The effect of different combinations of lignocaine,ketoprofen, xylazine and tolazoline on the acute cortisol response to dehorning in calves

AIMS: The aims of this study were (a) to evaluate the effect of xylazine and tolazoline, with and without lignocaine, on the cortisol response of calves following amputation dehorning and (b) to assess the effect of a non-steroidal anti-inflammatory drug (ketoprofen) and local anaesthesia on the cortisol response of calves to amputation dehorning.

METHODS: Plasma cortisol concentrations were measured in 100 dehorned or non-dehorned 3-month-old calves over an 8-h period following five different sedative/analgesic or control treatments. Sedative/analgesic treatments were: control (no anaesthesia); local anaesthesia and ketoprofen; local anaesthesia and xylazine; local anaesthesia, xylazine and tolazoline; and xylazine only. Within each sedative/analgesic treatment group, half the calves (n=10 per group) were amputation dehorned and half were not dehorned.

RESULTS: The change in plasma cortisol concentrations in calves dehorned after being given ketoprofen and local anaesthesia did not differ significantly from that of non-dehorned control calves for at least 8 h. In contrast, the cortisol response of dehorned calves not given analgesic drugs peaked 30 min after dehorning and lasted >4 h. Xylazine injected before dehorning significantly reduced but did not eliminate the peak of the cortisol response. When both xylazine and local anaesthesia were administered before dehorning the peak in the cortisol response was virtually eliminated. In the dehorned calves that received xylazine with or without local anaesthesia, cortisol concentration increased significantly 3 h after dehorning and did not return to baseline until at least 5 h later. When tolazoline was administered shortly after xylazine, it caused a marked cortisol response, higher than the response to any other treatment.

CONCLUSIONS: Combining ketoprofen and local anaesthesia minimised the cortisol response, and by inference the pain- induced distress, following amputation dehorning in calves. Xylazine reduced the initial cortisol response to dehorning but not as much as when local anaesthesia was also given. The increase in cortisol concentration from 3–8 h after dehorning in calves given xylazine alone or in combination with local anaesthesia suggests that calves experienced pain-induced distress during this time and that xylazine had no long-term analgesic effect. Tolazoline, used to reverse the sedative effects of xylazine, caused a marked cortisol response in calves via a mechanism which remains unclear.     

Effects of local anaesthesia of 4 to 8 hours duration on the acute cortisol response to scoop dehorning in calves

Objective To determine the effect of a long-acting local anaesthetic on the plasma cortisol response in calves dehorned using a scoop.
Design A physiological study with controls.
Procedure Seventy female calves, 3 to 4 months old, were divided into seven groups and dehorned by scoop with or without a long acting local anaesthetic (bupivacaine) which provides local anaesthesia for 3 to 4 h. In some treatment groups the local anaesthetic was given a second time, after 4 h, to give 8 h of anaesthesia. Blood samples were taken before and for 9 h after treatment and plasma cortisol concentrations were measured.
Results Scoop dehorning caused a marked rise in plasma cortisol concentration, which returned to pre-dehorning values after 7 h. The cortisol concentrations of calves given bupiva-caine were similar to those of control animals for 4 h after dehorning, but then a significant and protracted rise occurred, with concentrations returning to pretreatment values at about 9 h after dehorning. In calves given a second treatment of bupivacaine 4 h after dehorning, the plasma cortisol concentration remained similar to control values for 8 h after dehorning but then increased sharply.
Conclusions During its period of activity long-acting local anaesthetic prevented the rise usually seen after scoop dehorning in plasma cortisol concentrations; by inference it also alleviated the pain-induced distress caused by this procedure. However, when its effects had worn off the plasma cortisol values rose sharply indicating that animals still experienced pain-induced distress despite local anaesthetic being administered.     

Effect of local anaesthetic combined with wound cauterisation on the cortisol response to dehorning in calves

OBJECTIVE: To reassess whether local anaesthesia before dehorning and wound cauterisation after dehorning eliminates the cortisol response to dehorning. METHODS: A control group was compared with three dehorned groups (dehorned alone, dehorned after local anaesthesia, dehorned after local anaesthesia then cautery of the amputation wounds). The local anaesthetic regimen used produced nerve blockade for about 5 h. Blood samples were taken before and after dehorning and plasma cortisol concentrations were determined. RESULTS: Dehorning caused a marked cortisol response lasting for about 7 h. Local anaesthetic reduced the plasma cortisol concentrations to control values for 5 h, after which they increased for a further 5 h. Subsequently in both groups, cortisol concentrations remained at control values until at least 24 h after treatment. Local anaesthetic combined with wound cautery virtually abolished the cortisol response until at least 24 h after dehorning. CONCLUSION: Combining local anaesthesia with cautery of the amputation wounds substantially reduced the cortisol response until at least 24 h after dehorning.     

