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Resuscitation with whole blood or blood components improves survival and lessens the pathophysiological burden of trauma and haemorrhagic shock in a pre-clinical porcine model. Eur J Trauma Emerg Surg 2023; 49:227-239. [PMID: 35900383 PMCID: PMC9925484 DOI: 10.1007/s00068-022-02050-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 06/30/2022] [Indexed: 11/03/2022]
Abstract
PURPOSE In military trauma, disaster medicine, and casualties injured in remote locations, times to advanced medical and surgical treatment are often prolonged, potentially reducing survival and increasing morbidity. Since resuscitation with blood/blood components improves survival over short pre-surgical times, this study aimed to evaluate the quality of resuscitation afforded by blood/blood products or crystalloid resuscitation over extended 'pre-hospital' timelines in a porcine model of militarily relevant traumatic haemorrhagic shock. METHODS This study underwent local ethical review and was done under the authority of Animals (Scientific Procedures) Act 1986. Forty-five terminally anaesthetised pigs received a soft tissue injury to the right thigh, haemorrhage (30% blood volume and a Grade IV liver injury) and fluid resuscitation initiated 30 min later [Group 1 (no fluid); 2 (0.9% saline); 3 (1:1 packed red blood cells:plasma); 4 (fresh whole blood); or 5 (plasma)]. Fluid (3 ml/kg bolus) was administered during the resuscitation period (maximum duration 450 min) when the systolic blood pressure fell below 80 mmHg. Surviving animals were culled with an overdose of anaesthetic. RESULTS Survival time was significantly shorter for Group 1 compared to the other groups (P < 0.05). Despite the same triggers for resuscitation when compared to blood/blood components, saline was associated with a shorter survival time (P = 0.145), greater pathophysiological burden and significantly greater resuscitation fluid volume (P < 0.0001). CONCLUSION When times to advanced medical care are prolonged, resuscitation with blood/blood components is recommended over saline due to the superior quality and stability of resuscitation achieved, which are likely to lead to improved patient outcomes.
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Ordoñez CA, Parra MW, Serna JJ, Rodríguez-Holguin F, García A, Salcedo A, Caicedo Y, Padilla N, Pino LF, Hadad AG, Herrera MA, Millán M, Quintero-Barrera L, Hernández-Medina F, Ferrada R, Brenner M, Rasmussen T, Scalea T, Ivatury R, Holcomb JB. Damage control resuscitation: REBOA as the new fourth pillar. COLOMBIA MEDICA (CALI, COLOMBIA) 2020; 51:e4014353. [PMID: 33795897 PMCID: PMC7968430 DOI: 10.25100/cm.v51i4.4353] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Damage Control Resuscitation (DCR) seeks to combat metabolic decompensation of the severely injured trauma patient by battling on three major fronts: Permissive Hypotension, Hemostatic Resuscitation, and Damage Control Surgery (DCS). The aim of this article is to perform a review of the history of DCR/DCS and to propose a new paradigm that has emerged from the recent advancements in endovascular technology: The Resuscitative Balloon Occlusion of the Aorta (REBOA). Thanks to the advances in technology, a bridge has been created between Pre-hospital Management and the Control of Bleeding described in Stage I of DCS which is the inclusion and placement of a REBOA. We have been able to show that REBOA is not only a tool that aids in the control of hemorrhage, it is also a vital tool in the hemodynamic resuscitation of a severely injured blunt and/or penetrating trauma patient. That is why we propose a new paradigm “The Fourth Pillar”: Permissive Hypotension, Hemostatic Resuscitation, Damage Control Surgery and REBOA.
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Affiliation(s)
- Carlos A Ordoñez
- Fundación Valle del Lili. Division of Trauma and Acute Care Surgery, Department of Surgery. Cali, Colombia.,Universidad del Valle, Facultad de Salud, Escuela de Medicina. Cali, Colombia.,Universidad Icesi, Cali, Colombia
| | - Michael W Parra
- Broward General Level I Trauma Center, Department of Trauma Critical Care, Fort Lauderdale, FL - USA
| | - José Julián Serna
- Fundación Valle del Lili. Division of Trauma and Acute Care Surgery, Department of Surgery. Cali, Colombia.,Universidad del Valle, Facultad de Salud, Escuela de Medicina. Cali, Colombia.,Universidad Icesi, Cali, Colombia.,Hospital Universitario del Valle, Division of Trauma and Acute Care Surgery, Department of Surgery. Cali, Colombia
| | - Fernando Rodríguez-Holguin
- Fundación Valle del Lili. Division of Trauma and Acute Care Surgery, Department of Surgery. Cali, Colombia
| | - Alberto García
- Fundación Valle del Lili. Division of Trauma and Acute Care Surgery, Department of Surgery. Cali, Colombia.,Universidad del Valle, Facultad de Salud, Escuela de Medicina. Cali, Colombia.,Universidad Icesi, Cali, Colombia
| | - Alexander Salcedo
- Fundación Valle del Lili. Division of Trauma and Acute Care Surgery, Department of Surgery. Cali, Colombia.,Universidad del Valle, Facultad de Salud, Escuela de Medicina. Cali, Colombia.,Universidad Icesi, Cali, Colombia
| | - Yaset Caicedo
- Fundación Valle del Lili, Centro de Investigaciones Clínicas (CIC), Cali, Colombia
| | - Natalia Padilla
- Fundación Valle del Lili, Centro de Investigaciones Clínicas (CIC), Cali, Colombia
| | - Luis Fernando Pino
- Universidad del Valle, Facultad de Salud, Escuela de Medicina. Cali, Colombia.,Hospital Universitario del Valle, Division of Trauma and Acute Care Surgery, Department of Surgery. Cali, Colombia
| | - Adolfo González Hadad
- Universidad del Valle, Facultad de Salud, Escuela de Medicina. Cali, Colombia.,Hospital Universitario del Valle, Division of Trauma and Acute Care Surgery, Department of Surgery. Cali, Colombia.,Centro Médico Imbanaco, Cali, Colombia
| | - Mario Alain Herrera
- Universidad del Valle, Facultad de Salud, Escuela de Medicina. Cali, Colombia.,Hospital Universitario del Valle, Division of Trauma and Acute Care Surgery, Department of Surgery. Cali, Colombia
| | - Mauricio Millán
- Universidad Icesi, Cali, Colombia.,Fundación Valle del Lili, Division of Transplant Surgery, Department of Surgery, Cali, Colombia
| | - Laureano Quintero-Barrera
- Universidad del Valle, Facultad de Salud, Escuela de Medicina. Cali, Colombia.,Centro Médico Imbanaco, Cali, Colombia
| | - Fabian Hernández-Medina
- Universidad del Valle, Facultad de Salud, Escuela de Medicina. Cali, Colombia.,Hospital Universitario del Valle, Division of Trauma and Acute Care Surgery, Department of Surgery. Cali, Colombia
| | - Ricardo Ferrada
- Universidad del Valle, Facultad de Salud, Escuela de Medicina. Cali, Colombia.,Centro Médico Imbanaco, Cali, Colombia
| | - Megan Brenner
- University of California, Department of Surgery Riverside University Health Systems . Riverside , CA , USA
| | - Todd Rasmussen
