Rebecca Kirby

Systemic Inflammatory Response Syndrome: Septic Shock

The systemic inflammatory response syndrome (SIRS) is the bodys response to a multitude of chemical mediators. Conditions inciting the release of these mediators include bacterial sepsis, viremia, pancreatitis, trauma, neoplasia, heat stroke, and many others. The key to the successful management of SIRS lies in anticipation and not reaction. Resuscitation of the patient to supranormal levels, coupled with aggressive monitoring and support of target organs are essential.

Evaluation of initial plasma lactate values as a predictor of gastric necrosis and initial and subsequent plasma lactate values as a predictor of survival in dogs with gastric dilatation-volvulus: 84 dogs (2003–2007)

OBJECTIVE To test whether an initial plasma lactate ≥ 6.0 mmol/L is associated with the presence of macroscopic gastric wall necrosis and overall survival in dogs presenting with gastric dilatation-volvulus (GDV). Additionally, if no association was identified we sought to identify a different predictive initial plasma lactate concentration and to examine whether serial plasma lactate concentrations provide better prediction of survival. DESIGN Retrospective study over a 5-year period (2003-2007). SETTING Urban private referral small animal teaching hospital. ANIMALS Eighty-four client-owned dogs with a diagnosis of GDV and plasma lactate measurements. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS There was no statistically significant relationship found between survival and the presence of macroscopic gastric wall necrosis with the initial plasma lactate ≥ 6 mmol/L. There was a significant relationship between the initial plasma lactate >2.9 mmol/L for predicting necrosis and <4.1 mmol/L for predicting survival to discharge. Forty dogs that had an increased initial plasma lactate (>2.5 mmol/L) also had a subsequent plasma lactate measured within 12 hours of presentation, with 37/40 dogs surviving and 70% of these surviving dogs having the subsequent lactate decrease by ≥ 50% within 12 hours. The 3/40 that died failed to decrease their plasma lactate by ≥ 50% from the initial blood lactate. CONCLUSION The results of this study indicate that an initial presenting plasma lactate concentration ≥ 6.0 mmol/L is not predictive of macroscopic gastric wall necrosis or survival in dogs presenting with GDV. A decrease in plasma lactate concentrations ≥ 50% within 12 hours may be a good indicator for survival. Limitations to the study include its retrospective nature, the small number of patients, and the number of dogs that were euthanized rather than allowed to progress to a natural outcome.

Apoptosis: A review of pro-apoptotic and anti-apoptotic pathways and dysregulation in disease

Abstract Objective – To review the human and veterinary literature on the biology of apoptosis in health and disease. Data Sources – Data were examined from the human and veterinary literature identified through Pubmed and references listed in appropriate articles pertaining to apoptosis. Human Data Synthesis – The role of apoptosis in health and disease is a rapidly growing area of research in human medicine. Apoptosis has been identified as a component of human autoimmune diseases, Alzheimers disease, cancer, and sepsis. Veterinary Data Synthesis – Research data available from the veterinary literature pertaining to apoptosis and its role in diseases of small animal species is still in its infancy. The majority of veterinary studies focus on oncologic therapy. Most of the basic science and human clinical research studies use human blood and tissue samples and murine models. The results from these studies may be applicable to small animal species. Conclusions – Apoptosis is the complex physiologic process of programmed cell death. The pathophysiology of apoptosis and disease is only now being closely evaluated in human medicine. Knowledge of the physiologic mechanisms by which tissues regulate their size and composition is leading researchers to investigate the role of apoptosis in human diseases such as cancer, autoimmune disease and sepsis. Because it is a multifaceted process, apoptosis is difficult to target or manipulate therapeutically. Future studies may reveal methods to regulate or manipulate apoptosis and improve patient outcome.