The utility of ketoprofen for alleviating pain following dehorning in young dairy calves

To determine if ketoprofen, in addition to local anaesthesia, reduces pain following dehorning, we experimentally dehorned dairy calves, less than 2 weeks of age, with (20 calves) or without (20 calves) intramuscular injections of ketoprofen. All calves received a local anesthetic (lidocaine) prior to dehorning and were dehorned with heat cauterization. Cortisol concentration was measured via jugular blood samples taken immediately before dehorning and at 3 and 6 hours following dehorning. Calf behavior was recorded between 0 and 2, 3 and 5, and 6 and 8 hours following dehorning. There was no significant (P > 0.10) effect on creep feed consumption, cortisol concentration, or any of the behavioral measures during the time periods studied. However, the difference in cortisol concentrations from the time of dehorning until 3 hours later was significantly lower (P < 0.05) in the ketoprofen-treated group. These results suggest that ketoprofen, in addition to local anesthesia, may alleviate short-term pain following dehorning with a butane dehorning device in dairy calves less than 2 weeks of age.     

Cortisol responses to dehorning of calves given a 5-h local anaesthetic regimen plus phenylbutazone,ketoprofen, or adrenocorticotropic hormone prior to dehorning

The purpose of this work was to assess whether the non-steroidal anti-inflammatory drugs (NSAIDs) phenylbutazone and ketoprofen, and an adrenocorticotropic hormone (ACTH) induced cortisol surge, reduce the cortisol response which occurs when the local anaesthetic wears off in calves following dehorning. There were four control groups and one dehorned group; also four groups were given local anaesthetic lasting 5h and were dehorned without or with phenylbutazone, ketoprofen or an ACTH injection, one group was injected with ACTH twice (at 0 and 6h) and another received ACTH and 6h later was dehorned. Blood samples were taken before and after dehorning and plasma cortisol concentrations were determined by radio-immunoassay. Dehorning increased the mean plasma cortisol concentrations [max 137 (11)nmoll(-1)] above control values [38 (5)nmoll(-1)] for about 7h, whereas local anaesthesia maintained concentrations at control values until about 5h after dehorning, and then they became elevated until about 10h. The maximum rise in mean concentration which occurred when the local anaesthetic wore off [128 (32)nmoll(-1)] was not affected when phenylbutazone was given before dehorning [141 (28)nmoll(-1)], but was reduced significantly when ketoprofen [65 (17)nmoll(-1)] or ACTH [61 (19)nmoll(-1)] were injected before or at the time of dehorning, respectively. Marked cortisol responses to ACTH injected at 0 and 6h were similar, but the early part of the cortisol response to dehorning 6h after an ACTH injection was reduced. It is suggested that the delayed cortisol response, which began 5h after dehorning, arose both from ketoprofen-sensitive and cortisol-sensitive sensory input as well as from other factors. Phenylbutazone did not affect the sensory input from the amputation wounds in the present calves.     

Effects of shallow scoop and deep scoop dehorning on plasma cortisol concentrations in calves

Scoop dehorning is one method of horn amputation. Plasma cortisol concentrations were used to investigate the effects of wound depth caused by shallow scoop and deep scoop dehorning on the acute pain-induced distress experienced by 15 week-old calves during the first 9 hours following horn amputation. Shallow scoop and deep scoop dehorning caused a prolonged cortisol elevation which returned to control values within 8 hours and 6 hours, respectively. There were no significant differences between shallow and deep dehorning with regard to mean plasma cortisol concentrations and integrated cortisol responses during the 9 hours after dehorning. Linear regression analysis revealed no significant correlation between wound depth and integrated cortisol response. Hence, at the investigated scoop wound depths, there was no detectable benefit in implementing a shallow scoop strategy in order to reduce acute pain-induced distress caused by scoop dehorning in 15 week-old calves.     

