<div><b>Background:</b> Bradycardia and hypotension are complications commonly occurring during general anesthesia in small animals. Intraoperative hypotension has been found to be associated with adverse postoperative consequences. </div><div><br></div><div><b>Objectives: </b>The objectives of his study were first, to determine the incidence of bradycardia, hypotension, and bradycardia with hypotension in dogs undergoing general anesthesia, and second, to identify the risk factors associated with these three complications. The third objective was to evaluate the relationship between these three intraoperative complications and the recovery quality in these dogs.</div><div><br></div><div><b>Methods and Materials:</b> A retrospective cohort study was performed using anesthetic records from 250 dogs undergoing general anesthesia between May 23, 2018 and October 1, 2018 at the Purdue University Veterinary Teaching Hospital. Intraoperative bradycardia was defined as heart rate < 60 beats/min for at least two consecutive readings at 5 minutes apart. Hypotension was defined as mean arterial pressure (MAP) < 60 mmHg or a systolic arterial pressure (SAP) < 80 mmHg for at least two consecutive readings. A univariate analysis followed by multiple logistic regression was performed to build the model for bradycardia, hypotension, and bradycardia with hypotension. The relationships between the three complications and the recovery quality were analyzed using the Pearson’s chi-square test.</div><div><br></div><div><b>Results:</b> The study found that out of the 250 dogs, 114 (45.6%) developed bradycardia, 113 (45.2%) developed hypotension, and 32 (12.8%) dogs developed bradycardia with hypotension. The use of dexmedetomidine-based tranquilizers/sedatives, longer duration of anesthesia, and subjection to orthopedic and neurologic surgical procedures were all identified as risk factors for the dogs to develop bradycardia. The use of acepromazine-based tranquilizers/sedatives, young and old age dogs, and dogs subjected to neurologic surgery were associated with the development of intraoperative hypotension. When the length of the anesthesia increased, the chance for developing bradycardia with hypotension increased. There was no significant association between these intraoperative complications and the recovery quality.</div><div><b><br></b></div><div><b>Conclusions:</b> We found a high incidence of bradycardia or hypotension while a much lower incidence of bradycardia with hypotension in the anesthetized dogs. The risk factors for bradycardia were the use of dexmedetomidine-based tranquilizers/sedatives, the longer duration of anesthesia, and the performance of orthopedic surgery and neurosurgery. The risk factors for hypotension included the use of acepromazine-based tranquilizers/sedatives, the older or younger age of dogs, and the performance of neurosurgery. The risk factor for bradycardia with hypotension was the longer duration of anesthesia. While these adverse events developed intraoperatively, we could not identify a direct influence of these complications on the recovery quality. </div><div><br></div>

<p>Neuropathic pain of central and peripheral origin presents a substantial clinical problem as it is often resistant to pharmacological treatment.</p><p>The health related quality of life of 126 patients with peripheral neuropathic pain was studied, to provide a cross sectional description from this point of view. Two generic health-related quality of life instruments; the SF-36 and the Nottingham Health Profile were used together with pain assessments, global rating of health and verbal rating scales of pain and other symptoms, as well as patient descriptors.</p><p>The analgesic effect of ketamine, lidocaine and morphine were assessed in a double blind, placebo-controlled, randomized study design. Three groups of patients were studied: patients with peripheral neuropathic pain of traumatic origin, patients with central post-stroke pain and patients with neuropathic pain after spinal cord injury. Somatosensory function was examined to see if this could predict response to treatment and to investigate if the drugs caused changes in thermal or mechanical sensibility.</p><p>The results shows that the intense pain, limited efficacy and tolerability of available treatments, the low overall rating of health, reduced work status and troublesome symptoms constitute a substantial impact on the quality of life for patients with peripheral neuropathic pain.</p><p>The NMDA-antagonist ketamine yielded substantial pain relief to patients with peripheral neuropathic pain and patients with neuropathic pain after spinal cord injury. However, the reported side effects limit the clinical usefulness of the treatment. Lidocaine did not give significant pain relief to the patients in the three studied groups. Morphine may represent a therapeutic alternative for some patients with central post-stroke pain, although only a small group of this category of patients responded with analgesia.</p><p>Assessment of baseline somatosensory functions could not be used to identify responders to treatment with either drug, nor did ketamine, lidocaine or morphine cause any changes in thermal or mechanical sensibility.</p>

