Linda G. Martin

Serum antibodies against human albumin in critically ill and healthy dogs

OBJECTIVE To characterize the magnitude and duration of the antibody response against human albumin (HA) in critically ill and healthy dogs. DESIGN Cohort and cross-sectional study. ANIMALS Fourteen critically ill dogs that received 25% HA as part of their treatment protocol, 2 healthy dogs with no known previous exposure to HA that received 2 infusions of 25% HA (positive control dogs), and 47 healthy dogs and 21 critically ill dogs with no known exposure to HA (negative control dogs). PROCEDURES An ELISA to detect IgG against HA was developed. Serum samples were obtained from the critically ill dogs prior to infusion of HA, at the time of hospital discharge, and 4 to 6 weeks and 6 months after HA administration. Serum samples were obtained at 2- to 4-week intervals from both positive control dogs for 101 weeks. A single serum sample was obtained from each of the negative control dogs. RESULTS All 14 critically ill dogs developed serum IgG against HA. Peak antibody response was detected 4 to 6 weeks after HA administration. In both positive control dogs, IgG against HA was detected 10 days after HA administration and continued past 97 weeks. The peak antibody response was detected at 3 weeks in 1 dog and at 9 weeks in the other. Five of the 68 (7%) negative control dogs had a positive antibody response. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that dogs developed a pronounced IgG response following exposure to HA and that some dogs with no history of HA administration were positive for anti-HA IgG.

Pituitary-adrenal function in dogs with acute critical illness

OBJECTIVE To evaluate pituitary-adrenal function in critically ill dogs with sepsis, severe trauma, and gastric dilatation-volvulus (GDV). DESIGN Cohort study. ANIMALS 31 ill dogs admitted to an intensive care unit (ICU) at Washington State University or the University of Pennsylvania; all dogs had acute critical illness for < 48 hours prior to admission. PROCEDURES Baseline and ACTH-stimulated serum cortisol concentrations and baseline plasma ACTH concentrations were assayed for each dog within 24 hours after admission to the ICU. The change in cortisol concentrations (Delta-cortisol) was calculated for each dog. Morbidity and mortality data were recorded for each patient. RESULTS Overall, 17 of 31 (55%) acutely critically ill dogs had at least 1 biochemical abnormality suggestive of adrenal gland or pituitary gland insufficiency. Only 1 (3%) dog had an exaggerated response to ACTH stimulation. Dogs with Delta-cortisol < or = 83 nmol/L were 5.7 times as likely to be receiving vasopressors as were dogs with Delta-cortisol > 83 nmol/L. No differences were detected among dogs with sepsis, severe trauma, or GDV with respect to mean baseline and ACTH-stimulated serum cortisol concentrations, Delta-cortisol, and baseline plasma ACTH concentrations. CONCLUSIONS AND CLINICAL RELEVANCE Biochemical abnormalities of the hypothalamic-pituitary-adrenal axis indicative of adrenal gland or pituitary gland insufficiency were common in critically ill dogs, whereas exaggerated responses to ACTH administration were uncommon. Acutely ill dogs with Delta-cortisol < or = 83 nmol/L may be more likely to require vasopressors as part of the treatment plan.

Hypercalcemia and Hypermagnesemia

Hypercalcemia and hypermagnesemia occur infrequently in small animal patients. Specific clinical signs usually do not accompany these electrolyte disorders, and their presence is often recognized only after reviewing serum chemistry profile results. The etiologies, clinical signs, and therapies for each electrolyte disorder are discussed in this article. Treatment of these disorders is aimed at correcting the underlying disease process and enhancing the removal of calcium or magnesium from the body. In severe cases, rescue therapies and resuscitative measures are required to stabilize the patient.

