Comparison of preoperative retrobulbar bupivacaine and postoperative subcutaneous liposome-encapsulated bupivacaine on postoperative analgesia in dogs undergoing enucleation.

OBJECTIVE: To compare the effectiveness of preoperative bupivacaine inferotemporal retrobulbar blocks to postoperative liposome-encapsulated bupivacaine (Nocita) line blocks for analgesia following enucleation. ANIMALS: 39 client-owned dogs (40 eyes) presenting to the Ophthalmology Service for enucleation. METHODS: Dogs were randomly assigned to receive either a preoperative inferotemporal retrobulbar block with 0.5% bupivacaine or a peri-incisional line block with liposome-encapsulated bupivacaine (Nocita) at closure. Patients underwent unilateral enucleation and were hospitalized for 24 hours after surgery. Pain scores were performed by a masked observer with the Glasgow Composite Measure Pain Scale and the University of Wisconsin Ocular Pain Scale at 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours following surgery. Intraoperative use of blood pressure and anesthetic support mediations as well as need for rescue pain control were recorded and compared between groups. RESULTS: There was no significant difference in rescue rates between treatment groups. When comparing the use of medical intraoperative heart rate, blood pressure, or anesthetic plane support, there were no significant differences in use between groups. CLINICAL RELEVANCE: Use of preoperative bupivacaine retrobulbar blocks and postoperative Nocita line blocks were equally effective at postoperative pain control with similarly low complication rates.

The Effectiveness of Liposome-Encapsulated Bupivacaine Compared to Standard Bupivacaine for Anesthesia of the Maxilla in Dogs.

Medical and surgical procedures involving the canine maxilla can be painful both during and for several hours post-procedure. The length of this pain may exceed the predicted duration of standard bupivacaine or lidocaine. The goal of this study was to determine the duration and efficacy of sensory blockade of the maxilla produced by liposome-encapsulated bupivacaine (LB), compared to standard bupivacaine (B) or saline (0.9% NaCl) (S), when administered as a modified maxillary nerve block in dogs. Eight maxillae were studied bilaterally from 4 healthy dogs of the same breed and similar age. This prospective, randomized, crossover, blinded study evaluated a modified maxillary nerve block using 1.3% LB at 0.1 mL/kg, 0.5% B, or S at an equivalent volume. An electronic von Frey aesthesiometer (VFA) was used to evaluate mechanical nociceptive thresholds at 4 locations on each hemimaxilla at baseline and at specific intervals up to 72-h post-treatment. Both B and LB treatments resulted in significantly higher VFA thresholds when compared to S. Dogs that received B had VFA thresholds significantly higher than S for 5 to 6 h. Dogs that received LB had thresholds significantly higher than S for 6 to 12 h depending on the site of measurement. No complications were observed. Maxillary nerve block with B provided up to 6 h, and LB 12 h, of sensory blockade depending on the site tested.

Retrobulbar lidocaine injection via the supraorbital fossa is safe in adult horses but produces regionally variable periocular anaesthesia.

BACKGROUND: Injection techniques for retrobulbar anaesthesia are published in horses, but neither safety nor anaesthetic efficacy and duration have been evaluated objectively in vivo. OBJECTIVE: To characterise the safety and efficacy of one published technique for retrobulbar anaesthesia. STUDY DESIGN: Randomised, controlled descriptive experiment. METHODS: Unilateral retrobulbar injection with 10 mL lidocaine (2%) was performed in eight sedated adult mares. Contralateral eyes served as untreated controls. Neurophthalmic parameters, intraocular pressure (IOP), and corneal and periocular sensation were measured awake, post-sedation and at periodic time points for 24 hours following injection. Adverse effects were documented. RESULTS: Injection of 10 mL lidocaine significantly increased IOP for up to 2 hours (P < .05) maximally at 30 min (mean [95% CI]: 6.0 [2.7, 9.2] mm Hg, P < .001). Six of the eight treated eyes developed mild to moderate reversible chemosis for 2 to 24 hours. One eye developed severe chemosis and superficial corneal ulceration at 24 and 48 hours following injection respectively. Corneal sensitivity significantly decreased for 6 hours (P < .05), maximally at 10 min (-44.4 [-34.6, -54.1] mm, P < .001). Periocular sensitivity (measured as increase in applied force) significantly decreased dorsally and medially for up to 2 hours (maximal at 2 hours (367.1 [238.5, 495.7] g, P < .001, and at 30 min: 345.8 [202.6, 488.9] g, P < .001) respectively). Ventral and lateral sensitivity were not effectively decreased beyond 30 min. Optic nerve function was not consistently reduced following injection. MAIN LIMITATIONS: Investigators were not masked to the treated eye. CONCLUSIONS: Retrobulbar injection using 10 mL lidocaine is safe in normal eyes of adult horses, but carries risk in structurally compromised or glaucomatous eyes due to transient IOP increase. Reversible chemosis commonly develops 2-4h following injection, and may be severe in some horses with risk for corneal ulceration. Corneal anaesthesia is rapid and prolonged, but all periocular regions are not consistently anaesthetised. Retrobulbar injection should be combined with other local anaesthetic injections for eyelid surgeries or enucleations.