<p>Septic shock is frequently seen in intensive care units and is associated with significant mortality. Endotoxin – a major mediator of the pathophysiologic responses – is released during lysis of Gram-negative bacteria. These responses can be mimicked in the endotoxaemic pig.</p><p>This thesis focuses on the following topics: the inflammatory and pathophysiological responses to various endotoxin doses and infusion patterns; covariations between endotoxin induced inflammatory and pathophysiological responses; whether the biological effects of endotoxin can be modulated by clopidogrel and whether tobramycin or ceftazidime reduce plasma cytokine levels.</p><p>Endotoxin induced linear log-log cytokine and F2-isoprostane responses. Leukocyte and platelet responses, pulmonary compliance, circulatory variables as well as indicators of plasma leakage and hypoperfusion exhibited log-linear responses to the endotoxin dose. Biological responses to endotoxaemia such as inflammation, hypotension, hypoperfusion and organ dysfunction were more expressed when the organism was exposed to endotoxin at a higher rate. These results may facilitate the possibility to choose relevant endotoxin administration, when experiments are set up in order to evaluate certain responses to endotoxaemia.</p><p>Correlation studies between cytokines, leukocytes, platelets and the endotoxin dose were in agreement with the well-known ability of endotoxin to induce cytokine expression and to activate both primary haemostasis and leukocytes. Free radical mediated lipid peroxidation and COX-mediated inflammation correlated to cytokine expression and organ dysfunction in endotoxaemic shock. </p><p>Endotoxaemic pigs pretreated with clopidogrel, exhibited a trend towards less expressed deterioration of renal function, although blocking of ADP-induced primary haemostasis is not a key mediator of endotoxin induced deterioration of renal function.</p><p>Tobramycin did not neutralise the biological effects of endotoxin or the plasma levels of endotoxin, suggesting that these antibiotics do not bind to endotoxin.</p><p>Reduction in IL-6 was greater in pigs treated with ceftazidime and tobramycin as compared with those given saline, indicating a possible anti-inflammatory effect of both antibiotics.</p>

Neuropathic pain of central and peripheral origin presents a substantial clinical problem as it is often resistant to pharmacological treatment. The health related quality of life of 126 patients with peripheral neuropathic pain was studied, to provide a cross sectional description from this point of view. Two generic health-related quality of life instruments; the SF-36 and the Nottingham Health Profile were used together with pain assessments, global rating of health and verbal rating scales of pain and other symptoms, as well as patient descriptors. The analgesic effect of ketamine, lidocaine and morphine were assessed in a double blind, placebo-controlled, randomized study design. Three groups of patients were studied: patients with peripheral neuropathic pain of traumatic origin, patients with central post-stroke pain and patients with neuropathic pain after spinal cord injury. Somatosensory function was examined to see if this could predict response to treatment and to investigate if the drugs caused changes in thermal or mechanical sensibility. The results shows that the intense pain, limited efficacy and tolerability of available treatments, the low overall rating of health, reduced work status and troublesome symptoms constitute a substantial impact on the quality of life for patients with peripheral neuropathic pain. The NMDA-antagonist ketamine yielded substantial pain relief to patients with peripheral neuropathic pain and patients with neuropathic pain after spinal cord injury. However, the reported side effects limit the clinical usefulness of the treatment. Lidocaine did not give significant pain relief to the patients in the three studied groups. Morphine may represent a therapeutic alternative for some patients with central post-stroke pain, although only a small group of this category of patients responded with analgesia. Assessment of baseline somatosensory functions could not be used to identify responders to treatment with either drug, nor did ketamine, lidocaine or morphine cause any changes in thermal or mechanical sensibility.