- Uniformed Services University, F. Edward Hebert School of Medicine, Department of Surgery, Bethesda, Maryland. USA
| | - Thomas Scalea
- University of Maryland, Department of Surgery, School of Medicine, Baltimore, MD USA
| | - Rao Ivatury
- Professor Emeritus Virginia Commonwealth University, Richmond, VA, USA
| | - John B Holcomb
- University of Alabama Center for Injury Science, Department of Surgery, Birmingham. AL, USA
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Baker JE, Martin GE, Katsaros G, Lewis HV, Wakefield CJ, Josephs SA, Nomellini V, Makley AT, Goodman MD. Variability of fluid administration during exploratory laparotomy for abdominal trauma. Trauma Surg Acute Care Open 2018; 3:e000240. [PMID: 30623027 PMCID: PMC6307576 DOI: 10.1136/tsaco-2018-000240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2018] [Revised: 10/16/2018] [Accepted: 10/30/2018] [Indexed: 11/30/2022] Open
Abstract
Background Approximately 8% of traumatically injured patients require transfusion with packed red blood cells (pRBC) and only 1% to 2% require massive transfusion. Intraoperative massive transfusion was defined as requiring greater than 5 units (u) of pRBC in 4 hours. Despite the majority of patients not requiring transfusion, the appropriate amount and type of crystalloid administered during the era of damage control resuscitation have not been analyzed. We sought to determine the types of crystalloid used during trauma laparotomies and the potential effects on resuscitation. Methods Patients who underwent laparotomy after abdominal trauma from January 2014 to December 2016 at the University of Cincinnati Medical Center were identified. Patients were grouped based on requiring 0u, 1u to 4u, and ≥5u pRBC during intraoperative resuscitation. Demographic, physiologic, pharmacologic, operative, and postoperative data were collected. Statistical analysis was performed with Kruskal-Wallis test and Pearson’s correlation coefficient. Results Lactated Ringer’s (LR) solution was the most used crystalloid type received in the 0u and 1u to 4u pRBC cohorts, whereas normal saline (NS) was the most common in the ≥5u pRBC cohort. Most patients received two types of crystalloid intraoperatively. NS and LR were most frequently the first crystalloids administered, with Normosol infusion occurring later. The amount of crystalloid received correlated with operative length, but did not correlate with the estimated blood loss. Neither the type of crystalloid administered nor the anesthesia provider type was associated with changes in postoperative resuscitation parameters or electrolyte concentrations. Discussion There is a wide variation in the amount and types of crystalloids administered during exploratory laparotomy for trauma. Interestingly, the amount or type of crystalloid given did not affect resuscitation parameters regardless of blood product requirement. Level of evidence Level IV.
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Affiliation(s)
- Jennifer E Baker
- Divisions of Trauma and Research, Section of General Surgery, Department of Surgery, University of Cincinnati, Cincinnati, Ohio, USA
| | - Grace E Martin
- Divisions of Trauma and Research, Section of General Surgery, Department of Surgery, University of Cincinnati, Cincinnati, Ohio, USA
| | - Gianna Katsaros
- Divisions of Trauma and Research, Section of General Surgery, Department of Surgery, University of Cincinnati, Cincinnati, Ohio, USA
| | - Hannah V Lewis
- Divisions of Trauma and Research, Section of General Surgery, Department of Surgery, University of Cincinnati, Cincinnati, Ohio, USA
| | - Connor J Wakefield
- Divisions of Trauma and Research, Section of General Surgery, Department of Surgery, University of Cincinnati, Cincinnati, Ohio, USA
| | - Sean A Josephs
- Department of Anesthesia, University of Cincinnati, Cincinnati, Ohio, USA
| | - Vanessa Nomellini
- Divisions of Trauma and Research, Section of General Surgery, Department of Surgery, University of Cincinnati, Cincinnati, Ohio, USA
| | - Amy T Makley
- Divisions of Trauma and Research, Section of General Surgery, Department of Surgery, University of Cincinnati, Cincinnati, Ohio, USA
| | - Michael D Goodman
- Divisions of Trauma and Research, Section of General Surgery, Department of Surgery, University of Cincinnati, Cincinnati, Ohio, USA
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Jones DG, Nantais J, Rezende-Neto JB, Yazdani S, Vegas P, Rizoli S. Crystalloid resuscitation in trauma patients: deleterious effect of 5L or more in the first 24h. BMC Surg 2018; 18:93. [PMID: 30400852 PMCID: PMC6219036 DOI: 10.1186/s12893-018-0427-y] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2017] [Accepted: 10/22/2018] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Over-aggressive intravenous fluid therapy with crystalloids has adverse effects in trauma patients. We assessed the role of large-volume (≥5l) administration of crystalloids within 24h of injury as an independent risk-factor for mortality, in-hospital complications, and prolonged mechanical ventilation. METHODS A retrospective cohort analysis of adult trauma patients admitted to a level 1-trauma center between December 2011 and December 2012. Patient demographics, clinical and laboratory values, and total resuscitation fluid administered within the first 24h of injury were obtained. Outcomes included mortality, in-hospital complications and ventilator-days. Multivariable logistic regression and Poisson regression analyses were performed to investigate any association between the administration of ≥5L crystalloids with the aforementioned outcomes while controlling for selected clinical variables. RESULTS A total of 970 patients were included in the analysis. 264 (27%) received ≥5L of crystalloids in the first 24h of injury. 118 (12%) had in-hospital complications and 337 (35%) required mechanical ventilation. The median age was 46 years (interquartile range (IQR) 27-65) years and 73% (n = 708) were males. The median injury severity score (ISS) was 17 (IQR 9-25). Overall mortality rate was 7% (n = 67). Multivariable logistic regression analysis showed several variables independently associated with mortality (p < 0.05), including resuscitation with ≥5L crystalloid in the first 24h (adjusted odds ratio (aOR) 2.55), older age (aOR 1.03), higher ISS (aOR 1.09), and lower temperature (aOR 0.68). The variables independently associated with in-hospital complications (p < 0.05) were older age, longer ICU stay, and platelet transfusion within 24h of the injury. Need for mechanical ventilation was more common in patients who received ≥5L crystalloids (RR 2.31) had higher ISS (RR 1.02), developed in-hospital complications (RR 1.91) and had lower presenting temperature (RR 0.87). CONCLUSION Large-volume crystalloid resuscitation is associated with increased mortality and longer time ventilated, but not with in-hospital complications such as pneumonia and sepsis. Based on this data, we recommend judicious use of crystalloids in the resuscitation of trauma patients.
