Haemodynamic effects of small volume hypertonic saline in experimentally induced haemorrhagic shock

A comparison of the haemodynamic benefits of small volume hypertonic saline (2,400 mOsm/litre) versus isotonic saline (300 mOsm/litre) was conducted in 12 adult horses using a haemorrhagic shock model. The horses were anaesthetised and intravascular catheters placed for the measurement of haemodynamic data. Mean systemic arterial pressure was then reduced to 50 to 60 mmHg by controlled haemorrhage and maintained at that level for 40 mins. Cardiac output, stroke volume, mean systemic arterial pressure, plasma volume and urine production decreased significantly following blood loss. Hypertonic or isotonic saline was administered randomly by intravenous infusion and haemodynamic data recorded for a 2 h period. Treatment with hypertonic saline produced rapid elevations in cardiac output, stroke volume, mean systemic and pulmonary arterial pressures, cardiac contractility and urine output, and was accompanied by expansion of the plasma volume. The changes in cardiac output and stroke volume were maintained for the duration of the recording period, whereas increases in mean systemic arterial pressure were not as remarkable. Infusion of isotonic saline caused only transient increases in cardiac output and mean systemic and pulmonary arterial pressure, and cardiac output; urine output and plasma volume did not change. This study indicates that hypertonic saline produces haemodynamic improvements in experimentally induced haemorrhagic shock in horses.     

Fluid therapy for the traumatized patient

Objective: To review the rationale behind and experiences with traditional and newly evolving concepts of fluid therapy in the traumatized patient, and to review conventional and novel fluid preparations for use in trauma resuscitation. Data sources: Human and veterinary clinical and research studies. Human data synthesis: Current treatment guidelines recommend aggressive fluid resuscitation with lactated ringers solution (LRS) or saline as optimum management of hemorrhagic shock in trauma, regardless of whether bleeding is controlled or not. The rationale behind this strategy is to restore intravascular volume as rapidly as possible to ensure adequate vital organ perfusion. Recently, this strategy has been challenged, especially in patients with uncontrolled hemorrhage, as neither laboratory evidence nor clinical trials support this practice. Current research indicates that vigorous fluid infusion may exacerbate bleeding and cause severe hemodilution, both impairing resuscitation outcome. As a result, a new line of thinking is emerging that balances the risks and benefits of intravenous volume infusion by offering the clinician alternative treatment strategies and emphasizes continuous endpoint‐oriented monitoring. ‘Hypotensive’ or ‘hypovolemic’ resuscitation techniques as well as initial volume replacement with fluids other than LRS or saline (e.g., hypertonic saline [HTS], HTS with dextran 70 [HTS‐D]) have been introduced in human medical practice as additional options for treatment of victims of trauma under certain circumstances. Clinical studies evaluating the use of hemoglobin‐based oxygen carriers (HBOCs) in the trauma setting are underway and may soon lead to an expansion of the fluid arsenal available to the clinician for treatment of trauma patients. Veterinary data synthesis: Based on available animal data, neither strict guidelines nor a clear fluid preference for resuscitation of traumatic shock have been defined. Although systematic clinical trials are missing, combinations of crystalloid and colloid (natural or artificial) appear to be as effective for resuscitation as crystalloid alone. Judicious use of an HBOC (e.g., Oxyglobin^®) as a substitute for blood/red blood cells may be recommended in situations where whole blood or pRBCs are not or not yet available. Conclusions: The search for optimal methods of fluid resuscitation in trauma is ongoing. At this point the best solution is a differentiated approach to fluid therapy, one that tailors type and volume of resuscitation solution(s) used to the type and severity of injury in an individual patient and uses monitoring of perfusion and oxygenation parameters to guide resuscitation. Crystalloid fluids are effective for resuscitation but may need to be combined with or replaced by colloidal fluids in certain clinical situations.     

Complications of fluid therapy.

The intravenous administration of fluids is one of the most important aspects of patient care in hospitalized animals. Intravenous fluids are administered to replace or prevent dehydration, treat hypovolemic shock and intravascular volume depletion, correct acid-base and electrolyte abnormalities, and maintain vascular access for administration of drugs, blood product components, and parenteral nutrition. Intravenous catheterization also can provide a means of blood sample collection, thus avoiding frequent and uncomfortable venipunctures in critically ill animals. Although the benefits of intravenous catheterization and fluid administration are numerous, inherent risks are associated with the procedures, and care must be taken to avoid potential complications.     