Halothane-sparing effect of xylazine in dogs and subsequent reversal with tolazoline

Halothane MAC (the minimum alveolar concentration of halothane to produce anaesthesia in 50% of the animals tested) was determined to be 0.92 ± 0.16 volumes % in eight English Pointer dogs. Alterations in halothane MAC induced by an intravenous bolus of xylazine (1.1 mg/kg) and then tolazoline (5 mg/kg) was determined in each dog following control (halothane MAC) measurement. Following xylazine administration, MAC significantly decreased to 0.57 ± 0.023%. Immediately following determination of the xylazine-halothane MAC value in each dog, tolazoline was administered and the halothane requirement (MAC) was again assessed. Halothane MAC significantly increased to 1.24 ± 0.036%. Tolazoline administration induced immediate arousal in the xylazine-halothane anaesthetized dogs requiring a rapid increase in halothane concentration to maintain anaesthesia. Thus, the administration of tolazoline, an alpha adrenergic antagonist, following xylazine administration significantly increased the anaesthetic requirement (MAC) of halothane. Xylazine, an alpha 2 adrenergic agonist, decreased halothane anaesthetic requirement (MAC) in the eight dogs studied. These results are consistent with the hypotheses that stimulation of central alpha 2 receptors is the mechanism by which xylazine produces sedation and that inhibition of CNS excitatory neurotransmitter release decreases halothane anaesthetic requirement. In contrast, the increase in halothane requirement and arousal from xylazine-halothane anaesthesia that occurred following i.v. tolazoline administration indicates an increase in CNS excitatory neurotransmitter activity.     

Acute cortisol responses of calves to scoop dehorning using local anaesthesia and/or cautery of the wound

Objective To measure plasma cortisol responses in calves dehorned using a scoop after administration of local anaesthesia and/or cautery of the wounds.
Design A physiological study with controls.
Procedure There were six treatments: control handling with and without local anaesthesia, dehorning, dehorning after local anaesthesia, dehorning followed by wound cautery, and dehorning after local anaesthesia followed by wound cautery. Blood samples were taken before and after dehorning.
Results Dehorning caused an increase in plasma cortisol concentrations, which decreased a little to plateau values and then declined to pretreatment values 3 to 4 h after dehorning. The peak was smaller after local anaesthesia was administered but when its effects wore off, cortisol concentrations increased and thereafter were similar to those in the dehorned animals. The combination of local anaesthesia and cautery resulted in a plasma cortisol response similar to those in control calves with or without local anaesthesia.
Conclusions If plasma cortisol concentrations reflect the distress being experienced by the calves, then local anaesthesia reduces the acute distress for about 3 h after dehorning but not during the subsequent 3 to 4 h. Combining local anaesthetic and cautery prevented the significant increase in plasma cortisol following dehorning and may eliminate the acute distress caused by scoop dehorning.     

Validation of the acute electroencephalographic responses of calves to noxious stimulus with scoop dehorning

AIM: To validate use of the electroencephalogram (EEG) and a minimal anaesthesia model for assessment of noxious sensory input caused by scoop dehorning of calves. METHODS: Twenty Friesian heifers weighing 125-178 kg were maintained under light general anaesthesia using halothane and an established protocol (minimal anaesthesia model). They were then dehorned using a scoop dehorner either with (DH+LA) or without (DH) a lignocaine ring block, and changes in the EEG and electrocardiogram (ECG) recorded. Median frequency (F50), 95% spectral edge frequency (F95) and total power (Ptot) were derived from the EEG data. RESULTS: There were significant increases in the F50 (p<0.01) and F95 (p<0.01), and a decrease in Ptot (p<0.01) following dehorning in the DH group, but there were no changes in the DH+LA group. Transient bradycardia in the first 75 sec following dehorning was recorded in the DH group compared with both pre-treatment values in the same group and with the DH+LA group (p<0.001). Tachycardia was evident by 15 min after dehorning in the DH but not the DH+LA group. CONCLUSIONS: The results validate use of the EEG and a minimal anaesthesia model for assessment of noxious sensory inputs in cattle.     