Septic shock is frequently seen in intensive care units and is associated with significant mortality. Endotoxin – a major mediator of the pathophysiologic responses – is released during lysis of Gram-negative bacteria. These responses can be mimicked in the endotoxaemic pig. This thesis focuses on the following topics: the inflammatory and pathophysiological responses to various endotoxin doses and infusion patterns; covariations between endotoxin induced inflammatory and pathophysiological responses; whether the biological effects of endotoxin can be modulated by clopidogrel and whether tobramycin or ceftazidime reduce plasma cytokine levels. Endotoxin induced linear log-log cytokine and F2-isoprostane responses. Leukocyte and platelet responses, pulmonary compliance, circulatory variables as well as indicators of plasma leakage and hypoperfusion exhibited log-linear responses to the endotoxin dose. Biological responses to endotoxaemia such as inflammation, hypotension, hypoperfusion and organ dysfunction were more expressed when the organism was exposed to endotoxin at a higher rate. These results may facilitate the possibility to choose relevant endotoxin administration, when experiments are set up in order to evaluate certain responses to endotoxaemia. Correlation studies between cytokines, leukocytes, platelets and the endotoxin dose were in agreement with the well-known ability of endotoxin to induce cytokine expression and to activate both primary haemostasis and leukocytes. Free radical mediated lipid peroxidation and COX-mediated inflammation correlated to cytokine expression and organ dysfunction in endotoxaemic shock. Endotoxaemic pigs pretreated with clopidogrel, exhibited a trend towards less expressed deterioration of renal function, although blocking of ADP-induced primary haemostasis is not a key mediator of endotoxin induced deterioration of renal function. Tobramycin did not neutralise the biological effects of endotoxin or the plasma levels of endotoxin, suggesting that these antibiotics do not bind to endotoxin. Reduction in IL-6 was greater in pigs treated with ceftazidime and tobramycin as compared with those given saline, indicating a possible anti-inflammatory effect of both antibiotics.

Ovariohysterectomy and castration are common surgical procedures in small animal practice that can result in clinically significant postoperative pain. One way of controlling postoperative pain is administration of a single analgesic or a combination of different classes of analgesics prior to the onset of noxious stimuli. A constraint to the perioperative use of traditional opioids and non-steroidal anti-inflammatory drugs (NSAIDs) is their undesirable side effects. In this series of experiments, the preventive (pre-emptive) analgesic efficacy of two popular human analgesics, tramadol (an ?atypical? opioid) and parecoxib (a NSAID with selective COX-2 inhibition) was evaluated in dogs. Initially, the efficacy and renal safety of parecoxib, tramadol and a combination of parecoxib, tramadol and pindolol (a -adrenoceptor blocker and 5-HT1A/1B antagonist) were screened in anaesthetised healthy dogs. These analgesics increased the dogs? nociceptive threshold to mechanical stimuli, without causing significant alterations in the dogs? glomerular filtration rate (GFR) estimated by plasma iohexol clearance. Subsequently, the efficacy of tramadol was compared with morphine, in dogs undergoing ovariohysterectomy or castration. The Glasgow composite measure pain scale-short form score (CMPS-SF) and changes in intraoperative electroencephalogram (EEG) responses were used to assess the efficacy of analgesics. Of the three treatment groups (preoperative morphine, 0.5 mg kg-1; preoperative tramadol, 3 mg kg-1; a ?combination? of preoperative low-dose morphine, 0.1 mg kg-1, and postoperative tramadol 3 mg kg-1), dogs given the ?combination? had significantly lower pain scores after ovariohysterectomy. In castrated dogs, preoperative tramadol (3 mg kg-1) and morphine (0.5 mg kg-1) were tested and no significant difference in the CMPS-SF score were observed between them. Changes in EEG variables were not specific between the treatment groups in ovariohysterectomised dogs. Finally, the efficacy of test drugs was evaluated against acute noxious electrical stimulation in anaesthetised dogs, using EEG. Median frequency of the EEG, a reliable indicator of nociception, increased significantly in tramadol and parecoxib groups, compared to morphine, after electrical stimulation. These studies demonstrated that tramadol and parecoxib can produce analgesia in dogs with insignificant side effects. The efficacy of tramadol appears to vary with the type of noxious stimulus. A complete prevention of noxious input by administration of analgesics pre- and post-operatively could have important clinical applications.