Traumatic coagulopathy‐Part 1: Pathophysiology and diagnosis

Objective To review the current literature in reference to the pathophysiology and diagnostic modalities available for acute traumatic coagulopathy (ATC) in relationship to traumatic hemorrhagic shock. Etiology Posttraumatic hemorrhage is responsible for one of the leading causes of preventable human deaths worldwide. Acute traumatic coagulopathy is an endogenous hypocoagulable condition that has been observed during the immediate (< 1 hour) posttraumatic period. Phenotypically, ATC manifests as a state of systemic hypocoagulability and hyperfibrinolysis. Although different functional mechanisms have been proposed for causing ATC, it is universally thought to be a manifestation of severe tissue injury, shock-induced hypoperfusion, systemic inflammation, and endothelial damage. Excessive activation of the thrombin-thrombomodulin activated Protein C pathway, catecholamine-induced endothelial damage as well as disseminated intravascular coagulation (DIC) with a fibrinolytic phenotype are all hypotheses that have been proposed in attempts to explain the functional mechanism of ATC. Diagnosis An accurate and reliable test remains to be validated for ATC. Traditional coagulation assays (activated partial thromboplastin times and prothrombin times) along with platelet count and fibrinogen concentrations have been used more commonly. Viscoelastic tests (thromboelastography and rotational thromboelastometry) are currently being investigated as a more predictive modality for identifying and guiding therapy for ATC. Therapy Damage control resuscitation and hemostatic resuscitation are gaining favor as the optimal resuscitative strategies for hemorrhagic shock and ATC. Antifibrinolytics may also play a role when hyperfibrinolysis is present. Prognosis Massive hemorrhage accounts for 30–56% of prehospital posttraumatic deaths in people, with coagulopathic hemorrhage remaining one of the major causes of preventable deaths within the first 24 hours posttrauma. Ten to twenty-five percent of human trauma patients experience ATC, which has been shown to prolong hemorrhage, deter resuscitative efforts, promote sepsis, and increase mortality by at least 4-fold. Prognosis in veterinary patients is not currently known.OBJECTIVE To review the current literature in reference to the pathophysiology and diagnostic modalities available for acute traumatic coagulopathy (ATC) in relationship to traumatic hemorrhagic shock. ETIOLOGY Posttraumatic hemorrhage is responsible for one of the leading causes of preventable human deaths worldwide. Acute traumatic coagulopathy is an endogenous hypocoagulable condition that has been observed during the immediate (< 1 hour) posttraumatic period. Phenotypically, ATC manifests as a state of systemic hypocoagulability and hyperfibrinolysis. Although different functional mechanisms have been proposed for causing ATC, it is universally thought to be a manifestation of severe tissue injury, shock-induced hypoperfusion, systemic inflammation, and endothelial damage. Excessive activation of the thrombin-thrombomodulin activated Protein C pathway, catecholamine-induced endothelial damage as well as disseminated intravascular coagulation (DIC) with a fibrinolytic phenotype are all hypotheses that have been proposed in attempts to explain the functional mechanism of ATC. DIAGNOSIS An accurate and reliable test remains to be validated for ATC. Traditional coagulation assays (activated partial thromboplastin times and prothrombin times) along with platelet count and fibrinogen concentrations have been used more commonly. Viscoelastic tests (thromboelastography and rotational thromboelastometry) are currently being investigated as a more predictive modality for identifying and guiding therapy for ATC. THERAPY Damage control resuscitation and hemostatic resuscitation are gaining favor as the optimal resuscitative strategies for hemorrhagic shock and ATC. Antifibrinolytics may also play a role when hyperfibrinolysis is present. PROGNOSIS Massive hemorrhage accounts for 30-56% of prehospital posttraumatic deaths in people, with coagulopathic hemorrhage remaining one of the major causes of preventable deaths within the first 24 hours posttrauma. Ten to twenty-five percent of human trauma patients experience ATC, which has been shown to prolong hemorrhage, deter resuscitative efforts, promote sepsis, and increase mortality by at least 4-fold. Prognosis in veterinary patients is not currently known.

Use of fresh platelet concentrate or lyophilized platelets in thrombocytopenic dogs with clinical signs of hemorrhage: A preliminary trial in 37 dogs

