Carolyn L. Kerr

Effects of a peripheral α2 adrenergic-receptor antagonist on the hemodynamic changes induced by medetomidine administration in conscious dogs

OBJECTIVE To evaluate the effects of administration of a peripheral alpha(2)-adrenergic receptor antagonist (L-659,066), with and without concurrent administration of glycopyrrolate, on cardiopulmonary effects of medetomidine administration in dogs. ANIMALS 6 healthy adult dogs. PROCEDURES Dogs received saline (0.9% NaCl) solution (saline group), L-659,066 (group L), or L-659,066 with glycopyrrolate (group LG). These pretreatments were followed 10 minutes later by administration of medetomidine in a randomized crossover study. Hemodynamic measurements and arterial and mixed-venous blood samples for blood gas analysis were obtained prior to pretreatment, 5 minutes after pretreatment, and after medetomidine administration at intervals up to 60 minutes. RESULTS After pretreatment in the L and LG groups, heart rate, cardiac index, and partial pressure of oxygen in mixed-venous blood (PvO2) values were higher than those in the saline group. After medetomidine administration, heart rate, cardiac index, and PvO2 were higher and systemic vascular resistance, mean arterial blood pressure, and central venous pressure were lower in the L and LG groups than in the saline group. When the L and LG groups were compared, heart rate was greater at 5 minutes after medetomidine administration, mean arterial blood pressure was greater at 5 and 15 minutes after medetomidine administration, and central venous pressure was lower during the 60-minute period after medetomidine administration in the LG group. CONCLUSIONS AND CLINICAL RELEVANCE Administration of L-659,066 prior to administration of medetomidine reduced medetomidine-induced cardiovascular changes in healthy dogs. No advantage was detected with concurrent administration of L-659,066 and glycopyrrolate.

Cardiopulmonary and sedative effects of the peripheral α2-adrenoceptor antagonist MK 0467 administered intravenously or intramuscularly concurrently with medetomidine in dogs

OBJECTIVE To evaluate the cardiopulmonary and sedative effects of the peripheral α(2)-adrenoceptor antagonist MK 0467 when administered IM or IV concurrently with medetomidine in dogs. ANIMALS 8 adult dogs. PROCEDURES Dogs received 20 μg of medetomidine/kg, IM, alone or concurrently with MK 0467 (0.4 mg/kg, IM), and 10 μg of medetomidine/kg, IV, alone or concurrently with MK 0467 (0.2 mg/kg, IV), in a randomized crossover study. Sedation characteristics were scored and hemodynamic measurements and arterial and mixed-venous blood samples for blood gas analysis were obtained before (time 0; baseline) and for 90 minutes after treatment. RESULTS Heart rate (HR), mixed-venous partial pressure of oxygen (Pvo(2)), and cardiac index (CI) were significantly lower and mean arterial blood pressure (MAP), systemic vascular resistance (SVR), and oxygen extraction ratio (ER) were significantly higher after administration of medetomidine IM or IV, compared with baseline values. Administration of medetomidine and MK 0467 IM caused a significantly higher heart rate, CI, and Pvo(2) and significantly lower MAP, SVR, and ER for 60 to 90 minutes than did IM administration of medetomidine alone. Administration of medetomidine and MK 0467 IV caused a significantly higher CI and Pvo(2) and significantly lower MAP, SVR, and ER for 45 to 90 minutes than did IV administration of medetomidine alone. There was no significant difference in sedation scores among treatments. CONCLUSIONS AND CLINICAL RELEVANCE In dogs, MK 0467 administered concurrently with medetomidine IV or IM reduced the cardiovascular effects of medetomidine but had no detectable effect on sedation scores.

Cardiopulmonary effects of anesthetic induction with thiopental, propofol, or a combination of ketamine hydrochloride and diazepam in dogs sedated with a combination of medetomidine and hydromorphone.

