Stephen A. Greene

Effects of 6% hetastarch (600/0.75) or lactated Ringer’s solution on hemostatic variables and clinical bleeding in healthy dogs anesthetized for orthopedic surgery

OBJECTIVE To evaluate and compare hemostatic variables and clinical bleeding following the administration of 6% hetastarch (600/0.75) or lactated Ringers solution (LRS) to dogs anesthetized for orthopedic surgery. STUDY DESIGN Randomized blinded prospective study. ANIMALS Fourteen, healthy adult mixed-breed hound dogs of either sex, aged 11-13 months, and weighing 20.8±1.2 kg. METHODS The dogs were randomly assigned to receive a 10 mL kg(-1) intravenous (i.v.) bolus of either 6% hetastarch (600/0.75) or LRS over 20 minutes followed by a maintenance infusion of LRS (10 mL kg(-1)  hour(-1)) during anesthesia. Before (Baseline) and at 1 and 24 hours after bolus administration, packed cell volume (PCV), total protein concentration (TP), prothrombin time (PT), activated partial thromboplastin time (APTT), von Willebrands factor antigen concentration (vWF:Ag), factor VIII coagulant activity (F VIII:C), platelet count, platelet aggregation, colloid osmotic pressure (COP) and buccal mucosal bleeding time (BMBT) were measured. In addition a surgeon who was blinded to the treatments assessed bleeding from the incision site during the procedure and at 1 and 24 hours after the bolus administration. RESULTS Following hetastarch or LRS administration, the PCV and TP decreased significantly 1-hour post-infusion. APTT did not change significantly compared to baseline in either treatment group, but the PT was significantly longer at 1-hour post-infusion than at 24 hours in both groups. No significant change was detected for vWF:Ag, FVIII:C, platelet aggregation or clinical bleeding in either group. The BMBT increased while platelet count decreased significantly at 1-hour post-infusion in both groups. The COP decreased significantly in both treatment groups 1-hour post-infusion but was significantly higher 1-hour post-infusion in the hetastarch group compared to the LRS group. CONCLUSIONS AND CLINICAL RELEVANCE At the doses administered, both hetastarch and LRS can alter hemostatic variables in healthy dogs. However, in these dogs undergoing orthopedic surgery, neither fluid was associated with increased clinical bleeding.

P-glycoprotein contributes to the blood-brain, but not blood-cerebrospinal fluid, barrier in a spontaneous canine p-glycoprotein knockout model.

P-glycoprotein is considered to be a major factor impeding effective drug therapy for many diseases of the central nervous system (CNS). Thus, efforts are being made to gain a better understanding of P-glycoproteins role in drug distribution to brain parenchyma and cerebrospinal fluid (CSF). The goal of this study was to validate and introduce a novel P-glycoprotein–deficient (ABCB1-1Δ) canine model for studying P-glycoprotein–mediated effects of drug distribution to brain tissue and CSF. CSF concentrations of drug are often used to correlate efficacy of CNS drug therapy as a surrogate for determining drug concentration in brain tissue. A secondary goal of this study was to investigate the validity of using CSF concentrations of P-glycoprotein substrates to predict brain tissue concentrations. Loperamide, an opioid that is excluded from the brain by P-glycoprotein, was used to confirm a P-glycoprotein–null phenotype in the dog model. ABCB1-1Δ dogs experienced CNS depression following loperamide administration, whereas ABCB1 wild-type dogs experienced no CNS depression. In summary, we have validated a novel P-glycoprotein–deficient canine model and have used the model to investigate transport of the P-glycoprotein substrate 99mTc-sestamibi at the blood-brain barrier and blood-CSF barrier.

Cardiovascular and respiratory effects, and quality of anesthesia produced by alfaxalone administered intramuscularly to cats sedated with dexmedetomidine and hydromorphone

The cardiovascular and respiratory effects, and the quality of anesthesia of alfaxalone administered intramuscularly (IM) to cats sedated with dexmedetomidine and hydromorphone were evaluated. Twelve healthy adult cats were anesthetized, with six cats receiving dexmedetomidine (0.01 mg/kg IM) followed by alfaxalone (5 mg/kg IM; group DA) and six receiving dexmedetomidine (0.01 mg/kg IM) plus hydromorphone (0.1 mg/kg IM) followed by alfaxalone (5 mg/kg IM; group DHA). Cardiorespiratory (pulse rate, blood pressure, respiratory rate, saturation of oxygen with hemoglobin, end tidal carbon dioxide partial pressure) and bispectral index (BIS) data were collected every 10 mins for 90 mins starting immediately after intubation. The quality of anesthesia was scored by a blinded researcher at induction and at 5 and 60 mins after extubation. Recovery scores ranged from 1 (prolonged struggling) to 4 (no struggling). There were no clinically significant (P >0.05) differences in any data between groups or over time. Physiologic parameters were within normal limits for cats at all times. BIS values were consistent with light anesthesia in both groups. However, recovery was prolonged and marked with excitement, ataxia and hyper-reactivity in all cats. Thus, although cardiovascular and respiratory parameters are stable following IM injection of alfaxalone to cats sedated with dexmedetomidine and hydromorphone, recovery is extremely poor and this route of administration is not recommended for anesthesia in cats.