Retrospective analysis of complications associated with retrobulbar bupivacaine in dogs undergoing enucleation surgery.

OBJECTIVE: To investigate complications associated with, and without, bupivacaine retrobulbar local anesthesia in dogs undergoing unilateral enucleation surgery. STUDY DESIGN: Retrospective, observational study. ANIMALS: A total of 167 dogs underwent unilateral enucleation surgery via a transpalpebral approach. METHODS: Records from 167 dogs that underwent unilateral enucleation surgery that did (RB) or did not (NB) include retrobulbar bupivacaine anesthesia were reviewed, including anesthetic record, daily physical examination records, surgery report, patient discharge report and patient notes within 14 days of the surgery. Specific complications and severity were compared between RB and NB using the Wilcoxon rank-sum test. A 'complication burden' (0-5) comprising five prespecified complications was assigned and tested using rank-sum procedures. Statistical significance was set to 0.05. RESULTS: Group RB included 97 dogs and group NB 70 dogs. Dogs in NB had a 17.0 percentage points (points) greater risk for a postoperative recovery complication (38.6% versus 21.6%; 95% confidence interval: 3.0-30.6 points; p = 0.017). There was inconclusive evidence that dogs in group RB had a lower risk of requiring perioperative anticholinergic administration (12.4% versus 22.9%; 10.5 points; p = 0.073). Other complications were similar between groups RB and NB with risks that differed by <10 points. The risk of hemorrhage was similar between groups RB (22.7%) and NB (20.0%) with no significant difference in the level of severity (p = 0.664). CONCLUSIONS AND CLINICAL RELEVANCE: In this retrospective study, the use of retrobulbar bupivacaine for enucleation surgery in dogs was not associated with an increased risk of major or minor complications.

Effects of hetastarch 130/0.4 on plasma osmolality, colloid osmotic pressure and total protein in horses anaesthetised for elective surgical procedures.

Effects of lactated Ringer's solution (LRS) and hetastarch 130/0.4 (HES) on colloid osmotic pressure (COP), plasma osmolality (OSM) and total protein (TP) were investigated in 18 inhalational-anaesthetised healthy horses. Horses received 4-6 ml/kg LRS (LRS; n=9) or HES (HES; n=9) from anaesthesia induction through 60 min, after which all were administered LRS. COP, TP and OSM were measured before premedication (baseline), postinduction and 30 (n=18), 60 (n=18), 90 (n=18) and 120 (n=12) minutes. Baseline COP, OSM and TP were not different between groups. TP decreased in both groups at all time points after induction. OSM increased from baseline in HES at 30, 60, 90 and 120 minutes. COP decreased at 30-120 minutes in LRS, and at 90 and 120 minutes in HES. Mean COP was higher in HES than LRS at 30 (18.8±0.5 vs 16.3±0.4 mmHg (P=0.001)), 60 (19.1±0.5 vs 15.9±0.4 mmHg (P<0.0001)) and 90 (17.4±0.5 vs 15.4±0.5 mmHg (P=0.005)) minutes. Sixty minutes of HES infusion increases OSM and transiently maintains COP compared with an equal volume of LRS in anaesthetised horses.

Comparison of the effects of alfaxalone and propofol with acepromazine, butorphanol and/or doxapram on laryngeal motion and quality of examination in dogs.