OBJECTIVE To evaluate the cardiopulmonary effects of anesthetic induction with thiopental, propofol, or ketamine hydrochloride and diazepam in dogs sedated with medetomidine and hydromorphone. ANIMALS 6 healthy adult dogs. PROCEDURES Dogs received 3 induction regimens in a randomized crossover study. Twenty minutes after sedation with medetomidine (10 microg/kg, IV) and hydromorphone (0.05 mg/kg, IV), anesthesia was induced with ketamine-diazepam, propofol, or thiopental and then maintained with isoflurane in oxygen. Measurements were obtained prior to sedation (baseline), 10 minutes after administration of preanesthetic medications, after induction before receiving oxygen, and after the start of isoflurane-oxygen administration. RESULTS Doses required for induction were 1.25 mg of ketamine/kg with 0.0625 mg of diazepam/kg, 1 mg of propofol/kg, and 2.5 mg of thiopental/kg. After administration of preanesthetic medications, heart rate (HR), cardiac index, and PaO(2) values were significantly lower and mean arterial blood pressure, central venous pressure, and PaCO(2) values were significantly higher than baseline values for all regimens. After induction of anesthesia, compared with postsedation values, HR was greater for ketamine-diazepam and thiopental regimens, whereas PaCO(2) tension was greater and stroke index values were lower for all regimens. After induction, PaO(2) values were significantly lower and HR and cardiac index values significantly higher for the ketamine-diazepam regimen, compared with values for the propofol and thiopental regimens. CONCLUSIONS AND CLINICAL RELEVANCE Medetomidine and hydromorphone caused dramatic hemodynamic alterations, and at the doses used, the 3 induction regimens did not induce important additional cardiovascular alterations. However, administration of supplemental oxygen is recommended.

Effect of synthetic colloid administration on hemodynamic and laboratory variables in healthy dogs and dogs with systemic inflammation.

Objective To compare the effects of administering equal volumes of isotonic crystalloids and synthetic colloids on hemodynamic and laboratory variables in healthy dogs and dogs with systemic inflammation. Design Randomized, placebo-controlled, blinded study. Setting Comparative clinical research facility. Animals Sixteen adult purpose-bred Beagles. Interventions Dogs were first randomized to receive either lipopolysaccharide (LPS; 5 μg/kg, IV) or an equal volume of placebo (0.9% NaCl, IV). Dogs were then randomized into 1 of 2 groups receiving fluid resuscitation with either 40 mL/kg IV isotonic crystalloid (0.9% NaCl) or synthetic colloid (tetrastarch). After a 14-day washout, the study was repeated such that dogs received the opposite treatment (LPS or placebo) and the same resuscitation fluid regimen. Vital signs (heart rate (HR), oscillometric blood pressure) were measured and blood samples were collected for PCV, total plasma protein (TPP), serum lactate concentration, and colloid osmotic pressure (COP) measurements. Measurements and Main Results Healthy (placebo) dogs had similar decreases in PCV and TPP after administration of either fluid. Tetrastarch administration was associated with a larger increase in HR, systolic blood pressure, and mean blood pressure. Dogs with systemic inflammation had similar increases in systolic blood pressure and decreases in PCV, TPP, and lactate after administration of either fluid. Tetrastarch administration caused greater immediate increase in HR and mean blood pressure compared to 0.9% NaCl. In all dogs, 0.9% NaCl administration decreased COP and tetrastarch administration increased COP. Conclusions Resuscitation with equal volumes of 0.9% NaCl and tetrastarch caused similar changes in hemodynamic and laboratory variables in dogs with LPS-induced systemic inflammation; however, larger increases in HR and blood pressure were seen within the first 2 hours following tetrastarch administration compared to 0.9% NaCl. Tetrastarch administration increased COP in all dogs, despite a decrease in TPP.OBJECTIVE To compare the effects of administering equal volumes of isotonic crystalloids and synthetic colloids on hemodynamic and laboratory variables in healthy dogs and dogs with systemic inflammation. DESIGN Randomized, placebo-controlled, blinded study. SETTING Comparative clinical research facility. ANIMALS Sixteen adult purpose-bred Beagles. INTERVENTIONS Dogs were first randomized to receive either lipopolysaccharide (LPS; 5 μg/kg, IV) or an equal volume of placebo (0.9% NaCl, IV). Dogs were then randomized into 1 of 2 groups receiving fluid resuscitation with either 40 mL/kg IV isotonic crystalloid (0.9% NaCl) or synthetic colloid (tetrastarch). After a 14-day washout, the study was repeated such that dogs received the opposite treatment (LPS or placebo) and the same resuscitation fluid regimen. Vital signs (heart rate (HR), oscillometric blood pressure) were measured and blood samples were collected for PCV, total plasma protein (TPP), serum lactate concentration, and colloid osmotic pressure (COP) measurements. MEASUREMENTS AND MAIN RESULTS Healthy (placebo) dogs had similar decreases in PCV and TPP after administration of either fluid. Tetrastarch administration was associated with a larger increase in HR, systolic blood pressure, and mean blood pressure. Dogs with systemic inflammation had similar increases in systolic blood pressure and decreases in PCV, TPP, and lactate after administration of either fluid. Tetrastarch administration caused greater immediate increase in HR and mean blood pressure compared to 0.9% NaCl. In all dogs, 0.9% NaCl administration decreased COP and tetrastarch administration increased COP. CONCLUSIONS Resuscitation with equal volumes of 0.9% NaCl and tetrastarch caused similar changes in hemodynamic and laboratory variables in dogs with LPS-induced systemic inflammation; however, larger increases in HR and blood pressure were seen within the first 2 hours following tetrastarch administration compared to 0.9% NaCl. Tetrastarch administration increased COP in all dogs, despite a decrease in TPP.