Effect of hot-iron disbudding on behaviour and plasma cortisol of calves sedated with xylazine

We investigated cortisol and behaviour for the first hour after hot-iron disbudding of calves aged 37 ± 4 days: disbudded after i/m xylazine (n = 10); disbudded after i/m xylazine and regional anaesthesia with lidocaine (n = 10); sham-disbudded after xylazine and lidocaine (n = 11); sham-disbudded after i/m saline and lidocaine (n = 10). Xylazine-treated groups had higher cortisol than saline-treated animals and showed no differences among them at any time. Sham-disbudded calves with xylazine had lower cortisol at 60 min compared with all other times. Xylazine-alone disbudded calves struggled more during the procedure than all other groups. Xylazine-alone disbudded calves showed more ear-flicks at 10, 25 and 40 min and head-shakes at 40 min than all other groups. We conclude that cortisol should not be used as an indicator of pain in disbudded calves while under the sedative effect of xylazine and that some behaviours during and after the procedure are useful in showing that xylazine alone does not control hot-iron disbudding pain.     

Attenuation of acute plasma cortisol response in calves following intravenous sodium salicylate administration prior to castration

Pain associated with castration in cattle is an animal welfare concern in beef production. This study examined the effect of oral aspirin and intravenous (i.v.) sodium salicylate on acute plasma cortisol response following surgical castration. Twenty bulls, randomly assigned to the following groups, (i) uncastrated, untreated controls, (ii) castrated, untreated controls, (iii) 50 mg/kg sodium salicylate i.v. precastration and (iv) 50 mg/kg aspirin (acetylsalicylic acid) per os precastration, were blood sampled at 3, 10, 20, 30, 40, 50 min and 1, 1.5, 2, 4, 6, 8, 10 and 12 h postcastration. Samples were analyzed by competitive chemiluminescent immunoassay and fluorescence polarization immunoassay for cortisol and salicylate, respectively. Data were analyzed using noncompartmental analysis, a simple cosine model, anova and t -tests. Intravenous salicylate V _d(ss) was 0.18 L/kg, Cl _B was 3.36 mL/min/kg and t _{1/2 λ} was 0.63 h. Plasma salicylate concentrations above 25  μ g/mL coincided with significant attenuation in peak cortisol concentrations ( P  = 0.029). Peak salicylate concentrations following oral aspirin administration was <10  μ g/mL and failed to attenuate cortisol response. Once salicylate concentrations decreased below 5  μ g/mL, cortisol response in the castrated groups was significantly higher than uncastrated controls ( P  = 0.018). These findings have implications for designing drug regimens to provide analgesia during routine animal husbandry procedures.     

Pharmacokinetics of xylazine, 2,6-dimethylaniline, and tolazoline in tissues from yearling cattle and milk from mature dairy cows after sedation with xylazine hydrochloride and reversal with tolazoline hydrochloride

Xylazine hydrochloride was administered i.m. at 0.35 mg/kg to 13 steers and 10 lactating dairy cows at Time 0. Ten minutes later, tolazoline hydrochloride was given i.v. at 4 mg/kg. Tissue and milk samples were analyzed using gas chromatography with nitrogen and phosphorous detection to determine concentrations of xylazine, 2,6-dimethylaniline (a toxic metabolite of xylazine), and tolazoline (at various intervals). Concentrations of xylazine and 2,6- dimethylaniline were below the limit of quantitation (10 microg/kg) by 72 hours in tissues and 12 hours in milk. The concentration of tolazoline was below 10 microg/kg by 96 hours in tissues and 48 hours in milk. Based on the results of these residue studies submitted by the sponsoring agency to the Ministry of Agriculture and Forestry in New Zealand, withholding periods for both xylazine hydrochloride and tolazoline hydrochloride injection were established.     

Influence of yohimbine and tolazoline on the cardiovascular, respiratory, and sedative effects of xylazine in the horse

To determine the effects of yohimbine and tolazoline on the cardiovascular, respiratory and sedative effects of xylazine, four horses were sedated with xylazine and treated with either yohimbine, tolazoline or saline. Xylazine was administered as an intravenous (i.v.) bolus (1.0 nig/kg) followed by a continuous infusion at the rate of 12 μg/kg/min. Heart rate, respiratory rate, mean arterial pressure, arterial blood gases, and the chin-to-floor distance were recorded throughout the experiment. After 60 min, either yohimbine or tolazoline was administered i.v. in incremental doses until reversal of sedation (defined as the return of the chin-to-floor distance to baseline values) was achieved. A control group in which a saline bolus was administered instead of an antagonist drug was included for comparison.
The average dose of yohimbine administered was 0.12 ± 0.02 (SEM) mg/kg. While the average dose of tolazoline was 7.5 ± 1.1 mg/kg. Both tolazoline and yohimbine antagonized the ventricular bradycardia and A-V conduction disturbances observed with xylazine administration. No change in mean arterial pressure was observed with xylazine or yohimbine administration, but tolazoline caused persistent mild systemic hypertension. There were no clinically significant changes in respiratory rate or arterial blood gas values with administration of either xylazine, yohimbine or tolazoline. The chin-to-floor distance decreased significantly with xylazine administration and increased significantly with administration of either yohimbine or tolazoline. In conclusion, both yohimbine and tolazoline successfully antagonized the cardiovascular and CNS depression associated with xylazine administration.     