OBJECTIVE: To compare the effects of alfaxalone and propofol, with and without acepromazine and butorphanol followed by doxapram, on laryngeal motion and quality of laryngeal examination in dogs. STUDY DESIGN: Randomized, crossover, blinded study. ANIMALS: Ten female Beagle dogs, aged 11-13 months and weighing 7.2-8.6 kg. METHODS: The dogs were administered four intravenous (IV) treatments: alfaxalone (ALF), alfaxalone+acepromazine and butorphanol (ALF-AB), propofol (PRO) and propofol+AB (PRO-AB). AB doses were standardized. Dogs were anesthetized 5 minutes later by administration of alfaxalone or propofol IV to effect. Arytenoid motion during maximal inspiration and expiration was captured on video before and after IV doxapram (0.25 mg kg-1). The change in rima glottidis surface area (RGSA) was calculated to measure arytenoid motion. An investigator blinded to the treatment scored laryngeal examination quality. RESULTS: A 20% increase in RGSA was the minimal arytenoid motion that was detectable. RGSA was significantly less in ALF before doxapram compared with all other treatments. A <20% increase in RGSA was measured in eight of 10 dogs in PRO and in all dogs in ALF before doxapram. After doxapram, RGSA was significantly increased for PRO and ALF; however, 20% of dogs in PRO and 50% of dogs in ALF still had <20% increase in RGSA. A <20% increase in RGSA was measured in five of 10 dogs in PRO-AB and ALF-AB before doxapram. All dogs in PRO-AB and ALF-AB with <20% increase in RGSA before doxapram had ≥20% increase in RGSA after doxapram. Examination quality was significantly better in PRO-AB and ALF-AB. CONCLUSIONS AND CLINICAL RELEVANCE: The use of acepromazine and butorphanol improved the quality of laryngeal examination. Any negative impact on arytenoid motion caused by these premedications was overcome with doxapram. Using either propofol or alfaxalone alone is not recommended for the evaluation of arytenoid motion.

Evaluation of an intramuscular butorphanol and alfaxalone protocol for feline blood donation: a pilot study.

Objectives The purpose of this pilot study was to evaluate the use of an intramuscular (IM) sedation protocol with butorphanol and alfaxalone in cats undergoing blood donation. We hypothesized that this drug combination would provide sufficient sedation to perform phlebotomy without causing hypotension or significant changes in heart rate. Methods Six purpose-bred, healthy adult cats were sedated using IM butorphanol (0.4 mg/kg) and alfaxalone (2-3 mg/kg). Pulse and Doppler blood pressure (BP) were recorded at baseline, after sedation and immediately following phlebotomy. Once laterally recumbent, 12 ml/kg blood was collected from the jugular vein. Sedation scores, duration of lateral recumbency and the ability to successfully perform phlebotomy were recorded. Results There was no significant change in heart rate post-sedation (median 190 beats per min [bpm], range 160-224 bpm) or post-phlebotomy (median 200 bpm, range 180-220 bpm) compared with baseline values (median 200 bpm, range 180-220 bpm) ( P = 0.395). A statistically significant change in BP was detected ( P = 0.029), attributed to a difference between post-sedation (median 113.3 mmHg, range 110.7-130.0) and baseline (median 133.3 mmHg, range 130.0-183.3) measurements. Hypotension was not observed in any cat. Collection of at least 80% of the target volume was achieved in 5/6 cats, although all were adequately sedated to allow jugular venous phlebotomy. Median recumbency time was 53 mins (range 43-83 mins). Phlebotomy duration lasted a median of 13 mins (range 5-21 mins). Conclusions and relevance The administration of IM alfaxalone and butorphanol provided sufficient restraint for blood donation without causing hypotension or significant changes in heart rate before or after phlebotomy.

Postoperative Analgesia Provided by Liposomal Hydromorphone in Client-Owned Dogs Undergoing Limb Amputation.

The analgesic efficacy of liposomal hydromorphone (LE-hydro) was tested in dogs undergoing limb amputation. The positive controls (n = 10) received subcutaneous (SQ) hydromorphone (0.2 mg/kg) and 1.5 mL of blank liposomes before surgery; fentanyl continuous rate infusion (CRI), 5-10 µg/kg/hr IV, during and for 24 hr after surgery; and a fentanyl patch at extubation. The negative controls (n = 7) received SQ hydromorphone (0.2 mg/kg) and 1.5 mLs of blank liposomes SQ before surgery, fentanyl CRI (5-10 µg/kg/hr IV) during surgery but stopped at extubation, and a fentanyl patch at extubation. The test group (n = 11) received 3 mg/kg of LE-hydro and 1.5 mL of saline SQ before surgery, 1.5 mL of saline SQ, and a saline CRI during surgery. All groups received a bupivacaine block in the limb prior to amputation and carprofen prior to surgery. Treatment failures, pain scores, opioid side effects, heart rate, respiratory rate, temperature, and client-reported pain and side effects were evaluated. There were three treatment failures in the positive control (3/10) and test groups (3/11). Negative controls had seven treatment failures (7/7). Side effects for all three groups were within expected limits. LE-hydro provides postoperative analgesia equivalent to fentanyl CRI in dogs undergoing limb amputation.