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Affiliation(s)
- D G Jones
- Department of Surgery, University of Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada. .,St. Michael's Hospital Department of Surgery, University of Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.
| | - J Nantais
- Department of Surgery, University of Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.,St. Michael's Hospital Department of Surgery, University of Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada
| | - J B Rezende-Neto
- Department of Surgery, University of Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.,St. Michael's Hospital Department of Surgery, University of Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada
| | - S Yazdani
- St. Michael's Hospital Department of Surgery, University of Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada
| | - P Vegas
- St. Michael's Hospital Department of Surgery, University of Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada
| | - S Rizoli
- Department of Surgery, University of Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.,St. Michael's Hospital Department of Surgery, University of Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada
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Chang P, Weykamp M, Dennahy IS, Williams AM, Bhatti UF, Liu B, Nikolian VC, Li Y, Alam HB. Histone deacetylase inhibitors: Isoform selectivity improves survival in a hemorrhagic shock model. J Trauma Acute Care Surg 2018; 84:795-801. [PMID: 29401190 PMCID: PMC6318805 DOI: 10.1097/ta.0000000000001824] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Hemorrhage is a leading preventable cause of death. Nonselective histone deacetylase inhibitors (HDACIs), such as valproic acid (VPA), have been shown to improve outcomes in hemorrhagic shock (HS). The HDACs can be divided into four functional classes (I, IIa/IIb, III, and IV). Classes I, IIa/IIb, and III have previously been implicated in the pathophysiology of HS. This study aimed to determine which HDAC class, or classes, are responsible for the survival benefit observed with nonselective HDACIs. METHODS Survival study: Sprague-Dawley rats were subjected to lethal HS (50% hemorrhage) and randomized to the following groups (n = 8): (1) no treatment, (2) normal saline vehicle, (3) cyclodextrin vehicle, (4) MS275 (class I HDACI), (5) VPA (class I/IIa HDACI), (6) MC1568 (class IIa HDACI), (7) ACY1083 (class IIb HDACI), and (8) EX527 (class III HDACI). Survival was monitored for 24 hours. Mechanistic study: Sprague-Dawley rats were subjected to sublethal HS (40% hemorrhage) and randomized to the same groups (n = 3), excluding EX527, based on results of the survival study. Tissues were harvested at 3 hours posttreatment, and expression of phosphorylated-AKT, β-catenin, acetylated histones H3 and H4, and acetylated α-tubulin were analyzed in myocardial tissue. RESULTS Survival rate was 12.5% in the untreated group, and did not improve with vehicle or MS275 treatment. EX527 improved survival to 50%, although this did not achieve statistical significance (p = 0.082). However, treatment with VPA, MC1568, and ACY1083 improved survival rates to 87.5%, 75%, and 75%, respectively (p < 0.05). The VPA-induced acetylation of both histones H3 and H4, while MC1568 and ACY1083 increased acetylation of histone H4. ACY1083 also induced acetylation of α-tubulin. All treatment groups, except MS275, increased phosphorylated-AKT, and β-catenin. CONCLUSION Inhibition of HDAC classes IIa or IIb, but not class I, activates prosurvival pathways, which may be responsible for the improved outcomes in rodent models of HS.
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Affiliation(s)
- Panpan Chang
- Department of Neurosurgery, the First Hospital of China Medical University, Shenyang, China
- Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan
| | - Michael Weykamp
- Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan
| | - Isabel S. Dennahy
- Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan
| | - Aaron M. Williams
- Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan
| | - Umar F. Bhatti
- Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan
| | - Baoling Liu
- Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan
| | - Vahagn C. Nikolian
- Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan
| | - Yongqing Li
- Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan
| | - Hasan B. Alam
- Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan
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6
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Nikolian VC, Pan B, Mesar T, Dennahy IS, Georgoff PE, Duan X, Liu B, Wu X, Duggan MJ, Alam HB, Li Y. Lung Protective Effects of Low-Volume Resuscitation and Pharmacologic Treatment of Swine Subjected to Polytrauma and Hemorrhagic Shock. Inflammation 2018; 40:1264-1274. [PMID: 28493077 DOI: 10.1007/s10753-017-0569-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Hemorrhage is a common cause of death in the battlefield. Valproic acid (VPA) has been associated with improved outcomes in multiple models of trauma, when combined with isotonic fluid resuscitation. However, isotonic fluid administered in this setting is logistically impractical and may be associated with complications. In this study, we sought to evaluate the feasibility and immunologic impact of combining VPA treatment with low-volume hypertonic saline (HTS). In vivo: female Yorkshire swine were subjected to hemorrhage (40% total blood volume) and polytrauma (rib fracture and delayed liver injury). Animals were kept in shock for 30 minutes and resuscitated with (1) normal saline (NS, 3× hemorrhaged volume), (2) HTS (7.5% saline, 4 mL/kg), or (3) HTS + VPA (4 mg/kg; 150 mg/kg; n = 3/cohort). After 18 hours of observation, animals were euthanized and the lungs evaluated for acute injury and expression of myeloperoxidase (MPO) and caveolin-1 (Cav-1). In vitro: human umbilical vein endothelial cells (HUVECs) were exposed to anoxic conditions (5% CO2, 95% N2) for 16 hours in (1) normosmotic, (2) hyperosmotic (400 mOsm), or (3) hyperosmotic + VPA (4 mM) media. Immunohistochemistry and Western blots were performed to determine Cav-1 expression. Lungs from VPA-treated animals demonstrated decreased acute injury, MPO expression, and endothelial expression of Cav-1 when compared to lungs from animals resuscitated with NS or HTS alone. Similarly, HUVECs cultured in hyperosmotic media containing VPA demonstrated decreased expression of Cav-1. This study demonstrates that combined treatment with VPA and HTS is a viable strategy in hemorrhagic shock and polytrauma. Attenuation of lung injury following VPA treatment may be related to modulation of the inflammatory response.
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Affiliation(s)
- Vahagn C Nikolian
- Department of Surgery, University of Michigan Health System, NCRC Building 26 Room 363N, 2800 Plymouth Road, Ann Arbor, MI, 48109, USA
| | - Baihong Pan
- Department of Surgery, University of Michigan Health System, NCRC Building 26 Room 363N, 2800 Plymouth Road, Ann Arbor, MI, 48109, USA.,Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Tomaz Mesar
- Division of Trauma, Emergency Surgery and Surgical Critical Care, Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA
| | - Isabel S Dennahy
- Department of Surgery, University of Michigan Health System, NCRC Building 26 Room 363N, 2800 Plymouth Road, Ann Arbor, MI, 48109, USA
| | - Patrick E Georgoff
- Department of Surgery, University of Michigan Health System, NCRC Building 26 Room 363N, 2800 Plymouth Road, Ann Arbor, MI, 48109, USA
| | - Xiuzhen Duan
- Department of Pathology, Loyola University Medical Center, Maywood, IL, USA
| | - Baoling Liu
- Department of Surgery, University of Michigan Health System, NCRC Building 26 Room 363N, 2800 Plymouth Road, Ann Arbor, MI, 48109, USA
| | - Xizi Wu
- Emergency Department, The First Hospital of China Medical University, Shenyang, China
| | - Michael J Duggan
- Division of Trauma, Emergency Surgery and Surgical Critical Care, Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA
| | - Hasan B Alam
- Department of Surgery, University of Michigan Health System, NCRC Building 26 Room 363N, 2800 Plymouth Road, Ann Arbor, MI, 48109, USA
| | - Yongqing Li
- Department of Surgery, University of Michigan Health System, NCRC Building 26 Room 363N, 2800 Plymouth Road, Ann Arbor, MI, 48109, USA.
