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

Summary

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.

Abstract

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 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.

Introduction

Massive blood loss is among the main causes of injury-related deaths^1,2,3. 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 generation^5,

Protocol

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 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-established model for hemorrhagic shock. Seven anesthetized male pigs (Sus scrofa domestica) with a mean weight of 28 ± 2 kg and an age of 2....

Results

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.......

Discussion

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.......

Materials

List of materials used in this article

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