ANESTHETIC INDUCTION AND RECOVERY PARAMETERS IN BEARDED DRAGONS (POGONA VITTICEPS): COMPARISON OF ISOFLURANE DELIVERED IN 100% OXYGEN VERSUS 21% OXYGEN.

Inland bearded dragons (Pogona vitticeps, n=6) were anesthetized for 1 hr using isoflurane in either 100% oxygen or 21% oxygen (FI 21; medical-grade room air). Parameters of anesthetic depth were recorded throughout both induction and recovery by an observer blinded to the fraction of inspired oxygen (FiO2), including the loss and return of withdrawal and righting reflexes, muscle tone, ability to intubate or extubate, and return to spontaneous respiration. Physiologic data were recorded every 5 min throughout the anesthetic procedures, including heart rate, body temperature, end-tidal CO2, hemoglobin oxygen saturation (SpO2), and percent expired isoflurane. Lizards were subjected to application of a noxious stimulus (needle stick) at 0, 30, and 60 min, and responses recorded. Following a minimum 7-day washout period, the experiment was repeated with each lizard subjected to the other protocol in a randomized, complete crossover design. The only statistically significant difference was a lower mean SpO2 in the group inspiring 21% oxygen (P<0.0020). No statistically significant differences were detected in any parameters during induction or recovery; however, all values were uniformly shorter for the FI 21 group, indicating a possible clinically significant difference. A larger sample size may have detected statistically significant differences. Further studies are needed to evaluate these effects in other reptile species and with the concurrent use of injectable anesthetic and analgesic drugs.

A comparison of cardiopulmonary function, recovery quality, and total dosages required for induction and total intravenous anesthesia with propofol versus a propofol-ketamine combination in healthy Beagle dogs.

OBJECTIVE: To compare cardiopulmonary function, recovery quality, and total dosages required for induction and 60 minutes of total intravenous anesthesia (TIVA) with propofol (P) or a 1:1 mg mL(-1) combination of propofol and ketamine (KP). STUDY DESIGN: Randomized crossover study. ANIMALS: Ten female Beagles weighing 9.4 ± 1.8 kg. METHODS: Dogs were randomized for administration of P or KP in a 1:1 mg mL(-1) ratio for induction and maintenance of TIVA. Baseline temperature, pulse, respiratory rate (fR), noninvasive mean blood pressure (MAP), and hemoglobin oxygen saturation (SpO2) were recorded. Dogs were intubated and spontaneously breathed room air. Heart rate (HR), fR, MAP, SpO2, end tidal carbon dioxide tension (Pe'CO2), temperature, and salivation score were recorded every 5 minutes. Arterial blood gas analysis was performed at 10, 30, and 60 minutes, and after recovery. At 60 minutes the infusion was discontinued and total drug administered, time to extubation, and recovery score were recorded. The other treatment was performed 1 week later. RESULTS: KP required significantly less propofol for induction (4.0 ± 1.0 mg kg(-1) KP versus 5.3 ±1.1 mg kg(-1) P, p = 0.0285) and maintenance (0.3 ± 0.1 mg kg(-1) minute(-1) KP versus 0.6 ±0.1 mg kg(-1) minute(-1) P, p = 0.0018). Significantly higher HR occurred with KP. Both P and KP caused significantly lower MAP compared to baseline. MAP was significantly higher with KP at several time points. P had minimal effects on respiratory variables, while KP resulted in significant respiratory depression. There were no significant differences in salivation scores, time to extubation, or recovery scores. CONCLUSIONS AND CLINICAL RELEVANCE: Total intravenous anesthesia in healthy dogs with ketamine and propofol in a 1:1 mg mL(-1) combination resulted in significant propofol dose reduction, higher HR, improved MAP, no difference in recovery quality, but more significant respiratory depression compared to propofol alone.