What is shock?

Shock is a caricature of the physiological response to haemorrhage; as it progresses, the defensive attributes are replaced by adverse effects on circulation, reticuloendothelial function, respiration and metabolism. Haemorrhage is only one possible cause of shock and any severe reduction of circulating fluid volume can potentially trigger similar responses. Indeed despite the existence of several types of shock (e.g. anaphylactic, endotoxin, septic) the ‘final common path’ is remarkably similar and consists of a widespread failure of capillary perfusion. The essential prerequisite for effective perfusion is not merely the presence of blood in capillaries but its efficient movement through them. Thus viscosity is a key property of blood in shock and a limited fall in PCV may improve oxygen delivery. The pathophysiology of shock is discussed in relation to its therapeutic implications, notably the relative importance of fluid therapy, antibiotics and corticosteroids, the limitations on the effectiveness of antihistamines and α-blockers, and more recent work with Mg-ATP, hypertonic solutions, prostaglandins, endogenous opiates and dopamine.     

Roles of thromboxane A2 and 5-hydroxytryptamine in endotoxin-induced digital vasoconstriction in horses

OBJECTIVE: To evaluate the roles of 5-hydroxytryptamine (5-HT), thromboxane A2 (TxA2), and platelet-activating factor (PAF) in endotoxin-induced digital hypoperfusion in horses. ANIMALS: 6 healthy adult Thoroughbreds. PROCEDURES: Horses were treated with IV administration of saline (0.9% NaCl) solution (control treatment) or the 5-HT 1B/D selective antagonist, GR55562 (0.3 mg/kg), prior to tryptamine infusion (1.6 microg/kg/min for 30 minutes) to establish an effective GR55562 dose. In a crossover study, horses were treated with IV administration of saline solution (control treatment), aspirin (4 mg/kg, 2 hours or 4 days before lipopolysaccharide [LPS] infusion), GR55562 (0.3 mg/kg), the PAF antagonist WEB2086 (3 mg/kg), or aspirin plus GR55562 prior to LPS infusion (30 ng/kg for 30 minutes). Digital blood flow was measured by use of Doppler ultrasonography. Concomitant measurements of hoof wall and coronary band surface temperatures were made. Serial blood samples were collected and plasma 5-HT and TxA2 concentrations determined. RESULTS: GR55562 abolished tryptamine-induced digital hypoperfusion. Neither WEB2086 nor GR55562 affected LPS-induced alterations in digital perfusion or plasma mediator concentrations. Aspirin given 2 hours before LPS administration abolished the increase in plasma TxA2 concentration and significantly attenuated LPS-induced digital hypoperfusion. Aspirin given 4 days before LPS significantly attenuated the increase in plasma TxA2 concentration and digital hypothermia. Aspirin plus GR55562 had a greater effect on LPS-induced digital hypothermia than aspirin alone. CONCLUSIONS AND CLINICAL RELEVANCE: Thromboxane A2 and 5-HT played a role in mediating LPS-induced digital hypoperfusion in horses. Platelet-activating factor appeared unimportant in mediating LPS-induced 5-HT or TxA2 release or digital hypoperfusion.     

Treatment of reperfusion injury in dogs with experimentally induced gastric dilatation-volvulus.

In dogs, gastric dilatation-volvulus (GDV) is characterized by cardiogenic shock, with resulting hypoperfusion. Treatment goals include reperfusion of transiently ischemic tissues, which indicates that reperfusion injury may be a factor in the physiopathogenesis of GDV. Recently, we obtained data that indicate that reperfusion injury may be involved in experimentally induced GDV. Using this GDV model, we evaluated mortality in 24 dogs of 4 equal groups, treated with deferoxamine (an iron chelator), dimethylsulfoxide (a free radical scavenger), a combination of the 2 drugs, or isotonic saline solution. All 6 dogs that were given deferoxamine survived; however, 3 dogs of the dimethylsulfoxide-treated group, 2 dogs of the combination-treated group, and 4 dogs of the saline-treated group died. Results of the study indicate that mortality associated with experimentally induced GDV is reduced by appropriate and timely pharmacologic intervention to prevent or attenuate reperfusion injury, and that deferoxamine may be more effective than dimethylsulfoxide.     