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Bini R, Chiara O, Cimbanassi S, Olivero G, Trombetta A, Cotogni P. Evaluation of capillary leakage after vasopressin resuscitation in a hemorrhagic shock model. World J Emerg Surg 2018. [PMID: 29515645 PMCID: PMC5836391 DOI: 10.1186/s13017-018-0172-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Background Hemorrhagic shock (HS) is a major threat to patients with trauma and spontaneous bleeding. The aim of the study was to investigate early effects of vasopressin on metabolic and hemodynamic parameters and endothelium permeability by measuring capillary leakage compared to those of other resuscitation strategies in a HS model. Methods Forty-five Sprague-Dawley rats were randomized into five groups: S group (n = 5), sham-operated rats without shock or resuscitation; HS group (n = 10), HS and no resuscitation; RL group (n = 10), HS and resuscitation with Ringer’s lactate (RL); RLB group (n = 10), HS and resuscitation with two-third shed blood plus RL; and vasopressin group (n = 10), HS and resuscitation with RL, followed by continuous infusion of 0.04 U/kg/min vasopressin. The effects of resuscitation on hemodynamic parameters [mean arterial pressure (MAP), superior mesenteric artery blood flow (MBF), and mesenteric vascular resistances (MVR)], arterial blood gases, bicarbonate, base deficit, and lactate levels as well as on capillary leakage in the lung, ileum, and kidney were investigated. Capillary leakage was evaluated with Evans blue dye extravasation. Results In the vasopressin group, the MAP was higher than in the RL and RLB groups (p < 0.001), while MBF was decreased (p < 0.001). MVR were increased only in the vasopressin group (p < 0.001). Capillary leakage was increased in the lungs of the animals in the vasopressin group compared to that in the lungs of animals in the RLB group (p < 0.05); this increase was associated with the lowest partial pressure of oxygen (p < 0.05). Conversely, decreased capillary leakage was observed with vasopressin in the ileum (p < 0.05). Increased capillary leakage was observed in the kidney in the RLB and vasopressin groups (p < 0.05). Lastly, vasopressin use was associated with higher base deficit and lactate levels when compared to the RL and RLB groups (p < 0.001). Conclusion Although vasopressin was proposed as a vasoactive drug for provisional hemodynamic optimization in the early phase of HS resuscitation, the overall findings of this experimental study focus on the possible critical side effects of vasopressin on metabolic parameters and endothelium permeability.
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Affiliation(s)
- Roberto Bini
- 1Department of Surgery, S. Giovanni Bosco Hospital, Turin, Italy
| | - Osvaldo Chiara
- 2Trauma Center and Metropolitan Trauma Network Department, Niguarda Hospital, Milan, Italy
| | - Stefania Cimbanassi
- 2Trauma Center and Metropolitan Trauma Network Department, Niguarda Hospital, Milan, Italy
| | - Giorgio Olivero
- 3Department of Surgical Sciences, S. Giovanni Battista Hospital, University of Turin, Turin, Italy
| | | | - Paolo Cotogni
- 5Department of Anesthesia and Intensive Care, S. Giovanni Battista Hospital, University of Turin, Via Giovanni Giolitti 9, 10123 Turin, Italy
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8
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Zhao JX, Wang B, You GX, Wang Y, Chen G, Wang Q, Zhang XG, Zhao L, Zhou H, He YZ. Hypertonic Saline Dextran Ameliorates Organ Damage in Beagle Hemorrhagic Shock. PLoS One 2015; 10:e0136012. [PMID: 26317867 PMCID: PMC4552817 DOI: 10.1371/journal.pone.0136012] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2015] [Accepted: 07/30/2015] [Indexed: 11/18/2022] Open
Abstract
OBJECTIVE The goal of this study was to investigate the effect of hypertonic saline with 6% Dextran-70 (HSD) resuscitation on organ damage and the resuscitation efficiency of the combination of HSD and lactated ringers (LR) in a model of hemorrhage shock in dogs. METHODS Beagles were bled to hold their mean arterial pressure (MAP) at 50 ± 5 mmHg for 1 h. After hemorrhage, beagles were divided into three groups (n = 7) to receive pre-hospital resuscitation for 1 h (R1): HSD (4 ml/kg), LR (40 ml/kg), and HSD+LR (a combination of 4 ml/kg HSD and 40 ml/kg LR). Next, LR was transfused into all groups as in-hospital resuscitation (R2). After two hours of observation (R3), autologous blood was transfused. Hemodynamic responses and systemic oxygenation were measured at predetermined phases. Three days after resuscitation, the animals were sacrificed and tissues including kidney, lung, liver and intestinal were obtained for pathological analysis. RESULTS Although the initial resuscitation with HSD was shown to be faster than LR with regard to an ascending MAP, the HSD group showed a similar hemodynamic performance compared to the LR group throughout the experiment. Compared with the LR group, the systemic oxygenation performance in the HSD group was similar but showed a lower venous-to-arterial CO2 gradient (Pv-aCO2) at R3 (p < 0.05). Additionally, the histology score of the kidneys, lungs and liver were significantly lower in the HSD group than in the LR group (p < 0.05). The HSD+LR group showed a superior hemodynamic response but higher extravascular lung water (EVLW) and lower arterial oxygen tension (PaO2) than the other groups (p < 0.05). The HSD+LR group showed a marginally improved systemic oxygenation performance and lower histology score than other groups. CONCLUSIONS Resuscitation after hemorrhagic shock with a bolus of HSD showed a similar hemodynamic response compared with LR at ten times the volume of HSD, but HSD showed superior efficacy in organ protection. Our findings suggest that resuscitation with the combination of HSD and LR in the pre-hospital setting is an effective treatment.
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Affiliation(s)
- Jing-xiang Zhao
- Institute of Transfusion Medicine, Academy of Military Medical Sciences, No. 27th Taiping Road, HaiDian, Beijing, China
| | - Bo Wang
- Institute of Transfusion Medicine, Academy of Military Medical Sciences, No. 27th Taiping Road, HaiDian, Beijing, China
| | - Guo-xing You
- Institute of Transfusion Medicine, Academy of Military Medical Sciences, No. 27th Taiping Road, HaiDian, Beijing, China
| | - Ying Wang
- Institute of Transfusion Medicine, Academy of Military Medical Sciences, No. 27th Taiping Road, HaiDian, Beijing, China
| | - Gan Chen
- Institute of Transfusion Medicine, Academy of Military Medical Sciences, No. 27th Taiping Road, HaiDian, Beijing, China
| | - Quan Wang
- Institute of Transfusion Medicine, Academy of Military Medical Sciences, No. 27th Taiping Road, HaiDian, Beijing, China
| | - Xi-gang Zhang
- Emergency department, Chinese People’s Liberation Army 307 hospital, No. 8th Dongda Street, Fengtai, Beijing, China
| | - Lian Zhao
- Institute of Transfusion Medicine, Academy of Military Medical Sciences, No. 27th Taiping Road, HaiDian, Beijing, China
| | - Hong Zhou
- Institute of Transfusion Medicine, Academy of Military Medical Sciences, No. 27th Taiping Road, HaiDian, Beijing, China
| | - Yue-zhong He
- Science and Technology department, Academy of Military Medical Sciences, No. 27th Taiping Road, HaiDian, Beijing, China
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9
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Mattox KL. The ebb and flow of fluid (as in resuscitation). Eur J Trauma Emerg Surg 2014; 41:119-27. [PMID: 26038255 DOI: 10.1007/s00068-014-0437-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2014] [Accepted: 07/08/2014] [Indexed: 12/28/2022]
Abstract
Since the early 1960's "resuscitation" following major trauma involved use of replacement crystalloid fluid/estimated blood loss in volumes of 3/1, in the ambulance, emergency room, operating room and surgical intensive care unit. During the past 20 years, MAJOR paradigm shifts have occurred in this concept. As a result hypotensive resuscitation with a view towards restriction of crystalloid, and prevention of complications has occurred. Improved results in both civilian and military environments have been reported. As a result there is new focus on trauma surgical involvement in all aspects of trauma patient management, focus on early aggressive surgical approaches (which may or may not involve an operation), and movement from crystalloid to blood, plasma, and platelet replacement therapy.