The cardiopulmonary effects of anesthetic induction with isoflurane, ketamine-diazepam or propofol-diazepam in the hypovolemic dog.

OBJECTIVE To evaluate and compare the cardiopulmonary effects of induction of anesthesia with isoflurane (Iso), ketamine-diazepam (KD), or propofol-diazepam (PD) in hypovolemic dogs. Study design Prospective randomized cross-over trial. ANIMALS Six healthy intact, mixed breed, female dogs weighing 20.7 +/- 4.2 kg and aged 22 +/- 2 months. Methods Dogs had 30 mL kg(-1) of blood removed at a rate of 1.5 mL kg(-1) minute(-1) under isoflurane anesthesia. Following a 30-minute recovery period, anesthesia was reinduced. Dogs were assigned to one of three treatments: isoflurane via facemask using 0.5% incremental increases in the delivered concentration every 30 seconds, 1.25 mg kg(-1) ketamine and 0.0625 mg kg(-1) diazepam intravenously (IV) with doses repeated every 30 seconds as required, and 2 mg kg(-1) propofol and 0.2 mg kg(-1) diazepam IV followed by 1 mg kg(-1) propofol increments IV every 30 seconds as required. Following endotracheal intubation all dogs received 1.7% end-tidal isoflurane in oxygen. Cardiopulmonary variables were recorded at baseline (before induction) and at 5 or 10 minute intervals following endotracheal intubation. RESULTS Induction time was longer in Iso (4.98 +/- 0.47 minutes) compared to KD (3.10 +/- 0.47 minutes) or PD (3.22 +/- 0.45 minutes). To produce anesthesia, KD received 4.9 +/- 2.3 mg kg(-1) ketamine and 0.24 +/- 0.1 mg kg(-1) diazepam, while PD received 2.2 +/- 0.4 mg kg(-1) propofol and 0.2 mg kg(-1) diazepam. End-tidal isoflurane concentration immediately following intubation was 1.7 +/- 0.4% in Iso. Arterial blood pressure and heart rate were significantly higher in KD and PD compared to Iso and in KD compared to PD. Arterial carbon dioxide partial pressure was significantly higher in PD compared to KD and Iso immediately after induction. CONCLUSIONS AND CLINICAL RELEVANCE In hypovolemic dogs, KD or PD, as used in this study to induce anesthesia, resulted in less hemodynamic depression compared to isoflurane.