Comparison of carprofen and tramadol for postoperative analgesia in dogs undergoing enucleation.

OBJECTIVE: To compare analgesia provided by carprofen and tramadol in dogs after enucleation. DESIGN: Randomized, masked clinical trial. ANIMALS: 43 dogs. PROCEDURES: Client-owned dogs admitted for routine enucleation were randomly assigned to receive either carprofen or tramadol orally 2 hours prior to surgery and 12 hours after the first dose. Dogs were scored for signs of pain at baseline (ie, before carprofen or tramadol administration) and at 0.25, 0.5, 1, 2, 4, 6, 8, 24, and 30 hours after extubation. Dogs received identical premedication and inhalation anesthesia regimens, including premedication with hydromorphone. If the total pain score was ≥ 9 (maximum possible score of 20), there was a score ≥ 3 in any of 5 behavioral categories (highest score possible per category was 3 or 4), or the visual analog scale (VAS) score was ≥ 35 (maximum possible score of 100) combined with a palpation score > 0, rescue analgesia (hydromorphone) was administered and treatment failure was recorded. RESULTS: No differences were found in age, sex, or baseline pain scores between groups. Significantly more dogs receiving tramadol required rescue analgesia (6/21), compared with dogs receiving carprofen (1/22). Pain and VAS scores decreased linearly over time. No significant differences were found in pain or VAS scores between groups at any time point (dogs were excluded from analysis after rescue). CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study suggested that carprofen, with opioid premedication, may provide more effective postoperative analgesia than tramadol in dogs undergoing enucleation.

A comparison of epidural analgesia provided by bupivacaine alone, bupivacaine + morphine, or bupivacaine + dexmedetomidine for pelvic orthopedic surgery in dogs.

OBJECTIVE: To compare the analgesic efficacy of bupivacaine, bupivacaine + morphine, or bupivacaine + dexmedetomidine administered epidurally in dogs undergoing pelvic limb orthopedic surgery. STUDY DESIGN: Prospective, randomized, double blinded clinical trial. ANIMALS: Sixty dogs weighing (mean ± SD) 35 ± 15.7 kg, aged 5 ± 3 years. METHODS: Dogs were assigned to receive a lumbosacral epidural containing bupivacaine (B) 0.5%, 1 mg kg(-1) ; B, bupivacaine 0.5%, 1 mg kg(-1)  + morphine 1%, 0.1 mg kg(-1) ; B + M, or bupivacaine 0.5%, 1 mg kg(-1)  + dexmedetomidine 0.05%, 4 µg kg(-1) ; B + D. The anesthetic protocol was standardized. The median expired isoflurane concentration (E'Iso) and requirement for additional induction agent preventing purposeful movement were recorded. Pain was scored using visual analog (VAS) and modified University of Melbourne (UMPS) pain scales. Sedation was assessed using a 0-4 scale. All parameters were recorded preoperatively, and at extubation (t = 0), then at 1, 2, 4, 8, 12, 16, and 20-24 hours. Hydromorphone was administered postoperatively to patients with a VAS ≥ 35 and/or UMPS ≥ 9. Time to first voluntary urination and first motor activity were recorded. RESULTS: Postoperatively, B + D had a lower UMPS pain score than B at t = 1 hour (p = 0.013), but not compared to B + M. The B + D group had a shorter time to urination (p = 0.0131) and a longer time for return of motor function (p = 0.0068). There were no other differences between the treatments. CONCLUSION AND CLINICAL RELEVANCE: Epidurally administered B, B + M, or B + D in dogs all provided acceptable analgesia to manage post-operative orthopedic pelvic limb pain. Epidural administration of B + D is an effective alternative to the analgesia provided by B or B + M, but is associated with increased time to return of motor function. The direct neurotoxic effects of epidural dexmedetomidine have not been fully tested.

Pharmacokinetics of ammonium sulfate gradient loaded liposome-encapsulated oxymorphone and hydromorphone in healthy dogs.

