The effects of lactated Ringer's solution (LRS) or LRS and 6% hetastarch on the colloid osmotic pressure, total protein and osmolality in healthy horses under general anesthesia

ObjectiveTo investigate changes in colloid osmotic pressure (COP), total protein (TP) and osmolality (OSM) during anesthesia in horses given intravenous lactated Ringer’s solution (LRS) or LRS and hetastarch (HES).Study designProspective, clinical trial.AnimalsFourteen horses presented for surgery. Mean age 8.3 ± 1.9 years; mean weight 452 ± 25 kg.MethodsHorses were premedicated with xylazine intravenously (IV); anesthesia was induced with ketamine and diazepam IV, and maintained with sevoflurane. Butorphanol was administered IV with pre-medications or immediately after induction. Xylazine was administered IV for recovery if necessary. LRS was administered IV to all horses with a target rate of 5–10 mL kg^?1 hour^?1. Half of the horses also received 6% HES, 2.5 mL kg^?1 over 1 hour in addition to LRS. Horses that received LRS only were considered the LRS group. Horses that received both LRS and HES were considered the LRS/HES group. Blood was drawn pre- and post-anesthesia, immediately following induction, and every 30 minutes throughout anesthesia. COP, TP and OSM were measured.ResultsCOP and TP significantly decreased at similar rates for both treatment groups from pre-anesthetic values. Pre-anesthetic COP was significantly greater in the LRS group when compared to the LRS/HES group pre-, post- and throughout anesthesia. In the LRS group post-anesthetic OSM was significantly different than the pre-anesthesia value and that for the LRS/HES group.Conclusions and clinical relevanceAdministration of IV HES (2.5 mL kg^?1, over 1 hour) in combination with LRS does not attenuate the decrease in COP typically seen during anesthesia with crystalloid administration alone. Based on these results, administration of HES at this rate and total volume would not be expected to prevent fluid shifts into the interstitium through its effects on COP.     

Changes in colloid osmotic pressure as a function of anesthesia and surgery in the presence and absence of isotonic fluid administration in dogs

Objective  To determine how a combination of anesthetic drugs; including pre-medication, induction agents and inhalational agents; affect colloid osmotic pressure (COP) in the presence and absence of isotonic fluid administration. Secondarily, to determine if changes in total plasma protein (TPP) correlate with COP in anesthetized patients.
Study Design  Prospective, randomized clinical study.
Animals  Ten female dogs, 4 months to 4 years of age and >8 kg undergoing elective ovariohysterectomy.
Methods  All dogs were anesthetized in a similar fashion. After induction, five dogs received lactated ringer's solution (LRS) at 10 mL kg⁻¹ hour⁻¹ and five dogs received no fluid therapy during anesthesia. Blood samples were collected prior to pre-medication, prior to induction, immediately post-induction/prior to the inhalational agent, 30 minutes post-induction, at the time of recovery and 45 minutes post-discontinuation of inhalant. TPP and COP were measured from each sample.
Results  Administration of fluids resulted in a decrease in COP and TPP over time that did not return to baseline by 45 minutes after recovery. Anesthesia without the administration of fluids also resulted in a significant decrease in COP over time, that was rebounding by recovery (but still significantly less than baseline). TPP had variable correlation with COP at different time points with or without fluid administration.
Conclusions and clinical relevance  Anesthetic drugs alter COP similarly in the presence and absence of isotonic fluids. These changes in COP did not have a simple relationship to TPP and so the latter could not be used to predict COP in this patient population.     

Comparison of the effect of hypertonic hydroxyethyl starch and mannitol on the intraocular pressure in healthy normotensive dogs and the effect of hypertonic hydroxyethyl starch on the intraocular pressure in dogs with primary glaucoma