OBJECTIVE To examine the safety and feasibility of using lyophilized platelets (LYO) and fresh platelet concentrate (FRESH) in bleeding thrombocytopenic dogs. DESIGN Preliminary prospective randomized clinical trial. SETTING Two private referral centers and 3 university teaching hospitals. ANIMALS Thirty-seven dogs with a complaint of hemorrhage associated with thrombocytopenia (platelet count <70 × 10(9) /L [70,000/μL], a hematocrit >15%, and that had received neither vincristine nor platelet-containing transfusions within 72 h of enrollment were studied. INTERVENTIONS Animals were randomized to receive LYO or FRESH, dosed according to weight. Physical examination, complete blood counts, and coagulation testing (prothrombin time and activated partial thromboplastin time) were performed at enrollment. Physical examinations were also performed immediately post transfusion, and at 1 and 24 h after transfusion. Complete blood counts were repeated immediately post transfusion and at 24 h. Collected data included bleeding score (BLS), response to transfusion, adverse reactions, hospitalization time, need for additional transfusions, survival to discharge, and 28-d survival. MEASUREMENTS AND MAIN RESULTS Twenty-two dogs received LYO and 15 received FRESH. There was no difference between groups in age, weight, BLS, platelet count, white blood cell count, hematocrit, or presence of melena. There was no difference between groups in transfusion reaction rates, the need for additional transfusions, 24-h BLS, hospitalization time, survival to discharge, or 28-d survival. CONCLUSIONS Transfusion of LYO was feasible and associated with a low transfusion reaction rate in this limited study of thrombocytopenic canine patients presenting with mild-to-severe hemorrhage. LYO were easy to use and provided storage advantages over FRESH. Further study of this product, including examination of efficacy and platelet life span, is warranted.

Critical Illness–Related Corticosteroid Insufficiency in Small Animals

Critical illness-related corticosteroid insufficiency (CIRCI) describes endocrine abnormalities associated with illness. CIRCI is characterized by an inadequate production of cortisol in relation to an increased demand during periods of severe stress, particularly in critical illnesses such as sepsis or septic shock. A hallmark sign of CIRCI is hypotension refractory to fluid resuscitation, requiring vasopressor therapy. Corticosteroid treatment can be indicated in patients with CIRCI. This article reviews the physiology and pathophysiology of the corticosteroid response to critical illness and the incidence, clinical features, diagnosis, and treatment of CIRCI.

Cortisol and aldosterone response to various doses of cosyntropin in healthy cats

OBJECTIVE To determine the lowest dose of cosyntropin on a per body weight basis that would produce maximal cortisol and aldosterone secretion and the ideal timing of blood sample collection after ACTH stimulation in healthy cats. DESIGN Randomized crossover trial. ANIMALS 7 adult sexually intact male purpose-bred cats. PROCEDURES Each cat received saline (0.9% NaCl) solution (control) and 5 doses (125 μg/cat and 10, 5, 2.5, and 1 μg/kg [4.54, 2.27, 1.14, and 0.45 μg/lb]) of cosyntropin IV with a 2-week washout period between treatments. Blood samples were obtained before (baseline) and at 15, 30, 45, 60, 75, and 90 minutes after administration of saline solution or cosyntropin. RESULTS Serum cortisol and aldosterone concentration increased significantly, compared with baseline values, after administration of all cosyntropin doses. Lower doses of cosyntropin resulted in an adrenocortical response equivalent to the traditional dose of 125 μg/cat. The lowest doses of cosyntropin that stimulated a maximal cortisol and aldosterone response were 5 and 2.5 μg/kg, respectively. Lower doses of cosyntropin resulted in a shorter interval between IV administration of cosyntropin and peak serum cortisol and aldosterone concentrations. CONCLUSIONS AND CLINICAL RELEVANCE Low-dose ACTH stimulation testing with IV administration of cosyntropin at 5 μg/kg followed by blood sample collection at 60 to 75 minutes resulted in concurrent peak serum cortisol and aldosterone concentrations that were equivalent to those achieved following administration of cosyntropin at 125 μg/cat, the standard dose currently used.

