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Endocrine and metabolic responses to plasma volume expansion during halothane anesthesia in ponies.
The study was designed to contribute to identification of the stimulus to adrenocortical activity during halothane anaesthesia in equidae. Two groups of six ponies were premedicated with acepromazine before induction of anaesthesia with thiopentone and maintenance for 120 min with halothane in oxygen. In group H Haemaccel modified gelatine plasma replacer was infused (48+/-13 mL/kg) to maintain mean arterial blood pressure (MABP) close to preanaesthetic values. In group DH, blood pressure was maintained close to preanaesthetic levels with a lower dose of Haemaccel (10 mL/kg) combined with an infusion of dobutamine. Measurements were made before anaesthesia, at 20 min intervals during anaesthesia and 20 and 120 min after anaesthesia. MABP and blood gases, pulse and respiratory rates were measured, and blood was withdrawn for assay of cortisol, adrenocorticotrophic hormone (ACTH), glucose and lactate. Ponies in both groups became hyperoxic, hypercapnic and developed a respiratory acidosis; pulse rate increased in both groups but this was more marked in group H. Haematocrit decreased by 50% in H and by 20% in DH. Cortisol and ACTH did not change significantly during anaesthesia in either group and the area under the time curve (AUC(0-140)) was lower in the DH group. Plasma glucose and lactate remained stable. After the H treatment all ponies had a watery nasal discharge and one pony died from endotoxaemia. This investigation demonstrated that the adrenocortical response to halothane anaesthesia in ponies can be ameliorated by manipulation of ABP using plasma expansion with or without inotrope infusion; however, low dose Haemaccel with dobutamine was safer and more practical. It is suggested that, although hypotension is not the sole stimulus to adrenocortical activity during halothane anaesthesia, it may contribute, probably through an effect on tissue perfusion.
Corpus cavernosum as an alternative means of intravenous access in the emergency setting.
BACKGROUND: The present study was designed to investigate the feasibility of using the corpus cavernosum as an alternative means of intravenous access in the emergency setting. METHODS: The feasibility of achieving the infusion flow rates was first ascertained using direct intracavernous infusion of normal saline. The effect of atropine and adrenaline when given via this route was then studied. Hypovolaemic shock was then induced in dogs who were then actively resuscitated via this route using normal saline, Haemaccel and whole blood. RESULTS: Infusion flow rates were achieved for normal saline of 32.3, 50.3 and 67.3 mL per min at 100, 200 and 300 mmHg pressure, respectively. The peak effects of atropine and adrenaline via this route were seen at approximately 1 min after injection. Resuscitation using this method was uniformly successful in all dogs via the corpus cavernosum, with all reaching or exceeding their premorbid central venous pressure (CVP), and approaching or reaching their premorbid mean arterial pressure (MAP). In comparison the control dog's CVP and MAP did not rise during the period of observation after it was bled. CONCLUSIONS: The corpus cavernosum is a practical alternative means of intravenous access in the emergency setting in the dog model.
Systemic and splanchnic hemodynamics following hemorrhage and volume restitution with Haemaccel in portal hypertensive rats: the effect of propranolol.
BACKGROUND AND AIMS: Recently, we found in a portal hypertensive rat model that hemorrhage and volume restitution with Haemaccel, a low viscosity plasma expander, induced an increase in cardiac output and portal venous inflow. The present study was conducted to evaluate whether pretreatment with propranolol will attenuate these hyperdynamic changes. METHODS: Portal hypertension was induced by portal vein constriction. Treatment was initiated 14--21 days later. Propranolol (30 mg/kg per day) or water were administered for 7 days via a gastric gavage. Under ketamine anesthesia, 18 h after the last given dose, blood was withdrawn at a constant rate of 0.3 mL/min for 15 min followed by a 15-min stabilization. Haemaccel was infused at the same rate and volume used for withdrawal. Hemodynamic measurements were performed after volume restitution in both groups by using radioactive microspheres. RESULTS: Eight rats were studied in each group. In the propranolol-treated animals, portal venous inflow was decreased (2.4 +/- 0.8 vs 3.8 +/- 0.7 mL/min per 100 g bodyweight; P < 0.01), while splanchnic arteriolar and porto-collateral resistance were increased (52.8 +/- 21.0 vs 32.8 +/- 13.0 and 6.0 +/- 1.4 vs 4.1 +/- 0.7 mmHg x min x 100 g bodyweight/mL; P < 0.05, respectively). Cardiac output, mean arterial pressure, heart rate, total peripheral resistance and portal pressure were not significantly different between the two groups. CONCLUSION: In this model, pretreatment with propranolol prevented the increase in portal venous inflow, which occurs following hemorrhage and volume restitution with Haemaccel. Although caution should be taken in extrapolating data from animal models to humans, our results suggest that volume replacement during a portal hypertensive-related bleeding episode may be safer in a patient treated with non-selective beta-adrenoreceptor antagonists.