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Affiliation(s)
- K L Mattox
- Baylor College of Medicine, Ben Taub General Hospital, One Baylor Plaza, Houston, TX, USA,
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10
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Shields DW, Crowley TP. Current concepts, which effect outcome following major hemorrhage. J Emerg Trauma Shock 2014; 7:20-4. [PMID: 24550625 PMCID: PMC3912645 DOI: 10.4103/0974-2700.125634] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2013] [Accepted: 05/27/2013] [Indexed: 01/20/2023] Open
Abstract
There are a multitude of factors, which effect outcome following major trauma. The recent conflict in the middle-east has advanced our knowledge and developed clinical practice, here within the UK. This article reviews the current and emerging concepts, which effect the outcome of patients sustaining major hemorrage in trauma.
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Affiliation(s)
- David W Shields
- Department of Trauma and Orthopaedic Surgery, Royal Victoria Infirmary, Newcastle Upon Tyne, NE1 4LP, England, UK
| | - Timothy P Crowley
- Department of Trauma and Orthopaedic Surgery, Royal Victoria Infirmary, Newcastle Upon Tyne, NE1 4LP, England, UK
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11
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Cherian A, Udupi BP. Acute coagulopathy of trauma: Mechanism, monitoring, management. World J Anesthesiol 2014; 3:111-118. [DOI: 10.5313/wja.v3.i1.111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2013] [Revised: 01/14/2014] [Accepted: 02/20/2014] [Indexed: 02/06/2023] Open
Abstract
Coagulopathy is a well-known consequence of trauma and is the most common cause of mortality in the young. However, its cause and management is still controversial. A new concept in the understanding of coagulopathy in trauma is the occurrence of Acute coagulopathy of trauma (ACoT). ACoT is associated with hypo perfusion and tissue trauma as seen in massive injury. The incidence of coagulopathy increases with injury scores and is associated with higher number of ventilator days, higher morbidity and mortality. The process of coagulation is better described by the cell based model with a central role for platelets rather than the older plasma based model. This shift in our understanding supports the theory that ACoT results from the endothelial release of thrombomodulin and activated protein C in the presence of hypoperfusion. This in turn leads on to a hyperfibrinolytic and hypocoagulable state. Viscoelastic hemostatic assays are replacing the older tests like prothrombin time in the assessment of coagulopathy. These tests are accurate, determine the need for transfusion and can be performed at the point of care. Damage control resuscitation includes newer concepts like permissive hypotension, increased use of plasma as a part of massive transfusion protocols and damage control surgery.
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12
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Abstract
Damage control resuscitation (DCR) represents the natural evolution of the initial concept of damage control surgery. It currently includes early blood product transfusion, immediate arrest and/or temporization of ongoing hemorrhage (i.e., temporary intravascular shunts and/or balloon tamponade) as well as restoration of blood volume and physiologic/hematologic stability. As a result, DCR addresses the early coagulopathy of trauma, avoids massive crystalloid resuscitation and leaves the peritoneal cavity open when a patient approaches physiologic exhaustion without improvement. This concept also applies to severe injuries within anatomical transition zones as well as extremities. This review will discuss each of these concepts in detail.
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Affiliation(s)
- Chad G Ball
- From the University of Calgary and Foothills Medical Centre, Calgary, Alta
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13
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Mutafchiyski VM, Popivanov GI, Kjossev KC. Medical aspects of terrorist bombings - a focus on DCS and DCR. Mil Med Res 2014; 1:13. [PMID: 25722871 PMCID: PMC4340108 DOI: 10.1186/2054-9369-1-13] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2014] [Accepted: 06/01/2014] [Indexed: 11/10/2022] Open
Abstract
Although terrorist bombings have tormented the world for a long time, currently they have reached unprecedented levels and become a continuous threat without borders, race or age. Almost all of them are caused by improvised explosive devices. The unpredictability of the terrorist bombings, leading to simultaneous generation of a large number of casualties and severe "multidimensional" blast trauma require a constant vigilance and preparedness of every hospital worldwide. Approximately 1-2.6% of all trauma patients and 7% of the combat casualties require a massive blood transfusion. Coagulopathy is presented in 65% of them with mortality exceeding 50%. Damage control resuscitation is a novel approach, developed in the military practice for treatment of this subgroup of trauma patients. The comparison with the conventional approach revealed mortality reduction with 40-74%, lower frequency of abdominal compartment syndrome (8% vs. 16%), sepsis (9% vs. 20%), multiorgan failure (16% vs. 37%) and a significant reduction of resuscitation volumes, both crystalloids and blood products. DCS and DCR are promising new approaches, contributing for the mortality reduction among the most severely wounded patients. Despite the lack of consensus about the optimal ratio of the blood products and the possible influence of the survival bias, we think that DCR carries survival benefit and recommend it in trauma patients with exsanguinating bleeding.
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Affiliation(s)
| | - Georgi I Popivanov
- Clinic of Abdominal Surgery, Military Medical Detachment of Emergency Response, Military Medical Academy, 3 "Georgi Sofiiski" Str., Sofia, Bulgaria
| | - Kirien C Kjossev
- Clinic of Abdominal Surgery, Military Medical Academy, Sofia, Bulgaria
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14
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Sharma P, Benford B, Karaian JE, Keneally R. Effects of volume and composition of the resuscitative fluids in the treatment of hemorrhagic shock. J Emerg Trauma Shock 2012; 5:309-15. [PMID: 23248499 PMCID: PMC3519043 DOI: 10.4103/0974-2700.102372] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2012] [Accepted: 04/19/2012] [Indexed: 11/19/2022] Open
Abstract
Objectives: To evaluate the effectiveness of normal saline, hypertonic saline, and Ringer's lactate solution followed by blood infusion in ameliorating the physiological, biochemical, and organ functions following hemorrhagic shock (HS) in rats. Materials and Methods: Anesthetized, male Sprague-Dawley rats underwent computer-controlled HS, and were randomly divided into five groups consisting of (1) sham, (2) HS without resuscitation, (3) resuscitation with normal saline, (4) resuscitation with hypertonic saline, and (5) resuscitation with Ringer's lactate solution. All resuscitated animals were infused with subsequent infusion of shed blood. Animals were continuously monitored for physiological, hemodynamic, biochemical parameters, and organ dysfunctions. Results: Non-resuscitated animals were unable to survive due to hypotension, poor oxygen metabolism, and lactic acidosis. Although these HS related parameters were corrected by all the fluids used in this study, additional blood infusion was more effective than fluid resuscitation alone. Also, hypertonic saline was more effective than Ringer's lactate solution, and normal saline was the least effective in preserving the liver and kidney functions and muscle damage. Conclusions: All crystalloid fluids were significantly more effective in reversing the HS outcome when used with blood infusion, but hypertonic salinewith blood was more effective in preventing the organ damage than Lactated Ringers solutions or normal saline in the treatment of HS.