OBJECTIVE: To evaluate the pharmacokinetics, in dogs, of liposome-encapsulated oxymorphone and hydromorphone made by the ammonium sulfate gradient loading technique (ASG). ANIMALS: Four healthy purpose-bred Beagles aged 9.5 ± 3.2 months and weighing 13.4 ± 2.3 kg. STUDY DESIGN: Randomized cross-over design. METHODS: Each dog was given either 4.0 mg kg(-1) of ASG-oxymorphone or 8.0 mg kg(-1) of ASG-hydromorphone SC on separate occasions with a 3-month washout period. Blood was collected at baseline and at serial time points up to 1032 hours (43 days) after injection for determination of serum opioid concentrations. Serum opioid concentrations were measured with HPLC-MS and pharmacokinetic parameters were calculated using commercial software and non-compartmental methods. RESULTS: Serum concentrations of oxymorphone remained above the limit of quantification for 21 days, while those for hydromorphone remained above the limit of quantification for 29 days. Cmax for ASG-oxymorphone was 7.5 ng mL(-1) ; Cmax for ASG-hydromorphone was 5.7 ng mL(-1) . CONCLUSIONS AND CLINICAL RELEVANCE: Oxymorphone and hydromorphone, when encapsulated into liposomes using the ammonium sulfate gradient loading technique, result in measureable serum concentrations for between 3 to 4 weeks. This formulation may have promise in the convenient use of opioids for clinical treatment of chronically painful conditions in dogs.

Evaluation of topical nalbuphine or oral tramadol as analgesics for corneal pain in dogs: a pilot study.

OBJECTIVE: To evaluate the effectiveness of topical nalbuphine or oral tramadol in the treatment of corneal pain in dogs. ANIMALS STUDIED: Fourteen male Beagle dogs. PROCEDURES: Dogs were divided into three treatment groups and sedated with dexmedetomidine (5 µ/kg IV). A 4 mm corneal epithelial wound was created in the right eye (OD) of all dogs. Sedation was reversed with atipamazole IM. All dogs received pre/post ophthalmic examinations. Post operatively, Group NB (n = 5) received topical 1% preservative-free nalbuphine OD q8 h and an oral placebo PO q8 h. Group TR (n = 5) received tramadol (4 mg/kg) PO q8 h and topical sterile saline OD q8 h. Group CNTRL (n = 4) received topical sterile saline OD q8 h and an oral placebo q8 h. All dogs received topical 0.3% gentamicin OD TID until healed. Dogs were pain scored using a pain scoring system modified from the University of Melbourne pain scale at 0, 1, 2, 4, and 6 h, then every 6 h by observers masked to treatment, until corneal wounds were healed. Treatment failure was recorded if cumulative pain scores were above a minimum threshold of acceptable pain and rescue analgesia of morphine (1.0 mg/kg IM) was administered subsequently. RESULT: Four dogs in Group NB, one dog in Group TR, and two dogs in Group CNTRL required rescue analgesia. There was no significant difference in the incidence of treatment failure between groups (P = 0.184). Mean time to rescue was 9.16 h. All corneal wounds were healed by 84 h. CONCLUSIONS: The results of this study suggest tramadol rather than nalbuphine should be further investigated for the treatment of corneal pain.

Epidural administration of liposome-encapsulated hydromorphone provides extended analgesia in a rodent model of stifle arthritis.

Liposome encapsulation of opioids by using an ammonium-sulfate-gradient loading technique significantly slows the release time of the drug. This study evaluated the duration of analgesia in a rodent model of monoarthritis after epidural administration of liposome-encapsulated hydromorphone (LE-hydromorphone; prepared by ammonium-sulfate-gradient loading) compared with standard hydromorphone and a negative control of blank liposomes. Analgesia was assessed by changes in thermal withdrawal latency, relative weight-bearing, and subjective behavioral scoring. Analgesia in arthritic rats was short-lived after epidural hydromorphone; increases in pain threshold were observed only at 2 h after administration. In contrast, thermal pain thresholds after epidural LE-hydromorphone were increased for as long as 72 h, and subjective lameness scores were lower for as long as 96 h after epidural administration. Injection of LE-hydromorphone epidurally was associated with various mild changes in CNS behavior, and 2 rats succumbed to respiratory depression and death. In conclusion, LE-hydromorphone prolonged the duration of epidural analgesia compared with the standard formulation of hydromorphone, but CNS side effects warrant careful administration of this LE-hydromorphone in future studies.

Respiratory rates and arterial blood-gas tensions in healthy rabbits given buprenorphine, butorphanol, midazolam, or their combinations.