Late hemodynamic changes following controlled hemorrhage and volume restitution with blood or Haemaccel in anesthetized portal hypertensive rats.
BACKGROUND AND AIM: In portal hypertensive rats, hemorrhage and acute volume restitution with Haemaccel induced increased cardiac output and portal venous inflow. In the present study, the late hemodynamic effects of this procedure were explored. METHODS: Portal hypertension was induced by portal vein constriction. Blood was withdrawn 11.2 +/- 3.2 days later, at a rate of 0.3 mL/min, for 15 min, followed by 15 min of stabilization. Haemaccel or blood were infused at the same rate and volume used for withdrawal. Hemodynamic measurements were performed after 24 h, using radioactive microspheres. Viscosity was measured with an Ostwald viscometer. Vascular hindrance was calculated as resistance/viscosity ratio. RESULTS: Blood viscosity of the Haemaccel group (n = 11), was lower than in the blood group (n = 11): 2.7 +/- 0.2 versus 4.0 +/- 0.4 (P < 0.01). Arterial pressure, cardiac output, peripheral resistance, portal pressure, portal venous inflow and splanchnic arteriolar resistance were not significantly different. Splanchnic arteriolar and portocollateral hindrance were higher in the Haemaccel group (11.7 +/- 5.3 and 1.5 +/- 0.6 vs 7.7 +/- 3.0 and 0.9 +/- 0.4 mmHg x min x 100 gram body weight/mL, respectively, P < 0.05). CONCLUSION: In portal hypertensive rats, vital organs perfusion, 24 h after hemorrhage and isovolemic volume restitution with Haemaccel and blood, was similar. However, in Haemaccel-transfused animals, a reduction in vascular hindrance, indicating vasoconstriction, was observed in the splanchnic organs, which drain into the portal circulation. Vasoconstriction of the portocollateral vascular bed was observed as well. We suggest that slow-rate volume replacement during a portal-hypertensive-related bleeding episode enables hemodynamic adaptation to occur. Thus, undesirable hyperdynamic changes, which may aggravate secondary bleeding, are attenuated.
Sensorless flow and head estimation in the VentrAssist rotary blood pump.
Flow rate and pressure difference (or head) are key variables needed in the control of implantable rotary blood pumps. However, use of flow and/or pressure probes can decrease reliability and increase system power consumption and expense. For a given fluid viscosity, the flow state is determined by any 2 of the 4 pump variables: Flow, pressure difference, speed, and motor input power can be used. Thus, if viscosity is known or if its influence is sufficiently small, flow rate and pressure difference can be estimated from the motor speed and motor input power. For the VentrAssist centrifugal blood pump, which uses a hydrodynamic bearing, sensorless flow and pressure head estimation accuracy of 2 of our impeller designs were compared for a viscosity range of 1.2 to 4.5 mPas. This showed impeller design optimization can improve estimation accuracy. We also compared estimation accuracy using 2 blood analogues used in vitro, aqueous glycerol and red blood cells suspended in Haemaccel. The nature of the blood analogue and not only the viscosity of the fluid seems to influence estimation accuracy in our pump.
Prospective double-blind randomized study of the effects of four intravenous fluids on platelet function and hemostasis in elective hip surgery.
