Tamara L. Grubb

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.

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.

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.

Pulsed delivery of inhaled nitric oxide counteracts hypoxaemia during 2.5 hours of inhalation anaesthesia in dorsally recumbent horses.

OBJECTIVE The study aimed to investigate the effect of varying pulse lengths of inhaled nitric oxide (iNO), and 2.5 hours of continuous pulse-delivered iNO on pulmonary gas exchange in anaesthetized horses. STUDY DESIGN Experimental study. ANIMALS Six Standardbred horses. METHODS Horses received acepromazine, detomidine, guaifenesin, thiopentone and isoflurane in oxygen, were positioned in dorsal recumbency and were breathing spontaneously. iNO was on average pulsed during the first 20, 30, 43 or 73% of the inspiration in 15 minute steps. The pulse length that corresponded to the highest (peak) partial pressure of arterial oxygen (PaO(2) ) in the individual horses was determined and delivered for a further 1.5 hours. Data measured or calculated included arterial and mixed venous partial pressures of O(2) and CO(2) , heart rate, respiratory rate, expired minute ventilation, pulmonary and systemic arterial mean pressures, cardiac output and venous admixture. Data (mean ± SD) was analysed using anova with p < 0.05 considered significant. RESULTS Although the pulse length of iNO that corresponded to peak PaO(2) varied between horses, administration of all pulse lengths of iNO increased PaO(2) compared to baseline. The shortest pulse lengths that resulted in the peak PaO(2) were 30 and 43% of the inspiration. Administration of iNO increased PaO(2) (12.6 ± 4.1 kPa [95 ± 31 mmHg] at baseline to a range of 23.0 ± 8.4 to 25.3 ± 9.0 kPa [173 to 190 mmHg]) and PaCO(2) (8.5 ± 1.2 kPa [64 ± 9 mmHg] to 9.8 ± 1.5 kPa [73 ± 11 mmHg]) and decreased venous admixture from 32 ± 6% to 25 ± 6%. The increase in PaO(2) and decrease in venous admixture was sustained for the entire 2.5 hours of iNO delivery. CONCLUSIONS The improvement in arterial oxygenation during pulsed delivery of iNO was significant and sustained throughout 2.5 hours of anaesthesia. CLINICAL RELEVANCE Pulsed iNO potentially could be used clinically to counteract hypoxemia in anaesthetized horses.

What Do We Really Know About the Drugs We Use to Treat Chronic Pain

Chronic pain can be extremely hard to treat in both humans and animals, and effective pain relief often requires the use of novel analgesic drugs. Little true scientific data actually exist for some of the drugs that we use to alleviate chronic pain, yet dosing protocols and expected results are available. The scientific data (pharmacokinetic/pharmacodynamic data) available for drugs used to treat chronic pain in veterinary patients will be presented along with published dosages and dosing guidelines.

Anesthesia for Patients with Respiratory Disease and/or Airway Compromise

Because the airway extends from the oral or nasal cavity to the alveoli, airway compromise or respiratory disease has numerous manifestations. Complications can be encountered in both the upper and lower airways and include a vast range of problems including laryngeal paralysis, collapsing trachea, pneumonia, pulmonary edema, pneumothorax, intrathoracic masses and diaphragmatic hernias. Anesthesia can cause further complications because anesthetic drugs and equipment can exacerbate or even cause airway difficulties and respiratory compromise. When anesthetizing patients with respiratory disease or airway complications, the choice of the actual anesthetic drugs is not necessarily dictated by the presence of respiratory compromise, but rather by the overall health of the patient. The choice of anesthetic technique (e.g., method of induction, method of intubation, use of positive-pressure ventilation, etc.), on the other hand, is often critical.

Physiologic responses and plasma endothelin-1 concentrations associated with abrupt cessation of nitric oxide inhalation in isoflurane-anesthetized horses

OBJECTIVE To assess physiologic responses and plasma endothelin (ET)-1 concentrations associated with abrupt cessation of nitric oxide (NO) inhalation in isoflurane-anesthetized horses. ANIMALS 6 healthy adult Standardbreds. PROCEDURES Horses were anesthetized with isoflurane in oxygen and placed in dorsal recumbency. Nitric oxide was pulsed into the respiratory tract for 2.5 hours, and then administration was abruptly discontinued. Just prior to commencement and at cessation of NO administration, and at intervals during a 30-minute period following cessation of NO inhalation, several variables including PaO(2), mean pulmonary artery pressure, venous admixture or pulmonary shunt fraction (Qs/Qt), and plasma ET-1 concentration were recorded or calculated. RESULTS After cessation of NO inhalation, PaO(2) decreased slowly but significantly (172.7 +/- 29.8 mm Hg to 84.6 +/- 10.9 mm Hg) and Qs/Qt increased slowly but significantly (25 +/- 2% to 40 +/- 3%) over a 30-minute period. Mean pulmonary artery pressure increased slightly (14.0 +/- 1.3 mm Hg to 16.8 +/- 1 mm Hg) over the same time period. No change in serum ET-1 concentration was detected, and other variables did not change or underwent minor changes. CONCLUSIONS AND CLINICAL RELEVANCE The improvement in arterial oxygenation during pulsed inhalation of NO to healthy isoflurane-anesthetized horses decreased only gradually during a 30-minute period following cessation of NO inhalation, and serum ET-1 concentration was not affected. Because a rapid rebound response did not develop, inhalation of NO might be clinically useful in the treatment of hypoxemia in healthy isoflurane-anesthetized horses.