Ovariohysterectomy and castration are common surgical procedures in small animal practice that can result in clinically significant postoperative pain. One way of controlling postoperative pain is administration of a single analgesic or a combination of different classes of analgesics prior to the onset of noxious stimuli. A constraint to the perioperative use of traditional opioids and non-steroidal anti-inflammatory drugs (NSAIDs) is their undesirable side effects. In this series of experiments, the preventive (pre-emptive) analgesic efficacy of two popular human analgesics, tramadol (an ?atypical? opioid) and parecoxib (a NSAID with selective COX-2 inhibition) was evaluated in dogs. Initially, the efficacy and renal safety of parecoxib, tramadol and a combination of parecoxib, tramadol and pindolol (a -adrenoceptor blocker and 5-HT1A/1B antagonist) were screened in anaesthetised healthy dogs. These analgesics increased the dogs? nociceptive threshold to mechanical stimuli, without causing significant alterations in the dogs? glomerular filtration rate (GFR) estimated by plasma iohexol clearance. Subsequently, the efficacy of tramadol was compared with morphine, in dogs undergoing ovariohysterectomy or castration. The Glasgow composite measure pain scale-short form score (CMPS-SF) and changes in intraoperative electroencephalogram (EEG) responses were used to assess the efficacy of analgesics. Of the three treatment groups (preoperative morphine, 0.5 mg kg-1; preoperative tramadol, 3 mg kg-1; a ?combination? of preoperative low-dose morphine, 0.1 mg kg-1, and postoperative tramadol 3 mg kg-1), dogs given the ?combination? had significantly lower pain scores after ovariohysterectomy. In castrated dogs, preoperative tramadol (3 mg kg-1) and morphine (0.5 mg kg-1) were tested and no significant difference in the CMPS-SF score were observed between them. Changes in EEG variables were not specific between the treatment groups in ovariohysterectomised dogs. Finally, the efficacy of test drugs was evaluated against acute noxious electrical stimulation in anaesthetised dogs, using EEG. Median frequency of the EEG, a reliable indicator of nociception, increased significantly in tramadol and parecoxib groups, compared to morphine, after electrical stimulation. These studies demonstrated that tramadol and parecoxib can produce analgesia in dogs with insignificant side effects. The efficacy of tramadol appears to vary with the type of noxious stimulus. A complete prevention of noxious input by administration of analgesics pre- and post-operatively could have important clinical applications.

Ovariohysterectomy and castration are common surgical procedures in small animal practice that can result in clinically significant postoperative pain. One way of controlling postoperative pain is administration of a single analgesic or a combination of different classes of analgesics prior to the onset of noxious stimuli. A constraint to the perioperative use of traditional opioids and non-steroidal anti-inflammatory drugs (NSAIDs) is their undesirable side effects. In this series of experiments, the preventive (pre-emptive) analgesic efficacy of two popular human analgesics, tramadol (an ?atypical? opioid) and parecoxib (a NSAID with selective COX-2 inhibition) was evaluated in dogs. Initially, the efficacy and renal safety of parecoxib, tramadol and a combination of parecoxib, tramadol and pindolol (a -adrenoceptor blocker and 5-HT1A/1B antagonist) were screened in anaesthetised healthy dogs. These analgesics increased the dogs? nociceptive threshold to mechanical stimuli, without causing significant alterations in the dogs? glomerular filtration rate (GFR) estimated by plasma iohexol clearance. Subsequently, the efficacy of tramadol was compared with morphine, in dogs undergoing ovariohysterectomy or castration. The Glasgow composite measure pain scale-short form score (CMPS-SF) and changes in intraoperative electroencephalogram (EEG) responses were used to assess the efficacy of analgesics. Of the three treatment groups (preoperative morphine, 0.5 mg kg-1; preoperative tramadol, 3 mg kg-1; a ?combination? of preoperative low-dose morphine, 0.1 mg kg-1, and postoperative tramadol 3 mg kg-1), dogs given the ?combination? had significantly lower pain scores after ovariohysterectomy. In castrated dogs, preoperative tramadol (3 mg kg-1) and morphine (0.5 mg kg-1) were tested and no significant difference in the CMPS-SF score were observed between them. Changes in EEG variables were not specific between the treatment groups in ovariohysterectomised dogs. Finally, the efficacy of test drugs was evaluated against acute noxious electrical stimulation in anaesthetised dogs, using EEG. Median frequency of the EEG, a reliable indicator of nociception, increased significantly in tramadol and parecoxib groups, compared to morphine, after electrical stimulation. These studies demonstrated that tramadol and parecoxib can produce analgesia in dogs with insignificant side effects. The efficacy of tramadol appears to vary with the type of noxious stimulus. A complete prevention of noxious input by administration of analgesics pre- and post-operatively could have important clinical applications.