A prospective randomized double-blind study was performed to determine the effects of three colloids, Haemaccel, Gelofusine and albumin, and also saline on platelet activation, platelet aggregation (induced by adenosine diphosphate (ADP), epinephrine, collagen) platelet agglutination by ristocetin and other hemostatic variables in 55 patients undergoing primary unilateral total hip replacement. The fluids were administered according to normal clinical practice and assessments were made immediately before, at the end, and 2 h after the end of surgery. Surgery was accompanied by thrombin generation (increases in thrombin/antithrombin III complex, prothrombin F1 +2 fragment) platelet activation (betaTG) and compromised coagulation. Generally, the platelet activation appeared to result in platelet desensitization and brought about a persistent reduction in platelet aggregation to ADP and epinephrine, irrespective of the fluid used. Additionally, Haemaccel and Gelofusine inhibited ristocetin-induced platelet agglutination and albumin inhibited collagen-induced platelet aggregation. Gross inhibitory effects of Haemaccel that had been predicted from an earlier in vitro study did not occur. Particular fluids had selective additional effects on the hemostatic system. Albumin infusion served to maintain plasma albumin at normal concentrations postsurgery. The two gelatin preparations, Haemaccel and Gelofusine, maintained plasma viscosity. All three colloids led to a transient increase in activated partial thromboplastin time postsurgery and also a transient fall in the concentration of factor VIII, which were accompanied by a transient increase in bleeding time, but there was no measurable increase in blood loss. Inhibition of platelet aggregation by certain colloids may provide additional protection against the increased thrombotic risk in patients following major surgery.
Augmentation of ultrasound-induced clot disruption by nongas-filled microparticles.
The augmentation of ultrasound-induced clot disruption by echocardiographic contrast microbubbles may be a direct mechanical erosive effect of the clot by the microparticles. To further assess this hypothesis, we evaluated the rate and extent of clot disruption by using external ultrasound and nongas-filled microparticles (HAEMACCEL and HAES). Human blood clots were used in this in vitro study. The percent clot reduction using the combination of ultrasound and microparticles was dose dependent and significantly higher than that with microparticles alone.
Vancomycin interaction with Haemaccel.
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[Immunological studies with Haemaccel].
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[Shock therapy with Haemaccel, a new plasma volume expander].
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[Dilution acidosis in clinical conditions].
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Screening for pulmonary arteriovenous malformations: contrast echocardiography versus pulse oximetry.
Pulmonary arteriovenous malformations (PAVM) cause right-to-left shunt and imply risk of paradoxical embolism and cerebral abscess. These complications can be prevented by appropriate treatment. Detection of PAVMs is therefore important, so simple and reliable screening methods are needed for this purpose. The aim of this investigation was to compare pulse oximetry and contrast echocardiography as screening tools for detection of pulmonary arteriovenous malformations. Eighty-five hereditary haemorrhagic telangiectasia (HHT) patients and first-degree relatives identified in a comprehensive study of HHT-families in the county of Funen, Denmark, were investigated. Standing and supine pulse oximetry in room air was performed in all subjects, and in subjects with symptoms and/or abnormal pulse oximetry in room air, supine pulse oximetry breathing 100% oxygen was also performed. Transthoracic echocardiography with intravenous injection of echo contrast was performed in all subjects. Outcome measures were oxygen saturation change >2% units on changing body position and echo contrast observed in the left-sided heart chambers. Positive contrast echocardiography indicating the presence of PAVM was found in 47 subjects, whereas pulse oximetry was abnormal in only 16. The results strongly suggest that contrast echocardiography is a more sensitive screening tool for PAVMs than pulse oximetry.
Histamine release in human subjects by modified gelatin (Haemaccel) and dextran: an explanation for anaphylactoid reactions observed under clinical conditions?
Histamine release by modified gelatin (Haemaccel) and dextran (Macrodex) has been demonstrated in volunteers by direct and indirect methods. In a pilot study of Haemaccel, histamine release was observed in six of seven volunteers. The highest plasma histamine concentration was 4.8 ng/ml, the lowest 1.7 ng/ml: two of the subjects showed slight allergic reactions. Using Haemaccel batch 2551, 10 out of 12 subjects reacted to the rapid infusion of Haemaccel with increased plasma histamine concentrations, whereas none reacted to Ringer's solution. None of the 10 subjects had an allergic reaction, but an increase in gastric secretion was observed in eight. Changes in the venous basophil granulocyte count were found in both those who reacted and those who did not react to Haemaccel. After the rapid infusion of dextran the highest plasma histamine concentration was 5.0 ng/ml, the lowest 1.3 ng/ml. The withdrawal of blood had no influence on plasma histamine concentration. The incidences of histamine release produced by Haemaccel varied with different batches. Thus, it seems unlikely that immunological mechanisms are principally responsible. Nine instances of allergic and anaphylactoid reactions to plasma substitutes have been reported, seven after Haemaccel infusion, and two after dextran administration. One of the patients who received dextran died. Histamine release was always associated with Haemaccel infusion and corresponded in extent to the clinical symptoms observed, but there was no significant histamine release associated with the reactions to dextran.