Vasopressin therapy in dogs with dopamine-resistant hypotension and vasodilatory shock

Objective: To describe the therapeutic use of vasopressin in dogs with dopamine‐resistant hypotension and vasodilatory shock. Series summary: We report the effects of intravenous vasopressin therapy on mean arterial blood pressure and central venous pressure (CVP) in 5 dogs with dopamine‐resistant hypotension from vasodilatory shock. All subjects had documented hypotension and vasodilation, despite adequate intravascular volume and catecholamine therapy. There was an increase in mean arterial pressure following vasopressin administration. No cardiac arrhythmias were noted, nor were there clinically significant changes in CVP. New information provided: Mean arterial blood pressure increased following vasopressin therapy in all of the dogs. Vasopressin may prove useful in the treatment of vasodilatory shock, however further research is warranted.     

Optimal endpoints of resuscitation and early goal-directed therapy

Objective: To review the available endpoints of shock resuscitation, including traditional perfusion parameters, oxygen‐transport variables, lactate, base deficit (BD), venous oxygen saturation, and gastric mucosal pH, and to discuss the currently accepted methods of assessing successful reversal of oxygen (O₂) debt in shock patients. Human‐based studies: Early goal‐directed therapy has unequivocally been shown to positively affect outcome in human patients experiencing cardiovascular shock. However, specific endpoints of resuscitation to target in critically ill patients remain controversial. Reliance on traditional endpoints of resuscitation (heart rate [HR], blood pressure [BP]) appears insufficient in detection of ongoing tissue hypoxia in shock states. A multitude of publications exist suggesting that indirect indices of global (lactate, base deficit, mixed/central venous oxygen saturation), regional (gastric intramucosal pH [pH_i]) and cellular (transcutaneous oxygen) oxygenation are more successful in outcome prediction and in assessing adequacy of resuscitative efforts in this patient population. Veterinary‐based studies: While there are several large studies evaluating endpoints of resuscitation in experimental canine shock models, this author was unable to find similar research pertaining to small animal veterinary patients. The few articles in which blood lactate is evaluated for prognostic purposes in canine patients are included in this review. Data sources: Veterinary and human literature review. Conclusions: Optimization of early resuscitative efforts has proven to have a survival benefit in human shock patients, and major strides have been made in determining which endpoints of resuscitation to target in this patient population. Similar clinical trials designed to evaluate indices of ongoing global and regional tissue hypoxia in small animal veterinary shock patients are warranted.     

Effects of flunixin meglumine on blood pressure and fluid compartment volume changes in ponies given endotoxin

A study was conducted to determine whether body fluids undergo a net shift from one compartment to another during endotoxin-induced shock in the pony, and whether flunixin meglumine alters these endotoxin-induced changes in the volumes of body fluid compartments. Total blood, RBC, and plasma volumes were determined, using 51Cr-labeled RBC and PCV that were corrected for trapped plasma. Total body water was measured by distribution of 3HOH. Arterial blood pressure was measured directly, using a blood pressure transducer. Treatment (flunixin meglumine, 1.1 mg/kg of body weight) was given to 6 of the 12 ponies 1 minute before an IV injection of Escherichia coli endotoxin (100 micrograms/kg of body weight, LD100). The PCV and RBC volume increased in both groups; however, the hemoconcentration was less in flunixin meglumine-treated ponies. In nontreated ponies, total blood volume and plasma volume decreased significantly during the first hour after endotoxin administration. In treated ponies, total blood volume did not vary significantly, and plasma volume decreased only slightly. In both groups, the increase in PCV was apparently due to splenic contraction, which increased the number of circulating RBC. Hemoconcentration was further increased in nontreated ponies by the loss of plasma into the interstitial space. Flunixin meglumine reduced plasma loss, minimized hemoconcentration, and maintained normal blood volume. Total body water remained constant in treated and nontreated ponies.     