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Affiliation(s)
- Pushpa Sharma
- Department of Anesthesiology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
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15
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Shere-Wolfe RF, Galvagno SM, Grissom TE. Critical care considerations in the management of the trauma patient following initial resuscitation. Scand J Trauma Resusc Emerg Med 2012; 20:68. [PMID: 22989116 PMCID: PMC3566961 DOI: 10.1186/1757-7241-20-68] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2012] [Accepted: 08/28/2012] [Indexed: 12/20/2022] Open
Abstract
Background Care of the polytrauma patient does not end in the operating room or resuscitation bay. The patient presenting to the intensive care unit following initial resuscitation and damage control surgery may be far from stable with ongoing hemorrhage, resuscitation needs, and injuries still requiring definitive repair. The intensive care physician must understand the respiratory, cardiovascular, metabolic, and immunologic consequences of trauma resuscitation and massive transfusion in order to evaluate and adjust the ongoing resuscitative needs of the patient and address potential complications. In this review, we address ongoing resuscitation in the intensive care unit along with potential complications in the trauma patient after initial resuscitation. Complications such as abdominal compartment syndrome, transfusion related patterns of acute lung injury and metabolic consequences subsequent to post-trauma resuscitation are presented. Methods A non-systematic literature search was conducted using PubMed and the Cochrane Database of Systematic Reviews up to May 2012. Results and conclusion Polytrauma patients with severe shock from hemorrhage and massive tissue injury present major challenges for management and resuscitation in the intensive care setting. Many of the current recommendations for “damage control resuscitation” including the use of fixed ratios in the treatment of trauma induced coagulopathy remain controversial. A lack of large, randomized, controlled trials leaves most recommendations at the level of consensus, expert opinion. Ongoing trials and improvements in monitoring and resuscitation technologies will further influence how we manage these complex and challenging patients.
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Affiliation(s)
- Roger F Shere-Wolfe
- University of Maryland School of Medicine, R Adams Cowley Shock Trauma Center, 22 S. Greene St, Ste. T1R77, Baltimore, MD 21201, USA.
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16
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Affiliation(s)
- Hasan B Alam
- Harvard Medical School, Division of Trauma, Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital, Boston, Massachusetts, USA
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17
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The immunomodulatory effects of albumin in vitro and in vivo. Adv Pharmacol Sci 2011; 2011:691928. [PMID: 21603190 PMCID: PMC3096151 DOI: 10.1155/2011/691928] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2010] [Revised: 02/17/2011] [Accepted: 02/23/2011] [Indexed: 12/18/2022] Open
Abstract
Albumin appears to have proinflammatory effects in vitro. We hypothesized that albumin would induce a state of tolerance to subsequent administration of lipopolysaccharide (LPS) in vitro and in vivo. RAW264.7 and primary peritoneal macrophages were treated with increasing doses of bovine serum albumin (BSA) and harvested for NF-κB luciferase reporter assay or TNF-α ELISA. In separate experiments, RAW264.7 cells were preconditioned with 1 mg/mL BSA for 18 h prior to LPS (10 μg/mL) treatment and harvested for NF-κB luciferase reporter assay or TNF-α ELISA. Finally, C57Bl/6 mice were preconditioned with albumin via intraperitoneal administration 18 h prior to a lethal dose of LPS (60 mg/kg body wt). Blood was collected at 6 h after LPS administration for TNF-α ELISA. Albumin produced a dose-dependent and TLR-4-dependent increase in NF-κB activation and TNF-α gene expression in vitro. Albumin preconditioning abrogated the LPS-mediated increase in NF-κB activation and TNF-α gene expression in vitro and in vivo. The clinical significance of these findings remains to be elucidated.
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18
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Abstract
Shock, regardless of etiology is characterized by decreased delivery of oxygen and nutrients to the tissues and our interventions are directed towards reversing the cellular ischemia and preventing its consequences. The treatment strategies that are most effective in achieving this goal obviously depend upon the different types of shock (hemorrhagic, septic, neurogenic and cardiogenic). This brief review focuses on the two leading etiologies of shock in the surgical patients: bleeding and sepsis, and addresses a number of new developments that have profoundly altered the treatment paradigms. The emphasis here is on new research that has dramatically altered our treatment strategies rather than the basic pathophysiology of shock.
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Affiliation(s)
- Hasan B Alam
- Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
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19
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Abstract
In recent years a new understanding of trauma-associated hemorrhaging and trauma-induced coagulopathy has been achieved. This coagulopathy is multifactorial with the predominant mechanisms being tissue trauma, shock and hypoperfusion which can lead to hyperfibrinolysis by activation of the endothelium. Routinely tested coagulation parameters, such as prothrombin time and partial thromboplastin time, are frequently employed for decision making but remain problematic as they do not give any information on clot stability, lysis or platelet function. Thrombelastometry seems to be a useful alternative. A pro-active anticipatory approach is required for a successful outcome to be achieved as rescue correction is more difficult than prevention. While the pathophysiological conception of causal relationship of the mentioned therapeutic options is conclusive, an evidence-based validation by randomized controlled studies is mostly lacking. The emergency and anesthesiological concept of damage control resuscitation consists of limiting volume therapy with crystalloids and colloids to reach a mean arterial pressure > or =65 mmHg (higher for head injuries), active (re-)warming management, the prevention of a pH< or =7.2 and a base excess (BE) < or =-6 mmol/l. The early and sufficient application of hemostatic drugs is essential. Because erythrocytes play a substantial role in the coagulation process, hemoglobin (Hb) values of around 6. 2 mmol/l (10 g/dl) and/or a hematocrit of 30% should be strived for when massive non-arrested hemorrhaging occurs. After severe multiple trauma a fibrinogen deficit develops and must be adequately compensated. If coagulation therapy is carried out using fresh frozen plasma sufficient quantities (20-30 ml/kgBW) must be administered to correspondingly raise the coagulation factors. Prothrombin complex concentrates can be helpful to optimize thrombin generation during severe hemorrhaging. Because hyperfibrinolysis occurs more often than previously assumed during severe trauma, an anti-fibrinolytic therapy should be used especially for patients with an instable circulation. The platelet count should not go below 100,000/microl when hemorrhaging occurs after multiple trauma. For thrombocytopathic patients with diffuse bleeding desmopressin (DDAVP) is a therapeutic option and the "off label" use of recombinant activated factor VIIa (rFVIIa) remains an option for individual situations with stringent indications and when the above named measures to optimize the coagulation situation have been taken.