Ovariohysterectomy and castration are common surgical procedures in small animal practice that can result in clinically significant postoperative pain. One way of controlling postoperative pain is administration of a single analgesic or a combination of different classes of analgesics prior to the onset of noxious stimuli. A constraint to the perioperative use of traditional opioids and non-steroidal anti-inflammatory drugs (NSAIDs) is their undesirable side effects. In this series of experiments, the preventive (pre-emptive) analgesic efficacy of two popular human analgesics, tramadol (an ?atypical? opioid) and parecoxib (a NSAID with selective COX-2 inhibition) was evaluated in dogs. Initially, the efficacy and renal safety of parecoxib, tramadol and a combination of parecoxib, tramadol and pindolol (a -adrenoceptor blocker and 5-HT1A/1B antagonist) were screened in anaesthetised healthy dogs. These analgesics increased the dogs? nociceptive threshold to mechanical stimuli, without causing significant alterations in the dogs? glomerular filtration rate (GFR) estimated by plasma iohexol clearance. Subsequently, the efficacy of tramadol was compared with morphine, in dogs undergoing ovariohysterectomy or castration. The Glasgow composite measure pain scale-short form score (CMPS-SF) and changes in intraoperative electroencephalogram (EEG) responses were used to assess the efficacy of analgesics. Of the three treatment groups (preoperative morphine, 0.5 mg kg-1; preoperative tramadol, 3 mg kg-1; a ?combination? of preoperative low-dose morphine, 0.1 mg kg-1, and postoperative tramadol 3 mg kg-1), dogs given the ?combination? had significantly lower pain scores after ovariohysterectomy. In castrated dogs, preoperative tramadol (3 mg kg-1) and morphine (0.5 mg kg-1) were tested and no significant difference in the CMPS-SF score were observed between them. Changes in EEG variables were not specific between the treatment groups in ovariohysterectomised dogs. Finally, the efficacy of test drugs was evaluated against acute noxious electrical stimulation in anaesthetised dogs, using EEG. Median frequency of the EEG, a reliable indicator of nociception, increased significantly in tramadol and parecoxib groups, compared to morphine, after electrical stimulation. These studies demonstrated that tramadol and parecoxib can produce analgesia in dogs with insignificant side effects. The efficacy of tramadol appears to vary with the type of noxious stimulus. A complete prevention of noxious input by administration of analgesics pre- and post-operatively could have important clinical applications.

Ovariohysterectomy and castration are common surgical procedures in small animal practice that can result in clinically significant postoperative pain. One way of controlling postoperative pain is administration of a single analgesic or a combination of different classes of analgesics prior to the onset of noxious stimuli. A constraint to the perioperative use of traditional opioids and non-steroidal anti-inflammatory drugs (NSAIDs) is their undesirable side effects. In this series of experiments, the preventive (pre-emptive) analgesic efficacy of two popular human analgesics, tramadol (an ?atypical? opioid) and parecoxib (a NSAID with selective COX-2 inhibition) was evaluated in dogs. Initially, the efficacy and renal safety of parecoxib, tramadol and a combination of parecoxib, tramadol and pindolol (a -adrenoceptor blocker and 5-HT1A/1B antagonist) were screened in anaesthetised healthy dogs. These analgesics increased the dogs? nociceptive threshold to mechanical stimuli, without causing significant alterations in the dogs? glomerular filtration rate (GFR) estimated by plasma iohexol clearance. Subsequently, the efficacy of tramadol was compared with morphine, in dogs undergoing ovariohysterectomy or castration. The Glasgow composite measure pain scale-short form score (CMPS-SF) and changes in intraoperative electroencephalogram (EEG) responses were used to assess the efficacy of analgesics. Of the three treatment groups (preoperative morphine, 0.5 mg kg-1; preoperative tramadol, 3 mg kg-1; a ?combination? of preoperative low-dose morphine, 0.1 mg kg-1, and postoperative tramadol 3 mg kg-1), dogs given the ?combination? had significantly lower pain scores after ovariohysterectomy. In castrated dogs, preoperative tramadol (3 mg kg-1) and morphine (0.5 mg kg-1) were tested and no significant difference in the CMPS-SF score were observed between them. Changes in EEG variables were not specific between the treatment groups in ovariohysterectomised dogs. Finally, the efficacy of test drugs was evaluated against acute noxious electrical stimulation in anaesthetised dogs, using EEG. Median frequency of the EEG, a reliable indicator of nociception, increased significantly in tramadol and parecoxib groups, compared to morphine, after electrical stimulation. These studies demonstrated that tramadol and parecoxib can produce analgesia in dogs with insignificant side effects. The efficacy of tramadol appears to vary with the type of noxious stimulus. A complete prevention of noxious input by administration of analgesics pre- and post-operatively could have important clinical applications.