Protocols for anesthesia of cattle

The article explores the choices and considerations pertinent to the selection of an anesthetic protocol for use in cattle. When the veterinarian is presented with the opportunity to provide anesthesia for surgical or diagnostic procedures, the options include use of local anesthetics, sedative-tranquilizer and analgesic combinations, or general anesthetic techniques. Informed decisions regarding selection of an anesthetic technique or protocol are made possible with understanding of the perianesthetic considerations commonly recognized for cattle.

Pros and cons of using α-2 agonists in small animal anesthesia practice

The α-2 agonists have been used in veterinary practice for over 30 years following the introduction of xylazine (ROMPUN, Bayer Corp., Shawnee Mission, KS) in 1962. The decision to use α-2 agonists in anesthesia practice should be based on factors including patient disposition, presenting complaint, type of procedure, and the veterinarians familiarity with the drug. Controversy surrounds the issue of using anticholinergic agents concurrent with the α-2 agonists. Patient selection and procedure type can aid in determining when use of an anticholinergic with the α-2 agonist is advantageous. Antagonism of α-2 agonists can be readily accomplished. Commonly, α-2 agonists are used in combination with other agents to provide neuroleptanalgesia or sedation prior to general anesthesia.

Effects of intratesticular injection of bupivacaine and epidural administration of morphine in dogs undergoing castration

OBJECTIVE To determine the intraoperative and postoperative analgesic efficacy of intratesticular or epidural injection of analgesics for dogs undergoing castration. DESIGN Randomized controlled trial. ANIMALS 51 healthy male dogs. PROCEDURES Dogs were assigned to a control group that received analgesics systemically (hydromorphone [0.1 mg/kg {0.045 mg/lb}, IM] and carprofen [4.4 mg/kg {2.0 mg/lb}, SC]; n = 17), an epidural treatment group that received analgesics systemically and morphine (0.1 mg/kg) epidurally (17), or an intratesticular treatment group that received analgesics systemically and bupivacaine (0.5 mg/kg [0.23 mg/lb]/testis) intratesticularly (17). Dogs were anesthetized and castrated by veterinary students. Responses to surgical stimulation were monitored intraoperatively, and treatments were administered as required. Pain scores were assigned via a modified Glasgow composite pain scale after surgery. Serum cortisol concentrations were determined at various times. Rescue analgesia included fentanyl (intraoperatively) and hydromorphone (postoperatively). RESULTS Compared with control dogs, dogs in the intratesticular bupivacaine and epidural morphine treatment groups received significantly fewer doses of fentanyl intraoperatively (11, 1, and 5 doses, respectively) and hydromorphone postoperatively (14, 7, and 3 doses, respectively) and had significantly lower postoperative pain scores (mean ± SEM score at first assessment time, 71 ± 0.5, 4.8 ± 0.2, and 4.5 ± 0.4, respectively). At 15 minutes after removal of the testes, serum cortisol concentrations were significantly higher than they were immediately prior to surgery for all groups and values for the intratesticular bupivacaine treatment group were significantly lower versus the other 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE Intratesticular or epidural injection of analgesics improved perioperative analgesia for dogs undergoing castration.

Tramadol metabolism to O-desmethyl tramadol (M1) and N-desmethyl tramadol (M2) by dog liver microsomes: Species comparison and identification of responsible canine cytochrome P-450s (CYPs)

Tramadol is widely used to manage mild to moderately painful conditions in dogs. However, this use is controversial, since clinical efficacy studies in dogs showed conflicting results, whereas pharmacokinetic studies demonstrated relatively low circulating concentrations of O-desmethyltramadol (M1). Analgesia has been attributed to the opioid effects of M1, whereas tramadol and the other major metabolite (N-desmethyltramadol, M2) are considered inactive at opioid receptors. This study aimed to determine whether cytochrome P450 (P450)–dependent M1 formation by dog liver microsomes is slower compared with cat and human liver microsomes and to identify the P450s responsible for M1 and M2 formation in canine liver. Since tramadol is used as a racemic mixture of (+)- and (−)-stereoisomers, both (+)-tramadol and (−)-tramadol were evaluated as substrates. M1 formation from tramadol by liver microsomes from dogs was slower than from cats (3.9-fold) but faster than humans (7-fold). However, M2 formation by liver microsomes from dogs was faster than those from cats (4.8-fold) and humans (19-fold). Recombinant canine P450 activities indicated that M1 was formed by CYP2D15, whereas M2 was largely formed by CYP2B11 and CYP3A12. This was confirmed by dog liver microsome studies that showed selective inhibition of M1 formation by quinidine and M2 formation by chloramphenicol and CYP2B11 antiserum, as well as induction of M2 formation by phenobarbital. Findings were similar for both (+)-tramadol and (−)-tramadol. In conclusion, low circulating M1 concentrations in dogs are explained in part by low M1 formation and high M2 formation, which is mediated by CYP2D15 and CYP2B11/CYP3A12, respectively.

