Name: standardized hemorrhagic shock induction guided by cerebral oximetry and extended hemodynamic monitoring in pigs
Uploaded: 2019-05-21T13:00:00
Description: Watch this Scientific Journal Video about Standardized Hemorrhagic Shock Induction Guided by Cerebral Oximetry and Extended Hemodynamic Monitoring in Pigs at JoVE.com

The authors want to thank Dagmar Dirvonskis for her excellent technical support.

The experiments in this protocol were approved by the State and Institutional Animal Care Committee (Landesuntersuchungsamt Rheinland-Pfalz, Koblenz, Germany; Chairperson: Dr. Silvia Eisch-Wolf; reference number: 23 177-07/G 14-1-084; 02.02.2015). The experiments were conducted in accordance with the Animal Research&#160;Reporting of In Vivo Experiments (ARRIVE) guidelines. The study was planned and conducted between November 2015 and March 2016. After extended literature research, the pig model was chosen as a well-esta...

The protocol describes one method of inducing hemorrhagic shock via controlled arterial bleeding in pigs that is guided by systemic hemodynamics, as well as by cerebral microcirculatory impairment. Shock conditions were achieved by a calculated blood withdrawal of 25-35 mL kg-1 and confirmed by the mentioned composite of surrogate parameters indicating considerable cardio-circulatory failure. If untreated, this procedure was lethal within 2 h in 66% of the animals, which underlines the severity and reproducibi...

Massive blood loss is among the main causes of injury-related deaths1,2,3. The loss of circulatory fluid and oxygen carriers leads to hemodynamic failure and severe oxygen undersupply and can cause irreversible organ failure and death. The severity level of shock is influenced by additional factors like hypothermia, coagulopathy, and acidosis4. Particularly the brain, but also the kidneys lack compensation capacity due to high oxygen demand and the incapability of adequate anaerobic energy generation5,6. For therapeutic purposes, fast and immediate action is pivotal. In clinical practice, fluid resuscitation with a balanced electrolyte solution is the first option for treatment, followed by the administration of red blood cell concentrates and fresh frozen plasma. Thrombocyte concentrates, catecholamines, and the optimization of coagulation and the acid-base status support the therapy to regain normal physiological conditions after sustained trauma. This concept focuses on the restoration of hemodynamics and macrocirculation. Several studies, however, show that microcirculatory perfusion does not recover simultaneously with the macrocirculation. Especially, cerebral perfusion remains impaired and further oxygen undersupply may occur7,8.
The use of animal models allows scientists to establish novel or experimental strategies. The comparable anatomy, homology, and physiology of pigs and humans enable conclusions on specific pathological factors. Both species have a similar metabolic system and response to pharmacologic treatments. This is a great advantage in comparison to small animal&#160;models where differences in blood volume, hemodynamics, and overall physiology make it almost impossible to mimic a clinical scenario9. Furthermore, authorized medical equipment and consumables can be easily used in porcine models. Additionally, it is easily possible to obtain pigs from commercial suppliers, which allows a high diversity of genetics and phenotypes and is cost reducing10. The model of blood withdrawal via vessel cannulation is quite common11,12,13,14,15.
In this study, we extend the concept of hemorrhagic shock induction via arterial blood withdrawal with an exact titration of hemodynamic failure and cerebral oxygenation impairment. Hemorrhagic shock is achieved if the cardiac index and mean arterial pressure drops below 40% of the baseline value, which has been shown to cause considerable deterioration of the cerebral regional oxygenation saturation8. Pulse contour cardiac output (PiCCO) measurement is used for continuous hemodynamic monitoring. First, the system has to be calibrated by transpulmonary thermodilution, which enables the calculation of the cardiac index of the extravascular lung water content and the global end-diastolic volume. Subsequently, the continuous cardiac index is calculated by pulse contour analysis and also provides dynamic preload parameters like pulse pressure and stroke volume variation.
This technique is well established in clinical and experimental settings.Near-infrared spectroscopy (NIRS) is a clinically and experimentally established method to monitor changes in cerebral oxygen supply in real-time. Self-adherent sensors are attached to the left and right forehead and calculate the cerebral oxygenation non-invasively in the cerebral frontal cortex. Two wavelengths of infrared light (700 and 900 nm) are emitted and detected by the sensors after being reflected from the cortex tissue. To assess the cerebral oxygen content, contributions of arterial and venous blood are calculated in 1:3 relations and updated in 5 s intervals. The sensitivity in depth of 1-4 cm is exponential decreasing and influenced by the penetrated tissue (e.g., skin and bone), although the skull is translucent to infrared light. The technique facilitates quick therapeutic actions to prevent patients from adverse outcomes like delirium or hypoxic cerebral injury and serves as the target parameter in case of impaired cardiac output16,17. The combination of both techniques during experimental shock enables an exact titration of macrocirculation, as well as cerebral microcirculatory impairment, to study this life-threatening event.