Evaluation of the efficacy and safety for use of two sedation and analgesia protocols to facilitate assisted ventilation of healthy dogs.

OBJECTIVE To determine the effectiveness and safety of 2 sedative-analgesic protocols to facilitate assisted ventilation in healthy dogs. ANIMALS 12 healthy dogs. PROCEDURES Dogs were randomly assigned to 2 groups. Mean dosages for protocol 1 were diazepam (0.5 mg/kg/h [n = 3 dogs]) or midazolam (0.5 mg/kg/h [3]), morphine (0.6 mg/kg/h [6]), and medetomidine (1.0 microg/kg/h [6]). Mean dosages for protocol 2 were diazepam (0.5 mg/kg/h [n = 3]) or midazolam (0.5 mg/kg/h [3]), fentanyl (18 microg/kg/h [6]), and propofol (2.5 mg/kg/h [6]). Each dog received the drugs for 24 consecutive hours. All dogs were mechanically ventilated with adjustments in minute volume to maintain normocapnia and normoxemia. Cardiorespiratory variables were recorded. A numeric comfort score was assigned hourly to assess efficacy. Mouth care, position change, and physiotherapy were performed every 6 hours. Urine output was measured every 4 hours. RESULTS Use of both protocols maintained dogs within optimal comfort ranges > 85% of the time. The first dog in each group was excluded from the study. Significant decreases in heart rate, oxygen consumption, and oxygen extraction ratio were evident for protocol 1. Cardiac index values in ventilated dogs were lower than values reported for healthy unsedated dogs. Oxygen delivery, lactate concentration, and arterial base excess remained within reference ranges for both protocols. CONCLUSIONS AND CLINICAL RELEVANCE Use of both protocols was effective for facilitating mechanical ventilation. A reduction in cardiac index was detected for both protocols as a result of bradycardia. However, oxygen delivery and global tissue perfusion were not negatively affected.

Cardiopulmonary effects of intravenous fentanyl infusion in dogs during isoflurane anesthesia and with concurrent acepromazine or dexmedetomidine administration during anesthetic recovery

OBJECTIVE To evaluate the cardiopulmonary effects of IV fentanyl administration in dogs during isoflurane anesthesia and during anesthetic recovery with or without dexmedetomidine or acepromazine. ANIMALS 7 sexually intact male purpose-bred hound-type dogs aged 11 to 12 months. PROCEDURES Dogs received a loading dose of fentanyl (5 μg/kg, IV) followed by an IV infusion (5 μg/kg/h) for 120 minutes while anesthetized with isoflurane and for an additional 60 minutes after anesthesia was discontinued. Dogs were randomly assigned in a crossover design to receive dexmedetomidine (2.5 μg/kg), acepromazine (0.05 mg/kg), or saline (0.9% NaCl) solution (1 mL) IV after anesthesia ceased. Cardiopulmonary data were obtained during anesthesia and for 90 minutes after treatment administration during anesthetic recovery. RESULTS Concurrent administration of fentanyl and isoflurane resulted in significant decreases in mean arterial blood pressure, heart rate, and cardiac index and a significant increase in Paco2. All but Paco2 returned to pretreatment values before isoflurane anesthesia was discontinued. During recovery, dexmedetomidine administration resulted in significant decreases in heart rate, cardiac index, and mixed venous oxygen tension and a significant increase in arterial blood pressure, compared with values for saline solution and acepromazine treatments. Acepromazine administration resulted in significantly lower blood pressure and higher cardiac index and Po2 in mixed venous blood than did the other treatments. Dexmedetomidine treatment resulted in significantly lower values for Pao2 and arterial pH and higher Paco2 values than both other treatments. CONCLUSIONS AND CLINICAL RELEVANCE Fentanyl resulted in transient pronounced cardiorespiratory effects when administered during isoflurane anesthesia. During anesthetic recovery, when administered concurrently with an IV fentanyl infusion, dexmedetomidine resulted in evidence of cardiopulmonary compromise and acepromazine transiently improved cardiopulmonary performance.