PURPOSE: The purpose of this study was to determine if intravenous hypertonic hydroxyethyl starch (7.5%/6%) (HES) could decrease the intraocular pressure (IOP) in healthy normotensive dogs, and compare its effect with that of mannitol (20%) (experimental study). In addition, the potential IOP-lowering effect of hypertonic HES was evaluated in six dogs with primary glaucoma (clinical study). MATERIAL AND METHODS: Experimental study: eight male ophthalmoscopically and clinically healthy Beagles were included in this study. The IOP of each dog was measured by applanation tonometry in both eyes to obtain control values at 10:00, 10:15, 10:30, 10:45, 11:00 a.m., and then every hour until 6:00 p.m. prior to the first treatment (control period). Each dog received, with at least 2-week intervals and in a random order, an intravenous (IV) infusion of 4 mL/kg hypertonic HES (1.2 g/kg NaCl; 0.96 g/kg HES) and 4 mL/kg mannitol 20% (1 g/kg) over a period of 15 min starting at 10:00 a.m. IOP was measured oculus uterque (OU) at the same time intervals as in the control study. The differences in IOP between the treatment groups and the baseline IOP (before the start of infusion), between oculus sinister (OS) and oculus dexter (OD) and between the same time points of all groups were determined with a Student's t-test for paired samples (P = 0.05). Clinical study: six dogs with primary glaucoma (representing seven eyes) received an IV infusion of 4 mL/kg hypertonic HES over a period of 15 min. IOP was measured before and 15 and 30 min after starting the infusion. RESULTS: Experimental study: no significant difference between IOP of both eyes was found. A significant decrease in IOP from baseline value was recorded at 15, 30, 45, and 60 min after the start of mannitol infusion (mean amplitude in IOP decrease 3.21 mmHg; P < 0.05) and at 15 and 30 min in dogs treated with HES (mean amplitude in IOP decrease 2.43 mmHg; P < 0.05). At 120 and 180 min there was a significantly higher IOP (P < 0.05) in HES treatment group compared to the values of the control group. Clinical study: in 5/7 eyes diagnosed with primary glaucoma a maximum decrease in IOP of an average of 24% from the baseline value (IOP before start of the infusion) was observed (range of decrease 2-21 mmHg). In three of these five cases the maximum decrease was reached at 15 min and in two cases at 30 min. In one case an increase in IOP of 35% (+ 18 mmHg) was seen after 15 min and 26% (+ 13 mmHg) after 30 min. Case 4 showed an increase in IOP of 5% (+ 3 mmHg) after 15 min and a decrease of 6% (- 4 mmHg) after 30 min. CONCLUSIONS: Intravenous hypertonic HES is comparable to intravenous mannitol 20% in lowering the intraocular pressure in healthy normotensive dogs. But this effect lasted half an hour longer after mannitol. In 6/7 eyes with primary glaucoma, hypertonic HES decreased IOP.     

Evaluation of biomarkers of kidney injury following 4% succinylated gelatin and 6% hydroxyethyl starch 130/0.4 administration in a canine hemorrhagic shock model

Objective : To investigate the association between synthetic colloids and biomarkers of acute kidney injury (AKI) in dogs with hemorrhagic shock. Design : Experimental interventional study. Setting : University. Animals : Twenty‐four healthy ex‐racing Greyhounds. Interventions : Anesthetized Greyhounds subjected to hemorrhage for 60 min were resuscitated with 20 mL/kg of fresh whole blood (FWB), 6% hydroxyethyl starch (HES) 130/0.4, 4% succinylated gelatin (GELO), or 80 mL/kg of isotonic crystalloid (CRYST) over 20 min (n = 6 per treatment). Concentrations of biomarkers of AKI were measured at baseline, end of hemorrhage, and at 40 (T60), 100 (T120), and 160 (T180) min after fluid bolus. Biomarkers included neutrophil gelatinase‐associated lipocalin in urine and serum (uNGAL; sNGAL), and urine cystatin C (uCYSC), kidney injury molecule‐1 (uKIM), clusterin (uCLUST), osteopontin, gamma‐glutamyl transferase, monocyte chemoattractant protein‐1 (uMCP), interleukin‐6, interleukin‐8, protein (uPROT), hyaluronan, and F₂‐isoprostanes. Renal histology was scored for tubular injury and microvesiculation. Biomarker fold‐change from baseline was compared between groups using mixed effects models (Bonferroni–Holm corrected P<0.05). Frequencies of histology scores were compared by Fisher's exact test. Measurements and main results : In dogs treated with GELO, uNGAL fold‐change was markedly greater compared with all other groups at T60, T120, and T180 (all P<0.001), and uCYSC was greater at T60 compared with CRYST (P<0.001), and at T120 and T180 compared with all other groups (all P<0.001). Smaller, albeit significant, between‐group differences in uKIM, uCLUST, uMCP, and urine protein concentration were observed across the FWB, GELO, and HES groups, compared with CRYST. The GELO group more frequently had marked tubular microvesiculation than the other groups (P = 0.015) although tubular injury scores were comparable. Conclusion : In dogs with hemorrhagic shock, GELO was associated with greater magnitude increases in urine biomarkers of AKI and more frequent marked tubular microvesiculation, compared with FWB, CRYST, and HES.     