<table border="0" cellpadding="0" cellspacing="0" style="width:824px;" width="825">
	<tbody>
		<tr height="42">
			<td height="42" style="height:42px;width:166px;">3-way-stopcock blue</td>
			<td style="width:258px;">Becton Dickinson Infusion Therapy AB Helsingborg, Sweden</td>
			<td style="width:150px;">394602</td>
			<td style="width:252px;">Drug administration</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:166px;">3-way-stopcock red</td>
			<td style="width:258px;">Becton Dickinson Infusion Therapy AB Helsingborg, Sweden</td>
			<td style="width:150px;">394605</td>
			<td style="width:252px;">Drug administration/Shock induction</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:166px;">Atracurium</td>
			<td style="width:258px;">Hikma Pharma GmbH , Martinsried</td>
			<td>AM03AC04*</td>
			<td style="width:252px;">Anesthesia</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:22px;width:166px;">Canula 20 G</td>
			<td style="width:258px;">Becton Dickinson S.A. Carretera Mequinenza Fraga, Spain</td>
			<td style="width:150px;">301300</td>
			<td style="width:252px;">Vascular access</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:166px;">Datex Ohmeda S5</td>
			<td style="width:258px;">GE Healthcare Finland Oy, Helsinki, Finland</td>
			<td>-</td>
			<td style="width:252px;">Hemodynamic monitor</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:166px;">Desinfection&#160;</td>
			<td style="width:258px;">Sch&#252;lke &#38; Mayr GmbH, Germany</td>
			<td>104802</td>
			<td style="width:252px;">Desinfection&#160;</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:166px;">Heidelberger Verl&#228;ngerung 75CM</td>
			<td style="width:258px;">Fresenius Kabi Deutschland GmbH</td>
			<td>2873112 &#160;</td>
			<td style="width:252px;">Drug administration/Shock induction</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;">INVOS 5100C Cerebral</td>
			<td style="width:258px;">Medtronic PLC, USA</td>
			<td>-</td>
			<td style="width:252px;">Monitore for cerebral regional oxygenation&#160;</td>
		</tr>
		<tr height="83">
			<td height="83" style="height:83px;width:166px;">INVOS Cerebral/Somatic Oximetry Adult Sensors</td>
			<td style="width:258px;">Medtronic PLC, USA</td>
			<td style="width:150px;">20884521211152</td>
			<td style="width:252px;">Monitoring of the cerebral regional oxygenation&#160;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:166px;">Endotracheal tube</td>
			<td style="width:258px;">Teleflex Medical Sdn. Bhd, Malaysia</td>
			<td style="width:150px;">112482</td>
			<td style="width:252px;">Intubation</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:166px;">Endotracheal tube introducer</td>
			<td style="width:258px;">&#160; Wirutec GmbH, Sulzbach, Germany</td>
			<td>5033062</td>
			<td style="width:252px;">Intubation</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:166px;">Engstr&#246;m Carestation</td>
			<td style="width:258px;">GE Heathcare, Madison USA</td>
			<td style="width:150px;">-</td>
			<td style="width:252px;">Ventilator</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:166px;">Fentanyl</td>
			<td style="width:258px;">Janssen-Cilag GmbH, Neuss</td>
			<td style="width:150px;">AA0014*</td>
			<td style="width:252px;">Anesthesia</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:166px;">Gloves</td>
			<td style="width:258px;">Paul Hartmann, Heidenheim, Germany</td>
			<td>9422131</td>
			<td style="width:252px;">Self-protection</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:166px;">Incetomat-line 150 cm</td>
			<td style="width:258px;">Fresenius, Kabi GmbH, Bad Homburg, Germany</td>
			<td style="width:150px;">9004112</td>
			<td style="width:252px;">Drug administration</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:166px;">Ketamine</td>
			<td style="width:258px;">Hameln Pharmaceuticals GmbH, Zofingen, Schweiz</td>
			<td style="width:150px;">AN01AX03*</td>
			<td style="width:252px;">Sedation</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:166px;">Laryngoscope</td>
			<td style="width:258px;">Teleflex Medical Sdn. Bhd, Malaysia</td>
			<td style="width:150px;">671067-000020</td>
			<td style="width:252px;">Intubation</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:166px;">Logical pressure monitoring system</td>
			<td style="width:258px;">Smith- Medical GmbH,&#160; Minneapolis, USA</td>
			<td>MX9606</td>
			<td style="width:252px;">Hemodynamic monitor</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:166px;">Logicath 7 Fr 3-lumen 30cm</td>
			<td style="width:258px;">Smith- Medical GmbH,&#160; Minneapolis, USA</td>
			<td>MXA233x30x70-E</td>
			<td style="width:252px;">Vascular access/Drug administration</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:22px;width:166px;">Masimo Radical 7</td>