Cardiovascular effects of sevoflurane in Holstein calves

OBJECTIVE The purpose of this study was to determine the cardiovascular effects of sevoflurane in calves. STUDY DESIGN Prospective experimental study. ANIMALS Six, healthy, 8-12-week-old Holstein calves weighing 80 ± 4.5 (mean ± SEM) kg were studied. METHODS Anesthesia was induced by face-mask administration of 7% sevoflurane in O2. Calves tracheae were intubated, placed in right lateral recumbency, and maintained with 3.7% end-tidal concentration sevoflurane for 30 minutes to allow catheterization of the auricular artery and placement of a Swan-Ganz thermodilution catheter into the pulmonary artery. After instrumentation, administration of sevoflurane was temporarily discontinued until mean arterial pressure was > 100 mm Hg. Baseline values were recorded and the vaporizer output increased to administer 3.7% end-tidal sevoflurane concentration. Ventilation was controlled to maintain normocapnia. The following were recorded at 5, 10, 15, 30 and 45 minutes after collection of baseline data and expressed as the mean value (± SEM): direct systolic, diastolic, and mean arterial blood pressures; cardiac output; mean pulmonary arterial pressure; pulmonary arterial occlusion pressure, heart rate; and pulmonary arterial temperature. Cardiac index and systemic and pulmonary vascular resistance values were calculated using standard formulae. Arterial blood gases were analyzed at baseline, and at 15 and 45 minutes. Differences from baseline values were determined using one-way analysis of variance for repeated measures with post-hoc differences between mean values identified using Dunnets test (p < 0.05). RESULTS Mean time from beginning sevoflurane administration to intubation of the trachea was 224 ± 9 seconds. The mean end-tidal sevoflurane concentration at baseline was 0.7 (± 0.11)%. Sevoflurane anesthesia was associated with decreased arterial blood pressure at all sampling times. Mean arterial blood pressure decreased from a baseline value of 112 ± 7 mm Hg to a minimum value of 88 ± 4 mm Hg at 5 minutes. Compared with baseline, arterial pH was decreased at 15 minutes. Pulmonary arterial blood temperature was decreased at 15, 30 and 45 minutes. Arterial CO2 tension increased from a baseline value of 43 ± 3 to 54 ± 4 mm Hg (5.7 ± 0.4 to 7.2 ± 0.3 kPa) at 15 minutes. Mean pulmonary arterial pressure was increased at 30 and 45 minutes. Pulmonary arterial occlusion pressure increased from a baseline value of 18 ± 2 to 23 ± 2 mm Hg at 45 minutes. There were no significant changes in other measured variables. All calves recovered from anesthesia uneventfully. CONCLUSION We conclude that sevoflurane for induction and maintenance of anesthesia was effective and reliable in these calves and that neither hypotension nor decreased cardiac output was a clinical concern. CLINICAL RELEVANCE Use of sevoflurane for mask induction and maintenance of anesthesia in young calves is a suitable alternative to injectable and other inhalant anesthetics.

Chronic Pain: Pathophysiology and Treatment Implications

An examination of the current understanding of the processes and related therapies aimed at treatment of chronic pain in animals is presented. Discussion focuses on mechanisms involved in the neural pathways of chronic pain, differences between acute and chronic pain, and pharmacologic options for chronic pain as they relate to inflammatory, neoplastic, and neuropathic processes.

Anesthesia for Patients with Neurologic Disease

Cerebral blood flow may be altered in anesthetized patients, and this could be detrimental to patients with intracranial disease. Cerebral blood flow is autoregulated and held constant over a mean arterial pressure range of 50 to 150 mm Hg. Changes in cerebral blood volume are reflected by cerebral blood flow, whereas intracranial pressure varies directly with cerebral blood volume. Cerebral blood flow is also under chemical regulation and varies directly with arterial carbon dioxide tension over the range of 25 to 70 mm Hg. A reduction in arterial oxygen tension to below 60 mm Hg also dramatically increases cerebral blood flow. Changes in both arterial carbon dioxide and oxygen tensions are common in anesthetized patients. Furthermore, anesthetic drugs can alter cerebral blood flow. Injectable anesthetics, except ketamine, tend to preserve cerebral blood flow. Inhalant anesthetics may be associated with cerebral vasodilation, increased cerebral blood flow, and raised intracranial pressure. However, low concentrations of inhalant anesthetics combined with controlled ventilation are effective in preventing exacerbation of raised intracranial pressure. Factors affecting cerebral blood flow should be considered before anesthetizing patients with intracranial disease.