The Evaluation of Coagulation Profiles in Calves with Suspected Septic Shock

The purpose of the study reported here was to evaluate the haemostatic function in calves with suspected septic shock and to reflect the occurrence of disseminated intravascular coagulation (DIC). Twenty-six calves suspected of having septic shock (experimental group) and 10 clinically healthy calves (control group) were used. On admission, the experimental group of calves had been ill for an average of 2 days. Therapy was applied to the experimental group of calves. The packed cell volume (PCV), haemoglobin (Hb), white blood cell (WBC), red blood cell (RBC) and platelet (PLT) counts were determined. Blood smears for toxic neutrophil and schistocyte intensity were evaluated. For the coagulation profile, plasma activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen and fibrin/fibrinogen degradation products (FDPs) values were determined. Toxic neutrophils in blood smears were observed in 12 calves of the experimental group. APTT was prolonged in the experimental group compared with the control group (p < 0.05). Fibrinogen concentration was found to be higher in the experimental group than in the control group (p < 0.001). Total leukocyte counts were higher in the experimental group compared with the control group (p < 0.01). Platelet counts in the experimental group were lower than the control group (p < 0.001). However, when the individual values of coagulation profiles of each calf were evaluated, 8 calves had at least three abnormal coagulation profiles (APTT >72 s, PT >34.5 s, TT >33.7 s, FDPs >5 microg/ml, PLT < or = 150 x 10(3)/mm(3)) and abnormal erythrocyte morphology (schistocytes > or = 1). The most common abnormal tests in the coagulation profile were APTT and PT (7 cases), FDPs (6 cases), thrombocytopenia (4 cases), and schistocytes in blood smears (8 cases) in these 8 calves. The results of this study indicate that DIC might be a significant risk factor for mortality in calves with suspected septic shock.     

Cardiogenic shock and cardiac arrest.

Severe heart disease may cause hypotension and hypoperfusion, and ultimately circulation may cease altogether. These two clinical syndromes are cardiogenic shock and cardiac arrest, respectively. This review summarizes the causes and clinical features of each, and describes the treatment options available to clinicians managing patients in cardiogenic shock.     

Mammary gland carcinoma in a dog with peripheral blood and bone marrow involvement associated with disseminated intravascular coagulation

A 7-year-old female Leonberger dog was referred to the National Veterinary School of Lyon Teaching Hospital with a 2-day history of anorexia and bleeding. A mammary mass had been removed 7 months earlier, but histologic examination was not performed. On physical examination, the dog was depressed and had pale mucous membranes and numerous petechiae and hematomas. Significant laboratory findings were moderate thrombocytopenia, prolonged prothrombin, activated partial thromboplastin, and thrombin times, hypofibrinogenemia, and increased concentration of fibrin(ogen) degradation products. A peripheral blood smear, buffy coat preparation, and bone marrow aspirate contained low numbers of large atypical cells that had moderate nuclear:cytoplasmic ratios, oval nuclei with multiple prominent nuclei, and basophilic cytoplasm with villous projections. A small nodule was found in the left inguinal mammary gland, and a fine-needle aspirate contained cells similar to those in blood and bone marrow. In samples of blood, bone marrow, and the mammary mass, the neoplastic cells were immunoreactive for cytokeratin. The diagnosis was mammary carcinoma with secondary disseminated intravascular coagulation (DIC) and disseminated tumor cells in bone marrow and circulating tumor cells in blood; this diagnosis was not confirmed by histopathologic examination. Owing to clinical deterioration and the poor prognosis, the dog was euthanized and a necropsy was not performed. This is the first report of a canine mammary carcinoma with circulating tumor cells and secondary DIC.     

Pharmacologic management of circulatory shock: cardiovascular drugs and corticosteroids.

Effective use of cardiovascular drugs in the management of circulatory shock requires knowledge of the pathophysiologic changes occurring in the different types and stages of shock and an understanding of the specific hemodynamic actions of drugs used to correct shock. Objectives of therapy are to: (1) restore circulating blood volume, (2) ensure of increase perfusion of critical organs by selectively reducing arteriolar resistance, (3) augment cardiac output, and (4) increase perfusion pressure. If blood volume is not restored, drugs may be ineffective and can even induce deleterious effects. If reflex sympathetic discharge has induced generalized vasoconstriction, it is irrational to expect beneficial results from administration of exogenous vasconstrictor agents. Instead, selective vasodilatation of vascular beds in critical tissues (eg, myocardium, intestines, and kidneys) accompanied by increased perfusion pressure and cardiac output can prove useful. Large doses of adrenocorticosteroids are used commonly in the therapy of different shock conditions, based primary on empiric tests of efficacy. Although such steroids may not influence the course of shock by direct cardiovascular effects, beneficial actions may result from mechanisms such as protection of cell membrane integrity and stabilization of lysosomes.     