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20
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Burns, inflammation, and intestinal injury: protective effects of an anti-inflammatory resuscitation strategy. ACTA ACUST UNITED AC 2010; 67:1162-8. [PMID: 20009662 DOI: 10.1097/ta.0b013e3181ba3577] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
BACKGROUND Intestinal barrier breakdown after severe burn can lead to intestinal inflammation, which may act as the source of the systemic inflammatory response. In vitro intestinal cell studies have shown that mitogen-activated protein kinase (MAPK) signaling is an important modulator of intestinal inflammation. We have previously observed that pentoxifylline (PTX) attenuates burn-induced intestinal permeability and tight junction breakdown. We hypothesized that PTX would limit intestinal barrier breakdown and attenuate inflammatory signaling via the MAPK pathway. METHODS Male balb/c mice underwent 30% total body surface area full-thickness steam burn. Immediately after burn, animals received an intraperitoneal injection of PTX (12.5 mg/kg) in normal saline or normal saline alone. In vivo intestinal permeability to 4 kDa fluorescein isothiocyanate-dextran was measured. Intestinal extracts were obtained to measure interleukin-6 by enzyme-linked immunosorbent assay, and phosphorylated p38 MAPK, p38 MAPK, phosphorylated extracellular signal-related kinase (1/2) (ERK (1/2)), and ERK (1/2) by immunoblotting. Acute lung injury was assessed by histology at 24 hours after burn. RESULTS Administration of PTX immediately after injury attenuated burn-induced intestinal permeability. PTX also decreased the burn-induced phosphorylation of p38 MAPK and decreased phosphorylation of ERK (1/2) at 2 hours and 24 hours after injury. Animals given PTX had decreased intestinal interleukin-6 levels. A single dose of PTX also decreased histologic lung injury at 24 hours after burn. CONCLUSION PTX attenuates burn-induced intestinal permeability and subsequent intestinal inflammation. Use of PTX after burn was also associated with decreased acute lung injury. Because of its compelling anti-inflammatory effects, PTX may be an ideal candidate for use as an immunomodulatory adjunct to resuscitation fluid.
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21
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Quigley A, Tan AA, Hoane MR. The effects of hypertonic saline and nicotinamide on sensorimotor and cognitive function following cortical contusion injury in the rat. Brain Res 2009; 1304:138-48. [PMID: 19781534 PMCID: PMC2784246 DOI: 10.1016/j.brainres.2009.09.062] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2009] [Revised: 09/15/2009] [Accepted: 09/16/2009] [Indexed: 11/30/2022]
Abstract
Hypertonic saline (HTS) is an accepted treatment for traumatic brain injury (TBI). However, the behavioral and cognitive consequences following HTS administration have not thoroughly been examined. Recent preclinical evidence has suggested that nicotinamide (NAM) is beneficial for recovery of function following TBI. The current study compared the behavioral and cognitive consequences of HTS and NAM as competitive therapeutic agents for the treatment of TBI. Following controlled cortical impact (CCI), bolus administrations of NAM (500 mg/kg), 7.5% HTS, or 0.9% saline Vehicle (1.0 mL/kg) were given at 2, 24, and 48 h post-CCI. Behavioral results revealed that animals treated with NAM and HTS showed significant improvements in beam walk and locomotor placing compared to the Vehicle group. The Morris water maze (MWM) retrograde amnesia test was conducted on day 12 post-CCI and showed that all groups had significant retention of memory compared to injured, Vehicle-treated animals. Working memory was also assessed on days 8-20 using the MWM. The NAM and Vehicle groups quickly acquired the task; however, HTS animals showed no acquisition of this task. Histological examinations revealed that the HTS-treated animals lost significantly more cortical tissue than either the NAM or Vehicle-treated animals. HTS-treated animals showed a greater loss of hippocampal tissue compared to the other groups. In general, NAM showed a faster rate of recovery than HTS without this associated tissue loss. The results of this study reiterate the strengths of NAM following injury and show concerns with bolus administrations of HTS due to the differential effects on cognitive performance and apparent tissue loss.
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22
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Exadaktylos AK, Alam HB. [The war on (too many) fluids. New horizons in combat medicine]. Unfallchirurg 2009; 112:670, 672-3. [PMID: 19603217 DOI: 10.1007/s00113-008-1562-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
In the coming years, our approach to the bleeding patient will have to change radically. The inevitable knowledge from the wars in Iraq and Afghanistan permits the prediction that conventional crystalloids will sooner or later disappear from volume replacement therapy. The dogma that fluids must always be given will be abandoned, to be replaced by the practice of careful and goal-directed resuscitation. In the near future, we would rely on designer fluids and sophisticated pharmacological agents to deliver personalized resuscitation based upon the specific needs of the individual patient.
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Affiliation(s)
- A K Exadaktylos
- Department of Academic Emergency Medicine, Inselspital, University of Bern, 3010 Bern, Schweiz.
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23
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Azoubel G, Nascimento B, Ferri M, Rizoli S. Operating room use of hypertonic solutions: a clinical review. Clinics (Sao Paulo) 2008; 63:833-40. [PMID: 19061009 PMCID: PMC2664287 DOI: 10.1590/s1807-59322008000600021] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2008] [Accepted: 08/04/2008] [Indexed: 11/22/2022] Open
Abstract
Hyperosmotic-hyperoncotic solutions have been widely used during prehospital care of trauma patients and have shown positive hemodynamic effects. Recently, there has been a growing interest in intra-operative use of hypertonic solutions. We reviewed 30 clinical studies on the use of hypertonic saline solutions during surgeries, with the majority being cardiac surgeries. Reduced positive fluid balance, increased cardiac index, and decreased systemic vascular resistance were the main beneficial effects of using hypertonic solutions in this population. Well-designed clinical trials are highly needed, particularly in aortic aneurysm repair surgeries, where hypertonic solutions have shown many beneficial effects. Examining the immunomodulatory effects of hypertonic solutions should also be a priority in future studies.
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Affiliation(s)
- Gustavo Azoubel
- Department of Surgery, University of Toronto - Toronto, Canada
| | - Bartolomeu Nascimento
- Department of Trauma and Critical Care, Sunnybrook Health Sciences Centre - Toronto, Ontario, Canada.
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, Tel.: 416 5194041
| | - Mauricio Ferri
- Department of Trauma and Critical Care, Sunnybrook Health Sciences Centre - Toronto, Ontario, Canada.
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, Tel.: 416 5194041
| | - Sandro Rizoli
- Department of Surgery, University of Toronto - Toronto, Canada
- Department of Trauma and Critical Care, Sunnybrook Health Sciences Centre - Toronto, Ontario, Canada.