Validation of a low-dose ACTH stimulation test in healthy adult horses

OBJECTIVE To determine the lowest ACTH dose that would induce a maximum increase in serum cortisol concentration in healthy adult horses and identify the time to peak cortisol concentration. DESIGN Evaluation study. ANIMALS 8 healthy adult horses. PROCEDURES Saline (0.9% NaCl) solution or 1 of 4 doses (0.02, 0.1, 0.25, and 0.5 μg/kg [0.009, 0.045, 0.114, and 0.227 μg/lb]) of cosyntropin (synthetic ACTH) were administered IV (5 treatments/horse). Serum cortisol concentrations were measured before and 30, 60, 90, 120, 180, and 240 minutes after injection of cosyntropin or saline solution; CBCs were performed before and 30, 60, 120, and 240 minutes after injection. RESULTS For all 4 doses, serum cortisol concentration was significantly increased, compared with the baseline value, by 30 minutes after administration of cosyntropin; no significant differences were detected among maximum serum cortisol concentrations obtained in response to administration of doses of 0.1, 0.25, and 0.5 μg/kg. Serum cortisol concentration peaked 30 minutes after administration of cosyntropin at a dose of 0.02 or 0.1 μg/kg, with peak concentrations 1.5 and 1.9 times, respectively, the baseline concentration. Serum cortisol concentration peaked 90 minutes after administration of cosyntropin at a dose of 0.25 or 0.5 μg/kg, with peak concentrations 2.0 and 2.3 times, respectively, the baseline concentration. Cosyntropin administration significantly affected WBC, neutrophil, and eosinophil counts and the neutrophil-to-lymphocyte ratio. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that in healthy horses, administration of cosyntropin at a dose of 0.1 μg/kg resulted in maximum adrenal stimulation, with peak cortisol concentration 30 minutes after cosyntropin administration.

Traumatic coagulopathy--part 2: Resuscitative strategies.

Objective To discuss the current resuscitative strategies for trauma-induced hemorrhagic shock and acute traumatic coagulopathy (ATC). Etiology Hemorrhagic shock can be acutely fatal if not immediately and appropriately treated. The primary tenets of hemorrhagic shock resuscitation are to arrest hemorrhage and restore the effective circulating volume. Large volumes of isotonic crystalloids have been the resuscitative strategy of choice; however, data from experimental animal models and retrospective human analyses now recognize that large-volume fluid resuscitation in uncontrolled hemorrhage may be deleterious. The optimal resuscitative strategy has yet to be defined. In human trauma, implementing damage control resuscitation with damage control surgery for controlling ongoing hemorrhage, acidosis, and hypothermia; managing ATC; and restoring effective circulating volume is emerging as a more optimal resuscitative strategy. With hyperfibrinolysis playing an integral role in the manifestation of ATC, the use of antifibrinolytics (eg, tranexamic acid and aminocaproic acid) may also serve a beneficial role in the early posttraumatic period. Considering the sparse information regarding these resuscitative techniques in veterinary medicine, veterinarians are left with extrapolating information from human trials and experimental animal models. Diagnosis Viscoelastic tests integrated with predictive scoring systems may prove to be the most reliable methods for early detection of ATC as well as for guiding transfusion requirements. Summary Hemorrhage accounts for up to 40% of human trauma-related deaths and remains the leading cause of preventable death in human trauma. The exact proportion of trauma-related deaths due to exsanguinations in veterinary patients remains uncertain. Survivability depends upon achieving rapid definitive hemostasis, early attenuation of posttraumatic coagulopathy, and timely restoration of effective circulating volume. Early institution of damage control resuscitation in severely injured patients with uncontrolled hemorrhage has the ability to curtail posttraumatic coagulopathy and the exacerbation of metabolic acidosis and hypothermia and improve survival until definitive hemostasis is achieved.OBJECTIVE To discuss the current resuscitative strategies for trauma-induced hemorrhagic shock and acute traumatic coagulopathy (ATC). ETIOLOGY Hemorrhagic shock can be acutely fatal if not immediately and appropriately treated. The primary tenets of hemorrhagic shock resuscitation are to arrest hemorrhage and restore the effective circulating volume. Large volumes of isotonic crystalloids have been the resuscitative strategy of choice; however, data from experimental animal models and retrospective human analyses now recognize that large-volume fluid resuscitation in uncontrolled hemorrhage may be deleterious. The optimal resuscitative strategy has yet to be defined. In human trauma, implementing damage control resuscitation with damage control surgery for controlling ongoing hemorrhage, acidosis, and hypothermia; managing ATC; and restoring effective circulating volume is emerging as a more optimal resuscitative strategy. With hyperfibrinolysis playing an integral role in the manifestation of ATC, the use of antifibrinolytics (eg, tranexamic acid and aminocaproic acid) may also serve a beneficial role in the early posttraumatic period. Considering the sparse information regarding these resuscitative techniques in veterinary medicine, veterinarians are left with extrapolating information from human trials and experimental animal models. DIAGNOSIS Viscoelastic tests integrated with predictive scoring systems may prove to be the most reliable methods for early detection of ATC as well as for guiding transfusion requirements. SUMMARY Hemorrhage accounts for up to 40% of human trauma-related deaths and remains the leading cause of preventable death in human trauma. The exact proportion of trauma-related deaths due to exsanguinations in veterinary patients remains uncertain. Survivability depends upon achieving rapid definitive hemostasis, early attenuation of posttraumatic coagulopathy, and timely restoration of effective circulating volume. Early institution of damage control resuscitation in severely injured patients with uncontrolled hemorrhage has the ability to curtail posttraumatic coagulopathy and the exacerbation of metabolic acidosis and hypothermia and improve survival until definitive hemostasis is achieved.