Intravascular macrophages in lungs of pigs infected with Haemophilus pleuropneumoniae

Pigs were inoculated intratracheally with a virulent or an avirulent isolate of Haemophilus pleuropneumoniae serotype 5 and sacrificed during the first 24 hours post-inoculation. Intravascular macrophages were examined by electron microscopic and morphometric techniques. Samples of lung were taken from regions with no macroscopic lesions (Zone 0), 2.5 to 3.0 cm from lesions (Zone 1), and from the immediate edge of lesions (Zone 2). Those pigs inoculated with the avirulent isolate did not develop lesions. Pigs given the virulent isolate consistently developed necrohemorrhagic lesions in the dorsolateral aspect of the caudal and middle lung lobes. Relative volumes of intravascular macrophages in Zones 1 and 2 increased with increased time post-inoculation; in pigs given the avirulent isolate, intravascular macrophage volume decreased with increased time post-inoculation. Cytoplasmic volume to nuclear volume ratios for macrophages in Zone 2 from pigs with necrohemorrhagic lesions progressively increased with increased time post-inoculation. Enlarged intravascular macrophages had large nuclei, prominent nucleoli, and abundant cytoplasm. Increased cytoplasmic volume was the result of increased numbers of lysosomes, phagosomes, rough and smooth endoplasmic reticulum, and large Golgi complexes. Pigs inoculated with the virulent bacteria had IV macrophages with large phagosomes that contained necrotic cell debris and fibrin. Macrophages with phagosomes were more frequent in the 6-, 9-, and 24-hour sample periods of pigs with lesions than in any other group. Intercellular adhesion plaques (ICAP) were present between IV macrophages and subjacent endothelial cells. ICAP's increased in length with increased time post-inoculation in Zones 1 and 2 from pigs with necrohemorrhagic lesions. In later sample periods, multiple closely associated and interlacing IV macrophages formed a discontinuous layer over endothelial cells in Zone 2 samples near necrohemorrhagic lesions. These results suggest that the intravascular macrophage population changes from immature macrophages to mature macrophages or immature epithelioid cells within 24 hours after inhalation of a virulent Haemophilus pleuropneumoniae. Furthermore, intravascular macrophages likely function to clear cellular and acellular debris from the blood in pneumonic conditions.     

Multiple endocrine abnormalities in Basenji dogs with renal tubular dysfunction

Three Basenji dogs with renal tubular dysfunction were studied. Hyposthenuria and diminished urine concentrating ability, indicative of nephrogenic diabetes insipidus, were documented. Metabolic acidosis, hyperchloremia, and reduction in glomerular filtration rate also were detected in all dogs. In addition, an exaggerated response to the adrenocorticotropin test and hyperaldosteronism, believed to be secondary to decreased effective circulating blood volume, were detected in all 3 dogs. Thyroxine values were decreased in all dogs and could be correlated with histopathologic changes of the thyroid gland in 2 dogs. Gastropathy and hypergastrinemia were identified in 2 dogs. Diffuse lymphocytic-plasmacytic enteritis was evident in 2 dogs. It was concluded that a urine concentrating defect that may be secondary to hypercortisolism exists in Basenji dogs with renal tubular dysfunction.     

Packed cell volume (PCV) in connection with uterine prolapse and in parturient paresis in cows.

Packed cell volume was determined in 317 cows with uterine prolapse, the condition being in more than half of these cases associated with varying degrees of hypocalcaemia, in 133 cows with parturient paresis and in 73 clinically healthy newly calved cows. Independently of each other uterine prolapse and fall in plasma calcium were associated with a significant rise in PCV. The present investigation demonstrated a marked fall in circulating blood volume in a considerable number of cows suffering from uterine prolapse. The risk of irreversible hypovolemic shock developing in connection with uterine prolapse is not to be neglected, and may be aggravated by the simultaneous occurrence of hypocalcaemia, as several of the compensatory mechanisms are calcium dependent.     