			<td style="width:258px;">Masimo Corporation, Irvine, USA</td>
			<td style="width:150px;">-</td>
			<td style="width:252px;">Hemodynamic monitor</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:166px;">Mask for ventilating dogs</td>
			<td style="width:258px;">Henry Schein, Melville, USA</td>
			<td style="width:150px;">730-246</td>
			<td style="width:252px;">Ventilation</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:166px;">Original Perfusor syringe 50ml Luer Lock</td>
			<td style="width:258px;">B.Braun Melsungen AG, Melsungen, Germany</td>
			<td>8728810F</td>
			<td style="width:252px;">Drug administration</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:166px;">PICCO Thermodilution. F5/20CM EW&#160;</td>
			<td style="width:258px;">MAQUET Cardiovascular GmbH, Rastatt, Germany</td>
			<td>PV2015L20-A &#160;</td>
			<td style="width:252px;">Hemodynamic monitor</td>
		</tr>
		<tr height="104">
			<td height="104" style="height:104px;width:166px;">Percutaneous sheath introducer set 8,5 und 9 Fr, 10 cm with integral haemostasis valve/sideport</td>
			<td style="width:258px;">Arrow international inc., Reading, USA</td>
			<td>AK-07903</td>
			<td style="width:252px;">Vascular access/Shock induction</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:166px;">Perfusor FM Braun</td>
			<td style="width:258px;">B.Braun Melsungen AG, Melsungen, Germany</td>
			<td>8713820</td>
			<td style="width:252px;">Drug administration</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:166px;">Potassium chloride</td>
			<td style="width:258px;">Fresenius, Kabi GmbH, Bad Homburg, Germany</td>
			<td>6178549</td>
			<td style="width:252px;">Euthanasia</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:166px;">Propofol 2%</td>
			<td style="width:258px;">Fresenius, Kabi GmbH, Bad Homburg, Germany</td>
			<td style="width:150px;">&#160; AN01AX10*</td>
			<td style="width:252px;">Anesthesia</td>
		</tr>
		<tr height="45">
			<td height="45" style="height:45px;width:166px;">&#160;Pulse Contour Cardiac Output (PiCCO2)&#160;</td>
			<td style="width:258px;">Pulsion Medical Systems, Feldkirchen, Germany</td>
			<td>-</td>
			<td style="width:252px;">Hemodynamic monitor</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:166px;">Sonosite Micromaxx Ultrasoundsystem</td>
			<td style="width:258px;">Fujifilm, Sonosite Bothell, Bothell, USA&#160;</td>
			<td style="width:150px;">-</td>
			<td style="width:252px;">Vascular access</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:166px;">Stainless Macintosh Size 4</td>
			<td style="width:258px;">Teleflex Medical Sdn. Bhd, Perak,&#160; Malaysia</td>
			<td style="width:150px;">670000</td>
			<td style="width:252px;">Intubation</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:166px;">Sterofundin</td>
			<td style="width:258px;">B.Braun Melsungen AG, Melsungen, Germany</td>
			<td style="width:150px;">AB05BB01*</td>
			<td style="width:252px;">balanced electrolyte infusion</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:166px;">Stresnil 40mg/ml&#160;&#160;</td>
			<td style="width:258px;">Lilly Germany GmbH, Wiesbaden, Germany</td>
			<td style="width:150px;">QN05AD90</td>
			<td style="width:252px;">Sedation</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:166px;">Syringe 10 mL</td>
			<td style="width:258px;">Becton Dickinson S.A. Carretera Mequinenza Fraga, Spain</td>
			<td>309110</td>
			<td style="width:252px;">Drug administration</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:166px;">Syringe 2 mL</td>
			<td style="width:258px;">Becton Dickinson S.A. Carretera Mequinenza Fraga, Spain</td>
			<td>300928</td>
			<td style="width:252px;">Drug administration</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:166px;">Syringe 20 mL</td>
			<td style="width:258px;">Becton Dickinson S.A. Carretera Mequinenza Fraga, Spain</td>
			<td style="width:150px;">300296</td>
			<td style="width:252px;">Drug administration</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:166px;">Syringe 5 mL</td>
			<td style="width:258px;">Becton Dickinson S.A. Carretera Mequinenza Fraga, Spain</td>
			<td>309050</td>
			<td style="width:252px;">Drug administration</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:166px;">venous catheter 22G</td>
			<td style="width:258px;">B.Braun Melsungen AG, Melsungen, Germany</td>
			<td>4269110S-01</td>
			<td style="width:252px;">Vascular access</td>
		</tr>
		<tr height="21">
			<td colspan="2" height="21" style="height:21px;width:423px;">*ATC:&#160; Anatomical Therapeutic Chemical / Defined Daily Dose Classification&#160;</td>
			<td style="width:150px;"></td>
			<td style="width:252px;"></td>
		</tr>
	</tbody>
</table>