The effects of 10% hypertonic saline, 0.9% saline and hydroxy ethyl starch infusions on hydro-electrolyte status and adrenal function in healthy conscious dogs

The purpose of this study was to investigate the influence of different saline and colloid solutions on adrenal steroid secretion in dogs. Six healthy male Beagles underwent three infusion cycles: 10 min infusion of 30 ml/kg of NaCl 0.9%, 5 ml/kg of hydroxy ethyl starch, or 5 ml/kg of NaCl 10%. Plasma osmolality, hematocrit, total solids, cortisol and aldosterone levels were measured at 0, 5, 15, 30, 60, 120, 180 and 240 min after beginning infusion. Plasma ACTH levels were measured at 0, 15 and 240 min. An identical timing of sampling was applied during a control session omitting the fluid infusion. Osmolality, sodium, chloride and cortisol levels were found to be significantly higher with hypertonic saline solute compared to control. All fluid infusions lead to lowered plasma potassium, hematocrit, total solids and aldosterone values. ACTH concentrations did not show significant changes with any of the infusion cycles. The increase in cortisol levels suggests that hypertonic saline infusion could be interesting in critical care resuscitation, particularly in patients who are suffering from relative adrenal insufficiency.     

A comparison of the antinociceptive effects of xylazine, detomidine and romifidine on experimental pain in horses

Objective To study the analgesic potency of the α₂‐agonist romifidine in the horse using both an electrical current and a mechanical pressure model for nociceptive threshold testing. In addition, a comparison was made with doses of detomidine and xylazine that produce equivalent degrees of sedation. Study design Randomized, placebo‐controlled, blinded cross‐over study. Animals Six adult Swiss warmblood horses, one mare and five geldings, weighing from 530 to 650 kg and aged 6–15 years. Methods Nociceptive thresholds were measured using an electrical stimulus applied to the coronary band and using a pneumatically operated pin pressing on the cannon bone. Measurements were made immediately before and every 15 minutes for 2 hours after IV injection of the test substances. Lifting of the foot indicated the test end point. Results The three α₂‐agonists caused a temporary increase in nociceptive thresholds with a maximal effect within 15 minutes and a return to baseline levels within 1 hour. Using electrical current testing nociceptive thresholds were significantly different from placebo (mean ± SD) for detomidine at 15 minutes (from control 5.8 ± 0.9 to 23.3 ± 3.9 mA, p = 0.0066) and 30 minutes (from control 6.6 ± 1.1 to 18.8 ± 3.3 mA, p = 0.0091). The difference was significant for romifidine at 15 minutes only (from control 5.8 ± 0.9 to 18.7 ± 3.8 mA, p = 0.0066). With mechanical pressure testing nociceptive thresholds were significantly different from control for detomidine at 15 minutes (from 3.2 ± 0.2 to 6.2 ± 0.5 N, p = 0.00076) and 30 minutes (from 3.2 ± 0.7 to 5.7 ± 0.8 N, p = 0.0167). The difference was significant for xylazine at 15 minutes (from control 3.2 ± 0.2 to 5.6 ± 0.7 N, p = 0.0079). At 15 minutes the order of magnitude of the measured antinociceptive effect was significantly different between the two pain tests for both romifidine and detomidine, but not for xylazine. For romifidine, the increase of mean thresholds compared to placebo was 4.0 ± 1.3 times placebo levels with the electrical current test compared to 1.3 ± 0.3 times for the mechanical pressure test (p = 0.037). For detomidine, the increase of mean thresholds compared to placebo was 5.4 ± 1.7 times control levels with the electrical current test compared to 2.0 ± 0.2 times for the mechanical pressure test (p = 0.040). This represents a 2.7 (romifidine) and 3.4 times (detomidine) greater increase in thresholds using electrical current testing compared to the use of mechanical pressure testing. Conclusion and clinical relevance This study demonstrates the analgesic potential of α₂‐agonists in the horse for somatic pain and that they can have quantitatively different antinociceptive effects according to the antinociceptive test used.     