Haemodynamic effects of subarachnoid block in elderly patients.
We have studied the haemodynamic effects of subarachnoid block in elderly patients. Thirty patients were undergoing elective transurethral surgery and 18 non-elective orthopaedic surgery, predominantly fractured neck of femur. Systolic arterial pressure (SAP) was measured by automated oscillotonometry, central venous pressure (CVP) by manometer and cardiac index (CI), stroke index (SI) and heart rate (HR) by transthoracic electrical bioimpedance. Systemic vascular resistance index (SVRI) was derived. SAP decreased by more than 25% in 33 patients and SVRI showed similar decreases (P = 0.0001). CVP decreased (2.5 (SD 1.5) cm H2O) in all patients. CI was unaffected because a decrease in SI in some patients (13 (19)%; P = 0.01) was compensated for by an increase in HR (13 (13)%; P = 0.01). Decreases in SAP of 25% were treated initially with colloid solution 8 ml kg-1, which restored SAP in 19 patients. CVP, SI and HR were all restored to baseline values, however, SVRI was decreased further (P < 0.05). Fourteen patients required additional treatment with metaraminol which restored SVRI to baseline values. Patients with systolic hypertension were more likely to require treatment with metaraminol (P = 0.04).
Haemodilution induces a hypercoagulable state.
It has been suggested that haemodilution with saline may increase whole blood coagulation. This study was conducted in two parts. First, we investigated the effect of in vitro dilution of blood with saline on whole blood coagulation as measured by the thrombelastogram (TEG). Blood (4 ml) was diluted with 0.9% saline 1 ml and coagulation compared with that of an undiluted control specimen obtained concurrently from the same subject. In the second part, the study was repeated using a modified gelatin colloidal solution (Haemaccel) as the diluent. The r time, k time and r + k time were decreased relative to control in both diluent groups. The alpha angles were increased compared with control in both groups while maximum amplitude was unchanged in the Haemaccel diluted group. We conclude that haemodilution per se increases the coagulability of whole blood in vitro, but that saline haemodilution has a more marked effect on final clot strength.
Haemodilution induces a hypercoagulable state.
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Effects of gelatin-based resuscitation fluids on platelet aggregation.
Fluid resuscitation aims to maintain intravenous volume without significant effects on haemostasis. Several different types of i.v. fluid are available for use in a patient who has suffered trauma, but there is evidence that some resuscitation fluids may affect primary haemostasis. We have compared the effects of two resuscitation fluids, Haemaccel and Gelofusin, on platelet aggregation in vitro. These resuscitation fluids are both based on gelatin but Haemaccel contains a high concentration of Ca2+ whereas Gelofusin does not. Their effects on platelet aggregation in whole blood, induced by a range of different agents, were determined using a platelet-counting technique. Both Haemaccel and Gelofusin prevented platelet aggregation induced by ristocetin (P < 0.05, Mann-Whitney). In addition, Haemaccel proved to be a potent inhibitor of the platelet aggregation that occurred in response to all of the other agonists investigated: adenosine diphosphate, platelet-activating factor, collagen, a thromboxane A2 mimetic (U46619) and epinephrine. The additional inhibitory effects of Haemaccel were largely, but not completely, attributable to its high Ca2+ content. Inhibition of platelet aggregation by ristocetin may indicate a mechanism by which Haemaccel or Gelofusin may contribute to impaired haemostasis. The presence in Haemaccel of high concentrations of Ca2+, which is largely responsible for inhibition of the aggregation induced by other agents, may provide an additional means by which haemostasis could be impaired.