The objective of this study was to evaluate the respiratory effects of buprenorphine, butorphanol, midazolam, and their combinations in healthy conscious rabbits. Six adult female New Zealand white rabbits were anesthetized briefly with isoflurane by mask to allow placement of a catheter into the central ear artery. After a 60-min recovery period, a baseline arterial sample was obtained. Animals then were injected intramuscularly with either 0.9% NaCl (1 mL), buprenorphine (0.03 mg/kg), butorphanol (0.3 mg/kg), midazolam (2 mg/kg), buprenorphine + midazolam (0.03 mg/kg, 2 mg/kg), or butorphanol + midazolam (0.3 mg/kg, 2 mg/kg). Arterial blood gases were evaluated at 30, 60, 90, 120, 180, 240, and 360 min after drug administration. All drug treatments caused significant decreases in respiratory rate, compared with saline. Buprenorphine and the combinations of midazolam-butorphanol and midazolam-buprenorphine resulted in statistically significant decreases in pO(2). No significant changes in pCO(2) pressure were recorded for any treatment. Increases in blood pH were associated with administration of butorphanol, midazolam, and the combinations of midazolam-butorphanol and midazolam-buprenorphine. In light of these results, buprenorphine and the combinations of midazolam-buprenorphine and midazolam-butorphanol result in statistically significant hypoxemia in rabbits that breathe room air. The degree of hypoxemia is of questionable clinical importance in these healthy subjects. Hypoxemia resulting from these drug combinations may be amplified in rabbits with underlying pulmonary or systemic disease.

Peginterferon with or without ribavirin has minimal effect on quality of life, behavioral/emotional, and cognitive outcomes in children.

UNLABELLED: The aim of this study was to prospectively assess the quality of life (QOL), behavioral/emotional functioning, and cognitive status of children undergoing treatment for hepatitis C virus (HCV) infection. In all, 114 children (5 to 18 years old) enrolled in a multisite randomized clinical trial (Peds-C) to evaluate peginterferon alpha 2a (PEG 2a) with ribavirin (RV) or with placebo (PL) completed several standardized measures prior to treatment and at 24 weeks, 48 weeks, 6 months following treatment, and at two annual follow-up visits. After 24 weeks of treatment, mean physical QOL scores declined significantly for both groups from baseline to 24 weeks of treatment (F = 5.8, P = 0.004), although scores remained in the average range. There were no significant time or group effects for behavioral/emotional or cognitive functioning. Three children (5%) in the PEG 2a + RV group and no children in the PEG 2a + PL group had a clinically significant increase in depression symptoms. For those children who received 48 weeks of treatment, there were no significant time or group effects on any of the outcome measures (P > 0.05). A majority of children in both the PEG 2a + RV and PEG 2a + PL groups experienced no clinically significant change in physical QOL, behavioral adjustment, depression, or cognitive functioning during or after treatment. CONCLUSION: Overall QOL and psychosocial functioning are not deleteriously impacted by PEG 2a + RV or PL treatment of children with HCV.

Antithrombin-heparin covalent complex reduces microemboli during cardiopulmonary bypass in a pig model.

Transcranial Doppler-detected high-intensity transient signals (HITS) during cardiopulmonary bypass (CPB) surgery have been associated with postoperative neurocognitive dysfunction, suggesting microemboli in the brain could be a contributing factor. HITS occur despite administration of unfractionated heparin (UFH). This study was done to determine whether antithrombin-heparin covalent complex (ATH), a more potent anticoagulant than heparin, can reduce HITS during CPB. In a pig CPB model, ATH, UFH, or UFH + antithrombin (AT) was intravenously administered to female Yorkshire pigs after sternotomy. Twenty minutes later, hypothermic CPB was initiated and continued for 1.25 hours, then normothermia was re-established for 45 minutes. Protamine sulfate was given to neutralize the anticoagulants, and pigs were allowed to recover. HITS were monitored using an arterial flow probe placed over the carotid artery. Compared with UFH (300 or 1000 U/kg), ATH reduced the number of HITS during CPB in a dose-dependent manner. AT (3 mg/kg) + UFH (300 U/kg) resulted in an intermediate HITS rate between UFH and ATH (2 mg/kg in terms of AT). Examination of brain sections for emboli formation confirmed that, similar to HITS, number of thrombi decreased in direct proportion to ATH dosage. These results support the hypotheses that the majority of HITS represent thromboemboli and that ATH reduces emboli formation during CPB.