1. Hypertonic Saline in the Treatment of Sepsis Hershberger, T. and Nibblett, B. Ross University School of Veterinary Medicine Key Points A dog presenting with septic shock secondary to severe bite injuries may benefited from the administration of hypertonic saline solution. Potential benefits of hypertonic saline include: decrease in endothelial cell edema increased cardiac contractility decreased peripheral vascular resistance significant intravascular volume expansion with a synergistic effect with concurrent colloid administration immunomodulation.. Case Summary A 20kg, 7 year old, castrated male, mixed breed canine presented to Ross University School of Veterinary Medicine teaching hospital for severe dog bite wounds incurred approximately 12 hours earlier. Physical exam findings were as follows: prolonged skin tent, hypothermia, tachypnea, tachycardia, prolonged capillary refill time, poor to absent peripheral pulses, dull mentation, scleral petechiation, and extensive trauma involving 75% of the body, including elbow luxation and mandibular fracture. Shock was suspected to be due to both hypovolemia and sepsis. Preliminary lab work revealed panhypoproteinemia, azotemia, mild non- regenerative anemia, severe panleukopenia with a degenerative left shift, thrombocytopenia, and lactic acidosis. Emergency treatment included a full shock dose of intravenous crystalloids, a Hetastarch bolus, and hypertonic saline to restore circulating blood volume and oncotic pressure. Analgesia and systemic antibiotic therapy was initiated and a Foley urinary catheter placed to monitor urine output. One unit of fresh frozen plasma was administered intravenously to provide further oncotic support when hypotension persisted despite fluid resuscitation efforts. The dog ‘s condition stabilized over the first 24 hours. Attempts to save the left forelimb failed necessitating amputation. He was discharged from the hospital 3 weeks later Discussion Septic shock is a severe form of sepsis that is characterized by organ dysfunction and failure with refractile hypotension 1 and is associated with a poor prognosis. Systemic inflammatory response syndrome (SIRS) = imbalance between pro-inflammatory and anti-inflammatory mediators 2 Inflammatory cells involved: macrophages, neutrophils, endothelium and platelets Widespread vasodilation and increased capillary permeability induce hypotension, peripheral edema and cellular edema Hypercoagulative state: disseminated intravascular coagulation (DIC) with microclots that may lodge in the microvasculature. Hypoxia: tissue injury and organ dysfunction  multiple organ dysfunction syndrome, or MODS 3. “There is literature to support that the use of hypertonic saline may have provided the key to his recovery.” Resources 1.1. "Septic Shock." Merriam-Webster.com. Merriam-Webster, n.d. Web. 3 Sept. 2013.. 2.2. Anas, A. A., W. J. Wiersinga, A. F. De Vos, and T. Van Der Poll. "Recent Insights Into the Pathogenesis of Bacterial Sepsis." The Netherlands Journal of Medicine 68.4 (2010): 147-52. Print. 3.3. Sharp, Claire R. "SIRS, Sepsis, MODS, MOF and More." ISBN: 978-1- 62276-153-1 American College of Veterinary Internal Medicine (ACVIM) Forum 2012. New York: Curran Associates, 2012. 483-86. Print. New Orleans, Louisiana, USA, 30 May - 2 June 2012. 4.4. Oliveira RP, Velasco I, Soriano FG, Friedman G. Clinical review: Hypertonic saline resuscitation in sepsis. Crit Care. 2002 Oct;6(5):418-23. Epub 2002 Aug 6. Review. PubMed PMID: 12398781; PubMed Central PMCID: PMC137320. Conclusions There is literature to support that the use of hypertonic saline in the patient’s initial fluid resuscitation protocol, especially in combination with Hetastarch, may have been the key 4. Hypertonic saline solution (HSS) has been found to mediate many of the problems associated with septic shock by decreasing endothelial cell edema, causing peripheral vasodilation, increasing myocardial contractility, and causing plasma volume expansion. Administration of HSS with colloid like Hetastarch has been shown to increase the volume expansion compared to HSS alone, as well as prolong the duration of the effect. Vasodilation as a benefit seems contradictive, but when combined with volume expansion is helpful in the face of circulating vasoconstricting hormones like epinephrine and angiotensin II. Another significant advantage to using hypertonic saline in our patient is its immunomodulatory effects 4. HSS decreases neutrophil margination, increases T-cell proliferation, and interrupts some cellular signaling pathways resulting in suppression of neutrophil degranulation and superoxide formation. At the cellular level these mechanisms assist in bacterial neutralization, but can also cause significant host tissue damage if allowed to occur unchecked. Hypertonic saline modulates some of the pro-inflammatory stimulation, allowing a better balance in the overall inflammatory reaction and allowed the patient to continue fighting his bacterial infection while minimizing any contribution to unruly systemic inflammation. Perfusion was compromised in our patient due to septic shock/SIRS, and hypovolemia from acute blood loss and dehydration, setting the stage for the development of MODS. His severe lactic acidosis was evidence of significant lack of tissue perfusion. Thrombocytopenia and scleral petechiation alluded to the development of DIC, however additional lab work that could have confirmed the diagnosis, such as coagulation time and fibrin degradation products was not performed. The prognosis for patients in any type of shock is worsened by increased time before stabilization. This is especially true of septic shock as we arecombating the effects of widespread inflammation in addition to inadequate tissue perfusion. Because of the delay in our patient’s arrival at the hospital, his condition was poor and aggressive treatment was indicated to restore circulating blood volume as quickly as possible to prevent further organ dysfunction and hopefully begin to correct any existing organ damage. Given the patient’s status at time of presentation, his treatment was expected to have a negative outcome. However with supportive care he recovered with no obvious long-term detriment other than the left forelimb amputation. What aspects of his treatment were responsible for his dramatic recovery? Acknowledgements Case Clinicians: Susan Porter, Nick Spaccarelli, Rebecca Hall, Christa Gallagher Technical assistance: Paul Orchard Photos: RUSVM VTH Debridement of deep wound over left forelimb elbow.. Left thoracic limb showing severe necrosis. © 2013 Global Education International. All rights reserved.