Effects of local anaesthesia or local anaesthesia plus a non-steroidal anti-inflammatory drug on the acute cortisol response of calves to five different methods of castration

The cortisol response of calves to different methods of castration (ring, band, surgical, clamp) with or without local anaesthetic, or local anaesthetic plus a non-steroidal anti-inflammatory drug were recorded. All methods of castration caused a significant cortisol response and by inference pain and distress. Band castration caused a greater cortisol response than ring castration but the responses were eliminated by local anaesthetic. The cortisol response to surgical castration, by traction on the spermatic cords or by cutting across them with an emasculator, was not diminished by local anaesthetic but when ketoprofen was given with local anaesthetic the cortisol response was eliminated. Local anaesthetic did reduce the behavioural response to cutting the scrotum and handling the testes. Clamp castration caused the smallest cortisol response which was reduced or eliminated by local anaesthetic or local anesthetic plus ketoprofen respectively, but this method of castration was not always successful.     

The pharmacokinetics of ketamine administered intravenously in calves and the modifying effect of premedication with xylazine hydrochloride

Ketamine hydrochloride was administered intravenously to unpremedicated and xylazine-treated calves. The plasma concentrations of ketamine and norketamine were measured at several time intervals after drug administration and the data were fitted to a two-compartment open model. In unpremedicated female calves the distribution and elimination half-lives averaged 6.9 and 60.5 min, respectively. The volume of the central compartment was 1.21 1/kg and the peripheral compartment was 4.04 1/kg. Total body clearance of ketamine averaged 40.4 ml/ min/kg. Premedication with xylazine, whilst not affecting the half-lives signifi-candy, reduced volumes of distribution and the clearance rate of the drug by approximately 50%. The results for the male calves which were premedicated were intermediate between the two groups of female calves.     

Effects of ketoprofen alone or in combination with local anesthesia during the castration of bull calves on plasma cortisol,immunological, and inflammatory responses

To determine the effects of the anti-inflammatory ketoprofen, alone or with local anesthesia (LA) during castration on cortisol, immune, and acute phase responses, 40 Friesian calves (215 +/- 3.5 kg) were assigned as follows: 1) control, 2) surgical castration (SURG), 3) SURG following ketoprofen (3 mg/kg BW i.v.; SURG + K), 4) SURG following LA (9 mL of 2% lidocaine hydrochloride to each testis; SURG + LA), or 5) SURG following LA and K (SURG + LA + K). Total cortisol response was greater (P < 0.05) in SURG, SURG + LA, and SURG + K + LA calves than in control calves and was not different between control and SURG + K calves. The interval to peak cortisol was longer (P < 0.05) for SURG + K + LA calves than for either SURG or SURG + K calves. On d 3, KLH-induced interferon-gamma production was lower (P < 0.05) in SURG calves than in control calves, whereas concanavalin A-induced interferon-gamma production was lower (P < 0.05) in all castration groups than in control. On d 1 after surgery, fibrinogen was higher (P < 0.05) in SURG and SURG + LA calves than in control calves, whereas SURG + LA + K calves had lower (P < 0.05) fibrinogen than did SURG calves. Haptoglobin was higher (P < 0.05) in SURG calves on d 1, 3, and 7 than in control calves. On d 1 after surgery, SURG + K and SURG + LA + K calves had lower (P < 0.05) haptoglobin concentrations than SURG calves, whereas SURG + K calves had lower (P < 0.05) levels than SURG calves on d 3. In conclusion, surgical castration induced a significant elevation in cortisol secretion; the rise in cortisol was reduced to control levels by the administration of ketoprofen but not local anaesthetic. Thus, systemic analgesia using ketoprofen is more effective than local anesthesia during castration to alleviate the associated stress response.