standardized hemorrhagic shock induction guided by cerebral oximetry and extended hemodynamic monitoring in pigs

Hemorrhagic shock ranks among the main reasons for severe injury-related death. The loss of circulatory volume and oxygen carriers can lead to an insufficient oxygen supply and irreversible organ failure. The brain exerts only limited compensation capacities and is particularly at high risk of severe hypoxic damage.This article demonstrates the reproducible induction of life-threatening hemorrhagic shock in a porcine model by means of calculated blood withdrawal. We titrate shock induction guided by near-infrared spectroscopy&#160;and extended hemodynamic monitoring to display systemic circulatory failure, as well as cerebral microcirculatory oxygen depletion. In comparison to similar models that primarily focus on predefined removal volumes for shock induction, this approach highlights a titration by means of the resulting failure of macro- and microcirculation.

After starting the shock induction, a short time of compensation can be registered. With ongoing blood removal, the aforementioned cardio-circulatory decompensation, as monitored by a significant decrease of crSO2, the cardiac index, the intrathoracic blood volume index, and the global end-diastolic volume index (Figure 2, Figure 3, and Figure 4), occurs. Furthermore, significant tachycard...

Watch this Scientific Journal Video about Standardized Hemorrhagic Shock Induction Guided by Cerebral Oximetry and Extended Hemodynamic Monitoring in Pigs at JoVE.com

Standardized Hemorrhagic Shock Induction Guided by Cerebral Oximetry and Extended Hemodynamic Monitoring in Pigs

Hemorrhagic shock is a severe complication in seriously injured patients, which leads to life-threatening oxygen undersupply. We present a standardized method to induce hemorrhagic shock via blood withdrawal in pigs that is guided by hemodynamics and microcirculatory cerebral oxygenation.

Hemorrhagic shock ranks among the main reasons for severe injury-related death. The loss of circulatory volume and oxygen carriers can lead to an ...

Research

JoVE Journal

Medicine

Fixed Volume or Fixed Pressure: A Murine Model of Hemorrhagic Shock

It is common knowledge that severe blood loss and traumatic injury can lead to a cascade of detrimental signaling events often resulting in mortality. 1, ...

Optimized System for Cerebral Perfusion Monitoring in the Rat Stroke Model of Intraluminal Middle Cerebral Artery Occlusion

The translational potential of pre-clinical stroke research depends on the accuracy of experimental modeling. Cerebral perfusion monitoring in animal ...

Lesion Explorer: A Video-guided, Standardized Protocol for Accurate and Reliable MRI-derived Volumetrics in Alzheimer's Disease and Normal Elderly

Obtaining in vivo human brain tissue volumetrics from MRI is often complicated by various technical and biological issues. These challenges are ...

Monitoring of Systemic and Hepatic Hemodynamic Parameters in Mice

The use of mouse models in experimental research is of enormous importance for the study of hepatic physiology and pathophysiological disturbances. ...

Uncontrolled Hemorrhagic Shock Modeled via Liver Laceration in Mice with Real Time Hemodynamic Monitoring

Uncontrolled hemorrhage is an important cause of preventable deaths among trauma patients. We have developed a murine model of uncontrolled hemorrhage via ...

Induction and Micro-CT Imaging of Cerebral Cavernous Malformations in Mouse Model

Mutations in the CCM1 (aka KRIT1), CCM2, or CCM3 (aka PDCD10) gene cause cerebral cavernous malformation (CCM) in humans. Mouse models of CCM disease have ...

Invasive Hemodynamic Monitoring of Aortic and Pulmonary Artery Hemodynamics in a Large Animal Model of ARDS

One of the leading causes of morbidity and mortality in patients with heart failure is right ventricular (RV) dysfunction, especially if it is due to ...

Complete and Partial Aortic Occlusion for the Treatment of Hemorrhagic Shock in Swine

Hemorrhage remains the leading cause of preventable deaths in trauma. Endovascular management of non-compressible torso hemorrhage has been at the ...

Complete and Partial Resuscitative Endovascular Balloon Occlusion of the Aorta for Hemorrhagic Shock

Resuscitative endovascular balloon occlusion of the aorta (REBOA) devices grew out of a military-civilian partnership to develop new capabilities for ...

Drug Treatment by Central Venous Catheter in a Mouse Model of Angiotensin II Induced Abdominal Aortic Aneurysm and Monitoring by 3D Ultrasound

Since pharmaceutical treatment options are lacking in the clinical management of abdominal aortic aneurysm (AAA), animal models, in particular mouse ...