Effects of isovolemic resuscitation with hemoglobin-based oxygen carrier Hemoglobin glutamer-200 (bovine) on systemic and mesenteric perfusion and oxygenation in a canine model of hemorrhagic shock: a comparison with 6% hetastarch solution and shed blood

OBJECTIVE: To study Hemoglobin glutamer-200 bovine (Hb-200), 6% hetastarch (HES) and shed whole blood (WB) resuscitation in canine hemorrhagic shock. STUDY DESIGN: Prospective laboratory investigation. Animals Twelve adult dogs [29 +/- 1 kg (mean +/- SD)]. METHODS: Anesthetized dogs were instrumented for recording systemic and mesenteric hemodynamic parameters and withdrawal of arterial, mixed and mesenteric venous blood, in which hematological, oxygenation, blood gas and acid-bases variables were determined. Recordings were made before [baseline (BL)], after 1 hour of hypovolemia and immediately and 3 hours post-resuscitation with 30 mL kg(-1) of either Hb-200, HES, or WB. RESULTS: Blood withdrawal (average 34 +/- 2 mL kg(-1)) caused significant hemodynamic changes, metabolic acidosis and hyperlactatemia characteristic for hemorrhagic shock. Only WB transfusion restored all variables. Hemoglobin glutamer-200 bovine infusion returned most hemodynamic parameters including cardiac output and mesenteric arterial blood flow to BL but increased mean arterial pressure above BL (p < 0.05). However, Hb-200 failed to restore total Hb and arterial oxygen content (CaO2), leaving systemic (DO2I) and mesenteric O2 delivery (DO2Im) below BL (p < 0.05). Nevertheless, acid-base variables recovered completely after Hb-200 resuscitation, and met-hemoglobin (Met-Hb) levels increased (p < 0.05). Hetastarch resuscitation returned hemodynamic variables to or above BL but further decreased total Hb and CaO2, preventing recovery of sDO2I and mDO2I (p < 0.05). Thus, systemic and mesenteric O2 extraction stayed above BL (p < 0.05) while acid-base variables recovered to BL, although slower than in Hb-200 and WB groups (p < 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: Resuscitation with Hb-200 seemed to resolve metabolic acidosis and lactatemia more rapidly than HES, but not WB; yet it is not superior to HES in improving DO2I and DO2Im. The hyperoncotic property of solutions like Hb-200 that results in rapid volume expansion with more homogenous microvascular perfusion and the ability to facilitate diffusive O2 transfer accelerating metabolic recovery may be the key mechanisms underlying their beneficial effects as resuscitants.     

A comparison of the effects of hydromorphone HCl and a novel extended release hydromorphone on arterial blood gas values in conscious healthy dogs

The purpose of this study was to evaluate arterial blood gases in dogs that were given hydromorphone or extended release liposome-encapsulated hydromorphone (LEH). Dogs were randomly administered LEH, n = 6, (2.0 mg kg⁻¹), hydromorphone, n = 6, (0.2 mg kg⁻¹) or a placebo of blank liposomes, n = 3, subcutaneously on separate occasions. Arterial blood samples were drawn at serial time points over a 6-h time period for blood gas analysis. There was no change from baseline values in P_aCO₂, P_aO₂, (HCO₃-), pH, and SBEc in the dogs that received the placebo. Administration of hydromorphone resulted in significant increases in P_aCO₂ (maximum (mean + SD] 44.4 + 1.1 mm of Hg) and significant decreases in P_aO₂ (minimum (mean + SD) 82.4 + 4.7 mm of Hg) and pH (minimum (mean + SD) 7.31 + 0.01) compared with baseline. Administration of LEH resulted in significant increases in P_aCO₂ (maximum (mean + SD) 44.6 + 0.9 mm of Hg) and significant decreases in P_aO₂ (minimum (mean + SD) 84.8 + 2.6 mm of Hg) and pH (minimum (mean + SD) 7.34 + 0.02) compared with baseline. There was no significant difference between these two groups at any time point. The changes observed in P_aCO₂, P_aO₂, and pH, however, were within clinically acceptable limits for healthy dogs. LEH was determined to cause moderate changes in arterial blood gas values similar to those caused by hydromorphone.     

A comparison of the mitogenic effects of a phorbol ester on lymphocytes from bovine spleen,lymph node and peripheral bloodComparaison des effets mitogenes d'un ester de phorbol sur des lymphocytes bovins de rate,de ganglions lymphatiques et de sang peripherique

A comparison of the mitogenic effects of a phorbol ester on lymphocytes from bovine spleen, lymph node and peripheral blood.Bovine lymphocytes from three tissues, lymph node, spleen and peripheral blood were compared for their mitogenic responses to 12-O-tetraecanoylphorbol-13-acetate (TPA), a phorbol ester tumor promoter. TPA alone was found to be either not mitogenic or caused only a weak response when compared with the mitogenic lectin phytohemagglutinin (PHA). Of the three lymphocyte preparations, blood cells showed the greatest proliferative response to TPA. However, all three, lymph node, blood and spleen cells, showed a co-mitogenic response to TPA. That is, TPA synergistically enhanced DNA synthesis in cells stimulated with a suboptimal concentration of PHA.