A comparison of 3 anesthetic protocols for 24 hours of mechanical ventilation in cats

Objective To compare the recovery times, recovery quality, and cardiovascular (CV) effects of 3 anesthetic protocols during 24 hours of mechanical ventilation (MV) in healthy cats. Design Prospective, randomized, crossover study. Setting Research laboratory at a veterinary teaching hospital. Animals Six healthy intact male purpose-bred cats. Interventions Each cat was randomly assigned to receive 3 anesthetic protocols for 24 hours of MV; Protocol K consisted of ketamine, Protocol P, propofol; and Protocol PK, propofol plus fixed-rate low-dose ketamine. Each infusion drug dose was adjusted using a sedation scoring system. All protocols included fixed doses of fentanyl (10 μg/kg/h) and midazolam (0.5 mg/kg/h). Measurements and Main Results Drug doses and recovery times were recorded. Recovery quality was scored. Blood gas results, CV parameters, and frequency of bradycardia or hypotension requiring interventions were recorded. The mean d dose ± standard error of K was 81.3 ± 3.3 μg/kg/m. The median dose (95% cardiac index) of propofol (μg/kg/m) in PK was 16.0 (13.1, 19.6) and in P was 48.1 (39.3, 58.9). P necessitated significantly more propofol than PK (P < 0.05). Protocol K (35.6 ± 3.2 hours) had significantly longer times to full recovery compared to P (18.2 ± 3.2 hours). Protocol K had significantly longer times to head up, crawling, and standing compared to P and PK. Cats sedated with PK (2.33 ± 0.47) required significantly more interventions for hypotension than K (0.50 ± 0.47). Protocol P (3.2 ± 0.4) and PK (1.4 ± 0.3) required significantly more interventions for bradycardia compared to K (0.8 ± 0.3). When comparing protocol K to P and PK, significant differences in blood pressure, lactate, oxygen delivery, and oxygen consumption were noted. Conclusions Cats anesthetized with P had shorter times to full recovery compared to K. Cats anesthetized with K required fewer interventions for bradycardia or hypotension but had longer recovery times compared to P or PK. Protocol PK reduced the propofol dose required to maintain optimal anesthesia.OBJECTIVE To compare the recovery times, recovery quality, and cardiovascular (CV) effects of 3 anesthetic protocols during 24 hours of mechanical ventilation (MV) in healthy cats. DESIGN Prospective, randomized, crossover study. SETTING Research laboratory at a veterinary teaching hospital. ANIMALS Six healthy intact male purpose-bred cats. INTERVENTIONS Each cat was randomly assigned to receive 3 anesthetic protocols for 24 hours of MV; Protocol K consisted of ketamine, Protocol P, propofol; and Protocol PK, propofol plus fixed-rate low-dose ketamine. Each infusion drug dose was adjusted using a sedation scoring system. All protocols included fixed doses of fentanyl (10 μg/kg/h) and midazolam (0.5 mg/kg/h). MEASUREMENTS AND MAIN RESULTS Drug doses and recovery times were recorded. Recovery quality was scored. Blood gas results, CV parameters, and frequency of bradycardia or hypotension requiring interventions were recorded. The mean d dose ± standard error of K was 81.3 ± 3.3 μg/kg/m. The median dose (95% cardiac index) of propofol (μg/kg/m) in PK was 16.0 (13.1, 19.6) and in P was 48.1 (39.3, 58.9). P necessitated significantly more propofol than PK (P < 0.05). Protocol K (35.6 ± 3.2 hours) had significantly longer times to full recovery compared to P (18.2 ± 3.2 hours). Protocol K had significantly longer times to head up, crawling, and standing compared to P and PK. Cats sedated with PK (2.33 ± 0.47) required significantly more interventions for hypotension than K (0.50 ± 0.47). Protocol P (3.2 ± 0.4) and PK (1.4 ± 0.3) required significantly more interventions for bradycardia compared to K (0.8 ± 0.3). When comparing protocol K to P and PK, significant differences in blood pressure, lactate, oxygen delivery, and oxygen consumption were noted. CONCLUSIONS Cats anesthetized with P had shorter times to full recovery compared to K. Cats anesthetized with K required fewer interventions for bradycardia or hypotension but had longer recovery times compared to P or PK. Protocol PK reduced the propofol dose required to maintain optimal anesthesia.

