Hypersensitivity of bladder low threshold, wide dynamic range, afferent fibres following treatment with the chemotherapeutic drugs cyclophosphamide and ifosfamide.

The cytotoxic drugs cyclophosphamide (CPO) and ifosfamide (IFO) cause toxic urological effects due to the production of urinary metabolites that cause bladder inflammation. This study aimed to identify changes in the bladder afferent system following treatment with these drugs that might explain reported urological adverse effects. Intravesical pressure and afferent nerve activity were recorded during bladder distension and drug administration in isolated bladders from mice, 24 h after intraperitoneal treatment with cyclophosphamide (100 mg/kg), ifosphamide (200 mg/kg) or saline (control). In isolated bladders, total afferent nerve activity at maximum bladder distension was increased from 182 ± 13 imp/s in control animals, to 230 ± 14 imp/s in CPO-treated (p < 0.05) and 226 ± 17 imp/s in IFO-treated (p < 0.001) mice. Single fibre analysis revealed the increase resulted from an enhanced activity in low threshold, wide dynamic range fibres (23.3 ± 1.9 imp/s/fibre in controls to 31.5 ± 2.5 (p < 0.01) in CPO and 29.9 ± 2.0 imp/s/fibre (p < 0.05) in IFO treated). CPO treatment was accompanied by an increase in urinary frequency in vivo, but was not associated with increases in urothelial release of ATP or acetylcholine, bladder compliance or spontaneous muscle activity. Also, CPO-treatment did not affect afferent nerve responses or pressure responses to purinergic, muscarinic or nicotinic agonists. This is the first report of CPO and IFO-induced changes in specific populations of bladder afferents, namely an increase in low threshold, wide dynamic range fibres. These effects appear to be direct and not secondary to increases in smooth muscle activity or the release of urothelial mediators.

Environmental sustainability in veterinary anaesthesia.

OBJECTIVE: Attention is drawn to the potential of global warming to influence the health and wellbeing of the human race. There is increasing public and governmental pressure on healthcare organisations to mitigate and adapt to the climate changes that are occurring. The science of anaesthetic agents such as nitrous oxide and the halogenated anaesthetic agents such as greenhouse gases and ozone-depleting agents is discussed and quantified. Additional environmental impacts of healthcare systems are explored. The role of noninhalational anaesthetic pharmaceuticals is discussed, including the environmental life-cycle analyses of their manufacture, transport, disposal and use. The significant role of anaesthetists in recycling and waste management, resource use (particularly plastics, water and energy) and engagement in sustainability are discussed. Finally, future directions for sustainability in veterinary anaesthesia are proposed. CONCLUSIONS: Veterinary anaesthetists have a considerable opportunity to drive sustainability within their organisations through modification of their practice, research and education. The principles of sustainability may help veterinary anaesthetists to mitigate and adapt to our environmental crisis. Due to their particular impact as greenhouse gases, anaesthetic agents should be used conservatively with the lowest safe fresh gas flow possible. Technologies for reprocessing anaesthetic agents are described.

Evaluation of a new handheld point-of-care blood gas analyser using 100 equine blood samples.

OBJECTIVES: To determine whether the Enterprise point-of-care blood analysis system (EPOC) produces results in agreement with two other blood gas analysers in regular clinical use (i-STAT and Radiometer ABL77) and to investigate the precision of the new machine when used with equine whole blood. STUDY DESIGN: Prospective, randomized, non-blinded, comparative laboratory analyser study. ANIMALS: Horses admitted to a university teaching hospital requiring arterial or venous blood gas analysis as part of their routine clinical management. METHODS: One hundred equine blood samples were run immediately, consecutively and in randomized order on three blood gas analysers. Results of variables common to all three analysers were tested for agreement and compared with guidelines used in human medicine. These require 80% of results from the test analyser to fall within a defined range or percentage of results from the comparator devices to achieve acceptability. Additionally, 21 samples were run twice in quick succession on the EPOC analyser to investigate precision. RESULTS: Agreement targets were not met for haematocrit, haemoglobin and base excess for either i-STAT or ABL77 analysers. EPOC precision targets were not met for partial pressure of carbon dioxide, ionized calcium, haematocrit and haemoglobin. Overall comparative performance of the EPOC was good to excellent for pH, oxygen tension, potassium, bicarbonate and oxygen saturation of haemoglobin, but marginal to poor for other parameters. CONCLUSIONS AND CLINICAL RELEVANCE: The EPOC may be useful in performing analysis of equine whole blood, but trend analysis of carbon dioxide tension, ionized calcium, haematocrit and haemoglobin should be interpreted with caution. The EPOC should not be used interchangeably with other blood gas analysers.