Hydroxyethyl starch: A review of pharmacokinetics, pharmacodynamics, current products, and potential clinical risks, benefits, and use

Objective To review and summarize the pharmacokinetics and pharmacodynamics of hydroxyethyl starch (HES), as well as reported risks and benefits of HES infusion, and to provide administration and monitoring recommendations for HES use in dogs and cats. Data Sources Veterinary and human peer-reviewed medical literature, including scientific reviews, clinical and laboratory research articles, and authors’ clinical experience. Summary HES solutions are the most frequently used synthetic colloid plasma volume expanders in human and veterinary medicine. The majority of research in human medicine has focused on the adverse effects of HES infusion, with emphasis on acute kidney injury and coagulation derangements. The studies often differ in or fail to report factors, such as the type, amount, interval, and concentration of HES administered; the patient population studied; or concurrent fluids administered. Currently, there is no definitive clinical evidence that the reported adverse effects of HES use in human medicine occur in veterinary species. There is little information available on HES administration techniques or simultaneous administration of additional fluids in human and veterinary medicine. The rationale for HES use in small animals has been largely extrapolated from human medical studies and guidelines. A controlled approach to intravenous fluid resuscitation using crystalloid and HES volumes titrated to reach desired resuscitation end point parameters is outlined for small animal practitioners. Conclusion The extrapolation of data from human studies directly to small animals should be done with the knowledge that there may be species variations and different pharmacokinetics with different HES solutions. Veterinary reports indicate that bolus and continuous rate infusions of 6% hetastarch solutions at moderate doses are well tolerated in feline and canine subjects. Further research in domesticated species is necessary to better define and expand the knowledge regarding use of HES solutions in small animal medicine.

The role of aquaporin 4 in the brain

Emerging evidence suggests that aquaporin (AQP) 4 water channels play an important role in water homeostasis in the brain. These water channels are most abundant in the cell membrane of astrocytes, but are also present within ependymal cell membranes and in osmosensory areas of the hypothalamus. Water transport through AQP4 depends on concentration gradients across the membrane, but the rate of transport is determined by the capacity of astrocytes to up- and down-regulate AQP4 numbers, their location within the membrane, and the overall permeability of the channel. Other functions of brain AQP4 involve potassium uptake and release by astrocytes, migration of glial cells, glial scarring, and astrocyte-to-astrocyte cell communication. AQP water channels are involved in formation and control of edema in the brain and in multiple disease processes in the brain, such as seizures and tumors. There is abundant scientific literature on AQP4 describing its structure, function, location, and role in water homeostasis and edema in the brain. Investigation of AQP expression in the canine and feline brain should be pursued so that clinically relevant comparisons between findings in mice, rats, and people and animal patients can be made.

Nasogastric tube feeding in cats with suspected acute pancreatitis: 55 cases (2001–2006)

OBJECTIVE To evaluate the complications and outcome associated with different nasogastric tube (NGT) feeding techniques in cats with suspected acute pancreatitis. DESIGN Descriptive retrospective case series. SETTING Small animal emergency and referral hospital. ANIMALS The patient database (2001-2006) was searched for cats with suspected acute pancreatitis that received NGT liquid enteral feeding within 72 hours of admission and ≥12 hours during hospitalization. MEASUREMENTS AND MAIN RESULTS Signalment, history, clinical signs, laboratory data and abdominal ultrasonographic examinations were used for suspected diagnosis. Cats were grouped based upon whether they received bolus feeding or continuous rate infusion (CRI) of a liquid diet via the NGT, and whether or not administration of an intravenous amino acid and carbohydrate solution occurred prior to NGT feeding (AAS and non-AAS group, respectively). Fifty-five cats were included. For all cats, NGT feeding was initiated at a mean of 33.5 ± 15.0 hours and the target caloric intake (1.2 X {(30 X BW [kg]) +70}) was reached at 58.0 ± 28.4 hours from presentation. There was a significantly longer time from admission to the initiation of NGT feeding in the 34/55 cats in the AAS group vs. the 21/55 cats in the non-AAS group (P = 0.009). The 8 bolus-fed cats took longer to reach target caloric intake vs. the 47 CRI-fed cats (P = 0.002). Complications associated with NGT feeding for all cats included: mechanical problems (13%), diarrhea (25%), vomiting following NGT placement (20%) and vomiting following NGT feeding (13%). Mean time to discharge for all cats occurred after 78.6 ± 29.5 hours with an overall weight gain of 0.08 ± 0.52 kg. Fifty cats survived 28 days post-discharge. CONCLUSIONS NGT feeding in this group of cats with suspected acute pancreatitis was well tolerated, and associated with a low incidence of diarrhea, vomiting, and mechanical complications.