Investigation of the use of three electroencephalographic electrodes for long-term electroencephalographic recording in awake and sedated dogs

OBJECTIVE To compare electroencephalography (EEG) artifact associated with use of the subdermal wire electrode (SWE), gold cup electrode (GCE), and subdermal needle electrode (SNE) over an 8-hour period in sedated and awake dogs. ANIMALS 6 healthy dogs. PROCEDURES 8 EEG channels were recorded during 20-minute video-EEG recording sessions (intermittently at 0.5, 2, 4, 6, and 8 hours) with and without chlorpromazine sedation. Nonphysiologic artifacts were identified. Duration of artifact was summed for each channel. Number of unaffected channels (NUC) was determined. RESULTS NUC was significantly affected by electrode type and sedation over time; median for SWE (2.80 channels; 95% confidence interval [CI], 0.84 to 5.70 channels) was significantly different from medians for GCE (7.87 channels; 95% CI, 7.44 to 7.94 channels) and SNE (7.60 channels; 95% CI, 6.61 to 7.89 channels). After 4 hours, NUC decreased in awake dogs, regardless of electrode type. In awake dogs, duration of artifact differed significantly between SWE and GCE or SNE; medians at 8 hours were 61.55 seconds (95% CI, 21.81 to 173.65 seconds), 1.33 seconds (95% CI, 0.47 to 3.75 seconds), and 21.01 seconds (95% CI, 6.85 to 64.42 seconds), respectively. CONCLUSIONS AND CLINICAL RELEVANCE The SWE had a significant duration of artifact during recording periods > 2 hours, compared with results for the GCE and SNE, in awake dogs. The GCE, SNE, and sedation resulted in significantly more channels unaffected by artifact. For longer recordings, caution should be exercised in selecting EEG electrodes and sedation state, although differences among electrodes may not be clinically relevant.

Effect of Synthetic Colloid Administration on Coagulation in Healthy Dogs and Dogs with Systemic Inflammation

Background Synthetic colloids are often used during fluid resuscitation and affect coagulation. Objective To compare the effects of an isotonic crystalloid and synthetic colloid on coagulation in healthy dogs and dogs with systemic inflammation. Animals Sixteen adult purpose‐bred Beagles. Methods Randomized, placebo‐controlled, blinded study. Dogs were randomized into one of two groups receiving fluid resuscitation with either 40 mL/kg IV 0.9% NaCl or tetrastarch after administration of lipopolysaccharide or an equal volume of placebo. After a 14‐day washout period, the study was repeated such that dogs received the opposite treatment (LPS or placebo) but the same resuscitation fluid. Blood samples were collected at 0, 1, 2, 4, and 24 hours for measurement of coagulation variables. Results Administration of either fluid to healthy dogs and dogs with systemic inflammation resulted in similar increases in prothrombin time and activated clotting time. In comparison to saline administration, tetrastarch administration resulted in significantly decreased R (P = .017) in healthy dogs, as well as significantly increased activated partial thromboplastin time (P ≤ .016), CL30% (P ≤ .016), and K (P < .001) and significantly decreased platelet count (P = .019), α (P ≤ .001), MA (P < .001), and von Willebrand factor antigen (P < .001) and collagen binding activity (P ≤ .003) in both healthy dogs and dogs with systemic inflammation. Conclusions and Clinical Importance Tetrastarch bolus administration to dogs with systemic inflammation resulted in a transient hypocoagulability characterized by a prolonged activated partial thromboplastin time, decreased clot formation speed and clot strength, and acquired type 1 von Willebrand disease.