Comparison of sedation scores and propofol induction doses in dogs after intramuscular premedication with butorphanol and either dexmedetomidine or medetomidine.

OBJECTIVE: To compare sedation scores and propofol induction doses in dogs receiving either dexmedetomidine or medetomidine, both with butorphanol intramuscularly (IM) prior to general anaesthesia. STUDY DESIGN: Prospective, 'blinded', randomized, clinical study. ANIMALS: Fifty client-owned dogs scheduled for elective diagnostic imaging procedures. METHODS: Dogs were allocated to receive butorphanol 0.1 mg kg(-1) with either medetomidine (group M) 0.01 mg kg(-1) or dexmedetomidine (group D) 0.005 mg kg(-1) IM. Sedation was scored before and 20 minutes after pre-anaesthetic medication using a composite simple descriptive sedation score giving a score of 0 to 15 (0 = no sedation; 15 = profound sedation). Forty-five minutes after pre-anaesthetic medication, propofol was administered in increments of 0.5 mg kg(-1) over 15 seconds until tracheal intubation was possible. The time required to check intubation conditions between each propofol aliquot was 15 seconds. Total propofol dose required to perform tracheal intubation and the number of dogs achieving a clinically desired sedation score of ≥9/15 was recorded in each group. Sedation score and propofol dose were compared using the Mann-Whitney U-test. Results are reported as median (range). Statistical significance was set at p < 0.05. RESULTS: The sedation score 20 minutes after pre-anaesthetic medication was significantly higher in group M [11 (2-14)] than in group D [7 (0-14)]. There was no significant difference between propofol dose requirements in group M [1.5 (1-2.5) mg kg(-1)] or D at [1.5 (1-3) mg kg(-1)]. Significantly more dogs in group M achieved a sedation score of ≥9/15 than in group D. CONCLUSIONS AND CLINICAL RELEVANCE: Combined IM with butorphanol, medetomidine 0.01 mg kg(-1) produced effective sedation more frequently than dexmedetomidine 0.005 mg kg(-1) in dogs undergoing sedation prior to anaesthesia for elective procedures but this did not affect the propofol dose required for induction of anaesthesia significantly.

Acid-base and electrolyte balance following administration of three crystalloid solutions in dogs undergoing elective orthopaedic surgery.