The role of glutamate, calcium and magnesium in secondary brain injury

Objective: To review the roles that glutamate, calcium and magnesium play in both normal brain function and in the events following traumatic brain injury. Human data synthesis: Elevated extracellular brain glutamate levels have been well documented in humans following traumatic brain injury. Therapies focusing on glutamate receptor antagonists have not yet been shown to have clinical effectiveness significant enough to outweigh the side effects. Newer strategies are currently being explored focusing on the many secondary cellular cascades interacting to culminate in cell injury and death. Veterinary data synthesis: Derangements in glutamate, calcium and magnesium have been well documented in animals following traumatic brain injury. Research studies using animal models other than small laboratory animals such as rats, mice and rabbits are very limited. Prospective veterinary clinical trials in dogs and cats are needed to determine the potential success that various therapeutic strategies might have in the field of small animal emergency and critical care medicine. Conclusions: Alterations in the levels of glutamate, calcium and magnesium play a critical role in secondary brain injury. The future development of clinically-tolerated and effective antagonists of glutamate, glutamate receptors, and other downstream mediators has the potential to revolutionize the therapy of traumatic brain injured patients.

Fluid Therapy: Crystalloids and Colloids

Appropriate fluid therapy requires an understanding of fluid dynamics and pathologic alterations during various disease states. In addition, it requires an understanding of the pharmacologic differences of available fluids. Crystalloid fluids and colloid fluids can be used in combination to treat a variety of volume-deficient states. Synthetic colloids are also used to treat hyponcotic states. Blood products are used to replace blood components and coagulation proteins. Frequent monitoring and reassessment are required to prevent volume overload and life-threatening edema.

Evaluation of the effects of bovine hemoglobin glutamer-200 on systolic arterial blood pressure in hypotensive cats: 44 cases (1997-2008)

OBJECTIVE To determine effects of bovine hemoglobin glutamer-200 (Hb-200) solution on systolic arterial blood pressure (SAP) in hypotensive cats and describe potential adverse effects associated with this treatment. DESIGN Retrospective case series. ANIMALS 44 cats. PROCEDURES Medical records of hypotensive (Doppler SAP ≤ 80 mm Hg) cats that received Hb-200 treatment were reviewed. Volume and rate of Hb-200 administration, treatments for hypotension given prior to Hb-200 administration, changes in SAP, potential adverse effects, and short-term outcome were evaluated. RESULTS 44 cats were included in the study. Mean ± SD SAP prior to Hb-200 administration was 52 ± 11 mm Hg, despite other treatments. Forty-three cats received Hb-200 via IV bolus administration (mean ± SD volume, 3.1 ± 2.2 mL/kg [1.41 ± 1.0 mL/lb] over 25.17 ± 17.51 minutes); 1 cat received a continuous rate infusion (CRI) only. The SAP increased to > 80 mm Hg in 33 of 44 (75%) cats. The SAP increased > 20 mm Hg above baseline value in 29 of these 33 cats and in 4 cats in which SAP did not exceed 80 mm Hg. A CRI (mean ± SD rate, 0.8 ± 0.5 mL/kg/h [0.36 ± 0.23 mL/lb/h]) of Hb-200 was administered to 37 cats (after bolus infusion in 36). Mean SAP during the CRI was 92 ± 18 mm Hg. Adverse effects included respiratory changes (n = 8 cats), vomiting (2), and pigmented serum (30). Seventeen (39%) cats survived to discharge from the hospital, 6 died, and 21 were euthanized. CONCLUSIONS AND CLINICAL RELEVANCE Hb-200 effectively increased SAP in hypotensive cats with few adverse effects.

