with a syringe attached to the needle for continuous aspiration. Confirm the arterial puncture with bright red, pulsating blood. Remove the syringe from the artery and insert the prepared wire.Then remove the needle while leaving the wire in place. Using ultrasound, visualize the femoral vessels to confirm the correct positioning of both wires. Next, use Seldinger's technique to insert the arterial introducer sheath into the femoral artery, and the venous introducer sheath into the femoral vein.To confirm proper positioning, draw the blood from the arterial and central venous lines for blood gas analysis. Next, flush the lines with saline to prevent clot formation. Secure the lines to the skin using surgical sutures to prevent dislocation.Connect the arterial and central venous lines to transducers for hemodynamic measurements. Insert a pulse contour cardiac output, or PICO catheter, into the arterial introducer sheath. Connect the catheter to the arterial pressure transducer and the temperature interface cable of the PICO monitor.While continuously measuring pressure, insert the Swan-Ganz catheter into the central venous inducer sheath. Inflate the balloon once the catheter is inserted approximately 30 centimeters, and upon the appearance of a central venous pressure curve. Slowly advance the catheter into the central venous introducer sheath while monitoring the pressure curve.Once the catheter enters the right ventricle, examine for a pulse curve with a high systolic and low diastolic value. To confirm the placement of the catheter in the pulmonary artery, advance the catheter further and look for a consistent systolic and an increased diastolic value. Fix the catheter in position and connect the injectate temperature sensor of the PICO system to the proximal lumen of the Swan-Ganz catheter.

돼지 모델의 혈류역학적 평가를 위한 대퇴골 혈관 접근의 계측 및 모니터링 기법

After inserting the Swan-Ganz catheter into the pulmonary artery, allow the anesthetized pig to stabilize for 30 minutes. Then obtain the baseline hemodynamic measurements. Administer 150 micrograms per kilogram of lipopolysaccharide or LPS for 30 minutes.Monitor the hemodynamic parameters such as arterial and pulmonary arterial blood pressure, heart rate, and ventilation. Then monitor the hemodynamic parameters at an LPS infusion rate of 15 micrograms per kilogram per hour. On the PiCCO monitor, press the thermodilution button, then press the button for central venous pressure or CVP input, and enter the current CVP value before pressing the Start button.When prompted, inject 10 milliliters of cold saline solution into the injectate temperature sensor connected to the Swan-Ganz catheter. After measuring cardiac index, global end-diastolic index, and extravascular lung water index, apply hemodynamic instability treatment according to the flow chart. In case of volume loading, rapidly infuses 200 milliliters of balanced electrolyte solution.For catecholamine therapy, increase the norepinephrine infusion rate by one microgram per kilogram per hour. Mean arterial blood pressure decreased following LPS infusion, but was maintained above 60 millimeters of mercury through fluid resuscitation or norepinephrine infusion. The animals demonstrated a decrease in cardiac index and an increase in heart rate, indicating hemodynamic instability during the shock state.Lung damage was indicated by a decrease in the partial pressure of oxygen and the arterial blood inspiratory oxygen fraction ratio, and an increase in pulmonary artery pressure. Cerebral oxygenation also decreased following the induction of shock. The animals also exhibited acidosis and increasing lactate levels.