The effects of pulse-delivered inhaled nitric oxide on arterial oxygenation, ventilation-perfusion distribution and plasma endothelin-1 concentration in laterally recumbent isoflurane-anaesthetized horses

OBJECTIVES Anaesthetized horses commonly become hypoxaemic due to ventilation/perfusion (V·A/Q·) mismatch and increased pulmonary shunt fraction (Qs·/Qt·). Pulse-delivered inhaled nitric oxide may improve oxygenation but may increase plasma concentration of the potent vasoconstrictor, endothelin-1 (ET-1). Objectives: Study 1) compare arterial oxygen concentration (PaO2) and saturation (SaO2), calculated Qs·/Qt· and ET-1 concentration; and Study 2) assess V·A/Q· matching and measured Qs·/Qt· in isoflurane-anaesthetized horses in left lateral recumbency receiving pulse-delivered inhaled nitric oxide (PiNO group) or inhalant gas only (C group). STUDY DESIGN Prospective research trial. ANIMALS Ten Healthy adult Standardbred horses. Two horses were anaesthestized in both groups in a random cross-over design with >4 weeks between studies. METHODS Study 1) Cardiopulmonary data including PaO2, SaO2, Qs·/Qt· and ET-1 concentration were measured or calculated prior to and at various points during PiNO administration in 6PiNO and 6C horses. Two-way repeated measures anova with Bonferroni significant difference test was used for data analysis with p < 0.05 considered significant. Study 2) V·A/Q· matching and Qs·/Qt· were determined using the multiple inert gas elimination technique in 3 horses. Data were collected after 60 minutes of anaesthesia without PiNO (baseline) and 15 minutes after PiNO was pulsed during the first 30%, and then the first 60%, of inspiration. Data were descriptive only. RESULTS Study 1) PaO2 and SaO2 were higher and calculated Qs·/Qt· was lower in the PiNO group than the C group at most time points. ET-1 was not different over time or between groups. Study 2) V·A/Q· matching and measured Qs·/Qt· were improved from baseline in all horses but PiNO60% provided no improvement when compared to PiNO30%. CONCLUSIONS AND CLINICAL RELEVANCE PiNO delivered in the initial portion of the inspiration effectively relieves hypoxaemia in anaesthetized horses by improving V·A/Q· matching and decreasing Qs·/Qt· without affecting ET-1.

Oxygenation and plasma endothelin‐1 concentrations in healthy horses recovering from isoflurane anaesthesia administered with or without pulse‐delivered inhaled nitric oxide

OBJECTIVE To assess oxygenation, ventilation-perfusion (V/Q) matching and plasma endothelin (ET-1) concentrations in healthy horses recovering from isoflurane anaesthesia administered with or without pulse-delivered inhaled nitric oxide (iNO). STUDY DESIGN Prospective experimental trial. ANIMALS Healthy adult Standardbred horses. METHODS Horses were anaesthetized with isoflurane in oxygen and placed in lateral recumbency. Six control (C group) horses were anaesthetized without iNO delivery and six horses received pulse-delivered iNO (NO group). After 2.5 hours of anaesthesia isoflurane and iNO were abruptly discontinued, inhaled oxygen was reduced from 100% to approximately 30%, and the horses were moved to the recovery stall. At intervals during a 30-minute period following the discontinuation of anaesthesia, arterial and mixed venous blood gas values, shunt fraction (Qs/Qt), plasma ET-1 concentration, pulse rate and respiratory rate were measured or calculated. Repeated measures anova and a Bonferroni post hoc test was used to analyze data with significance set at p < 0.05. RESULTS At all time points in the recovery period, NO horses maintained better arterial oxygenation (oxygen partial pressure: NO 13.2 ± 2.7-11.1 ± 2.7 versus C 6.7 ± 1.1-7.1 ± 1.1 kPa) and better V/Q matching (Qs/Qt NO 0.23 ± 0.05-0.14 ± 0.06 versus C 0.48 ± 0.03-0.32 ± 0.08%) than C horses. Mixed venous oxygenation was higher in NO for 25 minutes following the discontinuation of anaesthesia (NO 6.3 ± 0.2-4.5 ± 0.07 versus C 4.7 ± 0.6-3.7 ± 0.3 kPa). In both groups of horses arterial oxygenation remained fairly stable; venous oxygenation declined over this time period in the NO group but still remained higher than venous oxygen in the C group. ET-1 concentrations were higher at most time points in C than NO. Changes in other parameters were either minor or absent. CONCLUSIONS AND CLINICAL RELEVANCE Delivery of iNO to healthy horses during anaesthesia results in better arterial and venous oxygenation and V/Q matching (as determined by lower Qs/Qt) and lower ET-1 concentrations throughout a 30-minute anaesthetic recovery period.