Treatment of Dogs in Hemorrhagic Shock by Intraosseous Infusion of Hypertonic Saline and Dextran

Under isoflurane anesthesia, 50% of the calculated blood volume was removed from 11 dogs. After 30 minutes, five dogs were treated with hypertonic saline and dextran (HSD) (5 mL/kg) followed by isotonic saline solution (2 mL/kg) intraosseously. Six dogs (controls) received isotonic saline (7 mL/kg) intraosseously. All treatments were administered through the medullary cavity of the tibia over a 30-minute period. Cardiac output, mean arterial pressure, central venous pressure, packed cell volume, total protein, and blood gases were monitored for 4 hours. Cardiac output, mean arterial pressure, and circulating volume (indicated by packed cell volume and total protein) were significantly improved after administration of HSD. We conclude that intraosseous infusion of HSD is efficacious in treating hemorrhagic shock and believe the technique may prove to be useful in clinical situations when intravenous lines cannot be established rapidly.     

Toxicity studies with the blue-green alga Oscillatoria agardhii from two eutrophic Norwegian lakes

Extracts of the blue-green alga Oscillatoria agardhii were tested for acute toxicity on laboratory mice and rats. Material originating from lake Gjersjøen proved to be toxic to the animals, samples from the nearby lake Årungen did not. Clinical symptoms culminated in the development of a fatal shock due to decrease in circulating blood volume. Pathological examination revealed heavy pooling of blood in the liver and severe damage to the organ. Blood analyses also indicated liver damage. Effects were the same with extracts from a laboratory clone culture as from a natural water bloom, but the toxin content was higher in the bloom material. Toxicity was not affected by heat, acid or alkali treatment.     

Percutaneous endovascular retrieval of an intravascular foreign body in five dogs, a goat, and a horse

CASE DESCRIPTION-5 Dogs, 1 goat, and 1 horse underwent percutaneous endovascular retrieval of intravascular foreign bodies between 2002 and 2007. CLINICAL FINDINGS-Foreign bodies were IV catheters in 4 dogs, the horse, and the goat and a piece of a balloon valvuloplasty catheter in 1 dog. Location of the foreign bodies included the main pulmonary artery (1 dog), a branch of a pulmonary artery (4 dogs), the right ventricle (the goat), and a jugular vein (the horse). TREATMENT AND OUTCOME-The procedure of percutaneous endovascular retrieval of the foreign body was easy to perform in all instances. One dog was euthanized 41 days after retrieval because of worsening of another disease process, and 1 dog had abnormal neurologic signs secondary to a brain mass. All other animals were clinically normal during the follow-up period (follow-up duration, 3 to 57 months). None of the animals developed long-term complications secondary to the foreign body retrieval procedure. CLINICAL RELEVANCE-Intravascular foreign bodies that result from catheters or devices used during minimally invasive techniques are rare but may cause substantial morbidity. Percutaneous endovascular retrieval of intravascular foreign bodies was easily and safely performed in the 7 animals reported here. Use of percutaneous endovascular retrieval techniques should be considered for treatment of animals with intravascular foreign bodies because morbidity can be substantially decreased; however, proper selection of patients for the procedure is necessary.     

Evaluation of the ability to regulate blood volume under standardized motoric stress]

Sixteen German Landrace pigs of the meat type were kept in individual cages (0.47 m2 floor area each) or in two pens of four pigs providing 1.05 m2 per animal, under otherwise identical conditions for 45 days, commending at a body weight of 45 kg. Plasma volume and plasma glucose were determined before, during and after the pigs made to run on a band moving at 1 m/s for 20 minutes at 24 degrees C. Changes in plasma volume were studied from the total scatter of values (total area covered by the curve of values). This made it possible to quantify individual regulatory capacity and the influence of management. Close confinement in an individual cage reduced the regulatory capacity of the plasma volume by 3.5 to 4 times. There were significant qualitative and quantitative relationships between intravascular fluid volume and intravascular glucose or glucose concentration.