Comparison of Hb‐200 and 6% hetastarch 450/0.7 during initial fluid resuscitation of 20 dogs with gastric dilatation‐volvulus

Objective To compare the use of polymerized stroma-free bovine hemoglobin (Hb-200) and 6% hetastarch 450/0.7 (HES 450/0.7) in 0.9% saline during fluid resuscitation of dogs with gastric dilatation-volvulus (GDV). Design Prospective, randomized clinical case series. Setting Private specialty and referral clinic. Animals Twenty client-owned dogs presenting with GDV. Interventions Dogs presenting with GDV and abnormal perfusion parameters first received rapid IV infusion of a buffered isotonic replacement crystalloid (15 mL/kg) and IV opioids. Patients were then randomized to receive either Hb-200 (N = 10) or HES 450/0.7 (N = 10). Balanced isotonic replacement crystalloids (10–20 mL/kg IV) were rapidly infused along with either Hb-200 or HES in 5 mL/kg IV aliquots to meet resuscitation end points. Measurements and Main Results Resuscitation was defined as meeting at least 2 of 3 criteria: (1) capillary refill time 1–2 seconds, pink mucous membrane color, strong femoral pulse quality; (2) heart rate (HR) ≤ 150/min; or (3) indirect arterial systolic blood pressure (SBP) > 90 mm Hg. HR, SBP, packed cell volume, hemoglobin, glucose, venous pH, bicarbonate, base excess, anion gap, and colloid osmotic pressure were compared at hospital entry and within 30 minutes post-resuscitation. Compared to the HES group, the Hb-200 group required significantly less colloid (4.2 versus 18.4 mL/kg) and crystalloid (31.3 versus 48.1 mL/kg) to reach resuscitation end points (P = 0.001). Time to resuscitation was significantly shorter in the Hb-200 group (12.5 versus 52.5 min). Conclusions Dogs with GDV receiving Hb-200 during initial resuscitation required smaller volumes of both crystalloid and colloid fluids and reached resuscitation end points faster than dogs receiving HES 450/0.7 (P = 0.02).OBJECTIVE To compare the use of polymerized stroma-free bovine hemoglobin (Hb-200) and 6% hetastarch 450/0.7 (HES 450/0.7) in 0.9% saline during fluid resuscitation of dogs with gastric dilatation-volvulus (GDV). DESIGN Prospective, randomized clinical case series. SETTING Private specialty and referral clinic. ANIMALS Twenty client-owned dogs presenting with GDV. INTERVENTIONS Dogs presenting with GDV and abnormal perfusion parameters first received rapid IV infusion of a buffered isotonic replacement crystalloid (15 mL/kg) and IV opioids. Patients were then randomized to receive either Hb-200 (N = 10) or HES 450/0.7 (N = 10). Balanced isotonic replacement crystalloids (10-20 mL/kg IV) were rapidly infused along with either Hb-200 or HES in 5 mL/kg IV aliquots to meet resuscitation end points. MEASUREMENTS AND MAIN RESULTS Resuscitation was defined as meeting at least 2 of 3 criteria: (1) capillary refill time 1-2 seconds, pink mucous membrane color, strong femoral pulse quality; (2) heart rate (HR) ≤ 150/min; or (3) indirect arterial systolic blood pressure (SBP) > 90 mm Hg. HR, SBP, packed cell volume, hemoglobin, glucose, venous pH, bicarbonate, base excess, anion gap, and colloid osmotic pressure were compared at hospital entry and within 30 minutes post-resuscitation. Compared to the HES group, the Hb-200 group required significantly less colloid (4.2 versus 18.4 mL/kg) and crystalloid (31.3 versus 48.1 mL/kg) to reach resuscitation end points (P = 0.001). Time to resuscitation was significantly shorter in the Hb-200 group (12.5 versus 52.5 min). CONCLUSIONS Dogs with GDV receiving Hb-200 during initial resuscitation required smaller volumes of both crystalloid and colloid fluids and reached resuscitation end points faster than dogs receiving HES 450/0.7 (P = 0.02).