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, Tel.: 416 5194041
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Horton JW, Maass DL, White DJ. Hypertonic saline dextran after burn injury decreases inflammatory cytokine responses to subsequent pneumonia-related sepsis. Am J Physiol Heart Circ Physiol 2005; 290:H1642-50. [PMID: 16299261 PMCID: PMC1550345 DOI: 10.1152/ajpheart.00586.2005] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
The present study examined the hypothesis that hypertonic saline dextran (HSD), given after an initial insult, attenuates exaggerated inflammation that occurs with a second insult. Adult rats (n = 15 per group) were divided into groups 1 (sham burn), 2 [40% total body surface area burn + 4 ml/kg isotonic saline (IS) + 4 ml.kg(-1).% burn(-1) lactated Ringer solution (LR)], and 3 (burn + 4 ml/kg HSD + LR), all studied 24 h after burns. Groups 4 (sham burn), 5 (burn + IS + LR), and 6 (burns + HSD + LR) received intratracheal (IT) vehicle 7 days after burns; groups 7 (burn + IS + LR) and 8 (burn + HSD + LR) received IT Streptococcus pneumoniae (4 x 10(6) colony-forming units) 7 days after burn. Groups 4-8 were studied 8 days after burn and 24 h after IT septic challenge. When compared with sham burn, contractile defects occurred 24 h after burn in IS-treated but not HSD-treated burns. Cardiac inflammatory responses (pg/ml TNF-alpha) were evident with IS (170 +/- 10) but not HSD (45 +/- 5) treatment vs. sham treatment (80 +/- 15). Pneumonia-related sepsis 8 days after IS-treated burns (group 7) exacerbated TNF-alpha responses/contractile dysfunction vs. IS-treated burns in the absence of sepsis (P < 0.05). Sepsis that occurred after HSD-treated burns (group 8) had less myocyte TNF-alpha secretion/better contractile function than IS-treated burns given septic challenge (group 7, P < 0.05). We conclude that an initial burn injury exacerbates myocardial inflammation/dysfunction occurring with a second insult; giving HSD after the initial insult attenuates myocardial inflammation/dysfunction associated with a second hit, suggesting that HSD reduces postinjury risk for infectious complications.
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Affiliation(s)
- Jureta W Horton
- Dept. of Surgery, UT Southwestern Medical Center, Dallas, TX 75390-9160, USA.
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25
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Kauvar DS, Wade CE. The epidemiology and modern management of traumatic hemorrhage: US and international perspectives. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2005; 9 Suppl 5:S1-9. [PMID: 16221313 PMCID: PMC3226117 DOI: 10.1186/cc3779] [Citation(s) in RCA: 263] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Trauma is a worldwide problem, with severe and wide ranging consequences for individuals and society as a whole. Hemorrhage is a major contributor to the dilemma of traumatic injury and its care. In this article we describe the international epidemiology of traumatic injury, its causes and its consequences, and closely examine the role played by hemorrhage in producing traumatic morbidity and mortality. Emphasis is placed on defining situations in which traditional methods of hemorrhage control often fail. We then outline and discuss modern principles in the management of traumatic hemorrhage and explore developing changes in these areas. We conclude with a discussion of outcome measures for the injured patient within the context of the epidemiology of traumatic injury.
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Affiliation(s)
- David S Kauvar
- United States Army Institute of Surgical Research, Fort Sam Houston, Texas, USA.
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26
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Abstract
Hemorrhagic shock is the leading cause of death in civilian and combat trauma. Effective hemorrhage control and better resuscitation strategies have the potential of saving lives. The Trauma Readiness and Research Institute for Surgery (TRRI-Surg) was established to address the core mission of the Uniformed Services University, "Learning to Care for Those in Harm's Way," by conducting research to improve the outcome of combat casualties. This article highlights the salient achievements of this research effort in the areas of hemorrhage control, resuscitation, design and testing of devices, and some novel concepts such as the use of profound hypothermia. The impact of these basic science research findings on changes in military medical care and outcome of injured soldiers is also described.
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Affiliation(s)
- Hasan B Alam
- Trauma Research and Readiness Institute for Surgery, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799, USA.
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27
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Zakaria ER, Garrison RN, Kawabe T, Harris PD. Direct peritoneal resuscitation from hemorrhagic shock: effect of time delay in therapy initiation. ACTA ACUST UNITED AC 2005; 58:499-506; discussion 506-8. [PMID: 15761343 PMCID: PMC1775035 DOI: 10.1097/01.ta.0000152892.24841.54] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND After conventional resuscitation from hemorrhagic shock, splanchnic microvessels progressively constrict, leading to impairment of blood flow. This occurs despite restoration and maintenance of central hemodynamics. The authors' recent studies have demonstrated that topical and continuous ex vivo exposure of the gut microvasculature to a glucose-based clinical peritoneal dialysis solution (Delflex), as a technique of direct peritoneal resuscitation (DPR), can prevent these postresuscitation events when initiated simultaneously with conventional resuscitation. This study aimed to determine whether DPR applied after conventional resuscitation reverses the established postresuscitation intestinal vasoconstriction and hypoperfusion. METHODS Male Sprague-Dawley rats were bled to 50% of baseline mean arterial pressure and resuscitated intravenously over 30 minutes with the shed blood returned plus two times the shed blood volume of saline. Initiation of ex vivo, topical DPR was delayed to 2 hours (group 1, n = 8), or to 4 hours (group 2, n = 8), respectively, after conventional resuscitation. Intravital microscopy and Doppler velocimetry were used to measure terminal ileal microvascular diameters of inflow A1 and premucosal A3 (proximal pA3, distal dA3) arterioles and blood flow in the A1 arteriole, respectively. Maximum arteriolar dilation capacity was obtained from the topical application, in the tissue bath, of the endothelium-independent nitric oxide-donor sodium nitroprusside (10M). RESULTS Hemorrhagic shock caused a selective vasoconstriction of A1 (-24.1% +/- 2.15%) arterioles from baseline, which was not seen in A3 vessels. This caused A1 blood flow to drop by -68.6% of the prehemorrhage value. Conventional resuscitation restored and maintained hemodynamics in all the animals without additional fluid therapy. In contrast, there was a generalized and progressive postresuscitation vasoconstriction of A1 (-21.7%), pA3 (-18.5%), and dA3 (-18.7%) vessels. The average postresuscitation A1 blood flow was -49.5% of the prehemorrhage value, indicating a persistent postresuscitation hypoperfusion. Direct peritoneal resuscitation reversed the postresuscitation vasoconstriction by 40.9% and enhanced A1 blood flow by 112.9% of the respective postresuscitation values. CONCLUSIONS Delayed DPR reverses the gut postresuscitation vasoconstriction and hypoperfusion regardless of the initiation time. This occurs without adverse effects on hemodynamics. Direct peritoneal resuscitation-mediated enhancement of tissue perfusion results from the local effects from the vasoactive components of the Delflex solution, which are hyperosmolality, lactate buffer anion, and, to a lesser extent, low pH. The molecular mechanism of this vasodilation effect needs further investigation.
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Affiliation(s)
- El Rasheid Zakaria
- Department of Physiology and Biophysics, University of Louisville, Kentucky 40292, USA.
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