OBJECTIVE: To compare acid-base balance and incidence of hyperchloraemic metabolic acidosis following administration of three crystalloid solutions to dogs undergoing anaesthesia for orthopaedic surgery. STUDY DESIGN: Prospective, randomised, clinical study. ANIMALS: Sixty dogs. METHODS: During a non-standardised anaesthetic, 0.9% saline (S), Hartmann's solution (H) or a polyionic glucose-free maintenance solution (M) was administered IV at 10 mL kg(-1)  hour(-1) . Venous blood pH, PCO2 , PCV, total protein, urea, sodium, potassium and chloride concentrations were measured at induction of anaesthesia (T0) and after 2 hours of fluid therapy (T2). Base excess (BE), bicarbonate, corrected chloride concentration (corrCl), osmolality, change in plasma volume (PV) and strong ion gap (SIG) were calculated. Changes in variables within groups (1-sample Student's t-test/Wilcoxon signed rank test) and between groups (1-way anova/Kruskal-Wallis) were assessed. Data are presented as median (interquartile range). Significance was set at p < 0.05. RESULTS: No significant differences existed between groups for pH, PCO2 , PCV, total protein, urea, potassium, corrCl, PV and SIG. Potassium significantly increased in all groups. Significant differences existed between groups S and M for BE, sodium, chloride, bicarbonate and osmolality, and between groups H and M for sodium and osmolality. Chloride concentration significantly changed from 116 (114-117) to 117 (116-119) mmol L(-1) in group S, 116 (115-118) to 115 (113-117) mmol L(-1) in group H and 116 (115-118) to 114 (113-118)  mmol L(-1) in group M. In groups H and M, sodium and osmolality decreased, and BE and bicarbonate concentration increased significantly. Plasma volume increased by 28 (14-44)%, 25 (5-40)% and 24 (13-33)% in groups S, H and M, respectively. CONCLUSION AND CLINICAL RELEVANCE: Hyperchloraemic metabolic acidosis did not develop after intraoperative 0.9% saline, Hartmann's solution or maintenance solution at 10 mL kg(-1)  hour(-1) for 2 hours in dogs undergoing elective orthopaedic surgery. Bicarbonate and BE increased after Hartmann's and maintenance solutions. Increases in potassium concentration were unexplained.

Intratesticular lidocaine reduces the response to surgical castration in dogs.

OBJECTIVE: To investigate whether intratesticular injection of lidocaine pre-surgery would reduce the intraoperative responses to elective castration in dogs. STUDY DESIGN: Double-blinded, randomized, controlled, prospective clinical study. ANIMALS: Forty-two client-owned dogs weighing 2.2-38.4 kg and aged between 4.5 and 56 months. METHODS: Group L dogs received an intratesticular injection of 2% lidocaine (2 mg kg(-1)) and Group S an identical volume of saline prior to surgery. Premedication was with acepromazine and morphine intramuscularly. Anaesthesia was induced with propofol intravenously and maintained with isoflurane vaporized in oxygen. Heart rate (HR), mean arterial pressure (MAP), respiratory rate (f(R)), end-tidal isoflurane (Fe'ISO) and carbon dioxide concentrations, oxygen saturation and ECG were monitored during surgery. Fe'ISO was maintained at 1.0±0.1%. Supplemental propofol was given in response to gross movement. RESULTS: Group L had significantly lower maximum values for both HR and MAP. Group L displayed significantly smaller increases in HR during exteriorization of the first testis than Group S. There was an overall significant difference in MAP between groups during all surgical events (p=0.041) and time points (p=0.002). In univariate analysis, Group L showed significantly less changes in MAP during skin incision, exteriorization of the first testis and clamping of both spermatic cords. Group S reached its highest f(R) significantly earlier. Group L (eight dogs) required additional propofol 33±18 minutes after the start of surgery and Group S (seven dogs) at 19±17 minutes; this difference was not statistically significant. Seven dogs in Group L and 12 dogs in Group S required rescue analgesia with morphine (GCMPS-SF score ≥6); this difference was not statistically significant. No adverse effects were reported postoperatively. CONCLUSIONS AND CLINICAL RELEVANCE: Based on this study, the authors recommend the use of intratesticular lidocaine for surgical castration in dogs.

Recognition of depressive disorders by primary care providers in a military medical setting.

This study examined the accuracy of military primary care providers in detecting depressive disorders in their patients. For a 5-day period, each patient who entered the primary care clinic completed the depression section of the Patient Health Questionnaire (PHQ). Appointment notes were examined for depressive disorder diagnoses and then compared with PHQ responses. Of 337 respondents, 19 (5.6%) were identified by the PHQ as meeting the criteria for major depression; 4 (21%) of these 19 were identified by their provider as having a major depressive disorder. Eighteen (5.3%) were identified as having minor depression by the PHQ; none of these individuals were identified by their provider as having minor depression. These results suggest that military primary care providers, like their civilian counterparts, are not diagnosing depressive disorders as frequently as they present. Given the financial, medical, and personal consequences of not recognizing and treating depressive disorders, suggestions for increasing appropriate depression diagnoses are discussed.