Platelet transfusions: treatment options for hemorrhage secondary to thrombocytopenia.

Objective To review current human and veterinary protocols for platelet transfusion triggers, available platelet transfusion products to support veterinary thrombocytopenic patients, and the advantages and disadvantages of each product. Data Sources Data from human and veterinary literature. Human Data Synthesis Prophylactic and therapeutic platelet transfusions are instrumental in managing human patients with thrombocytopenia. The platelet transfusion products used in human medicine consist of platelet concentrates, derived from pooled random donor platelets, or single-donor apheresis platelets. Historically, platelet transfusions in human medicine have been prophylactic in nature; however, recent research suggests changing from a prophylactic transfusion strategy to a therapeutic transfusion strategy may be safe for most patients. The optimal platelet transfusion trigger and the use of prophylactic verses therapeutic platelet transfusions are ever changing in human medicine. Veterinary Data Synthesis There have been many advances in platelet transfusion products, but fresh whole blood remains the most commonly used platelet transfusion product in veterinary medicine. New products such as lyophilized platelets and cryopreserved platelets offer the benefits of long shelf life, immediate availability, and higher concentration of platelets at smaller doses. Veterinary platelet transfusion guidelines are mostly extrapolated from human literature because data on veterinary platelet transfusions are lacking. Conclusions In veterinary medicine the most commonly available product for platelet transfusions is fresh whole blood, because of availability of blood donors and lack of a cost effective easily obtainable alternative. Cryopreserved and lyophilized platelets are promising new products being used in the treatment of hemorrhaging patients with thrombocytopenia. These products offer increased platelet concentrations at decreased volumes, longer storage shelf life, and decreased exposure to whole blood products. With the development of newer readily available products, platelet transfusion parameters, to include dose, platelet count trigger, presence of disease, and clinical signs, should be further evaluated in veterinary medicine.OBJECTIVE To review current human and veterinary protocols for platelet transfusion triggers, available platelet transfusion products to support veterinary thrombocytopenic patients, and the advantages and disadvantages of each product. DATA SOURCES Data from human and veterinary literature. HUMAN DATA SYNTHESIS Prophylactic and therapeutic platelet transfusions are instrumental in managing human patients with thrombocytopenia. The platelet transfusion products used in human medicine consist of platelet concentrates, derived from pooled random donor platelets, or single-donor apheresis platelets. Historically, platelet transfusions in human medicine have been prophylactic in nature; however, recent research suggests changing from a prophylactic transfusion strategy to a therapeutic transfusion strategy may be safe for most patients. The optimal platelet transfusion trigger and the use of prophylactic verses therapeutic platelet transfusions are ever changing in human medicine. VETERINARY DATA SYNTHESIS There have been many advances in platelet transfusion products, but fresh whole blood remains the most commonly used platelet transfusion product in veterinary medicine. New products such as lyophilized platelets and cryopreserved platelets offer the benefits of long shelf life, immediate availability, and higher concentration of platelets at smaller doses. Veterinary platelet transfusion guidelines are mostly extrapolated from human literature because data on veterinary platelet transfusions are lacking. CONCLUSIONS In veterinary medicine the most commonly available product for platelet transfusions is fresh whole blood, because of availability of blood donors and lack of a cost effective easily obtainable alternative. Cryopreserved and lyophilized platelets are promising new products being used in the treatment of hemorrhaging patients with thrombocytopenia. These products offer increased platelet concentrations at decreased volumes, longer storage shelf life, and decreased exposure to whole blood products. With the development of newer readily available products, platelet transfusion parameters, to include dose, platelet count trigger, presence of disease, and clinical signs, should be further evaluated in veterinary medicine.