Systemic and anti-nociceptive effects of prolonged lidocaine,ketamine, and butorphanol infusions alone and in combination in healthy horses

Background

Prolonged drug infusions are used to treat horses with severe signs of pain, but can be associated with altered gastrointestinal transit. The purpose of this study was to determine the effects of prolonged constant rate infusions (CRI) of lidocaine (L), butorphanol (B), and ketamine (K) alone and in combination on gastrointestinal transit, behavior, and thermal nociceptive threshold in healthy horses.

Methods

Eight healthy adult horses were used in a randomized, cross-over, blinded, prospective experimental trial. Interventions were saline, L, K, B, LK, LB, BK, and LBK as an intravenous CRI for 96 hours. Drugs were mixed or diluted in saline; following a bolus, CRI rate was 0.15mL/kg/hr with drug doses as follows: L – 1.3 mg/kg then 3 mg/kg/hr; B – 0.018 mg/kg then 0.013 mg/kg/hr; K – 0.55 mg/kg then 0.5 mg/kg/hr. Two-hundred plastic beads were administered intragastrically by nasogastric tube immediately prior to the bolus. Feces were collected every 2 hours, weighed, and beads manually retrieved. Behavior was scored every 2 hours, vital parameters every 6 hours, and thermal nociceptive threshold every 12 hours for 96 hours. Drug concentrations in the LBK solution were tested every 6 hours for 72 hours.

Results

Four of 64 trials (3 LBK, 1 BK) were discontinued early due to signs of abdominal discomfort. There were no apparent differences between groups in vital parameters or thermal threshold. Transit time was delayed for LB and LBK with a corresponding decrease in fecal weight that was most severe in the final 24 hours of infusion. Significant changes in behavior scores, vital parameters, or thermal threshold were not observed. The concentration of each drug in the combined solution declined by less than 31% over the sampling period.

Conclusions

Drug combinations containing butorphanol cause an apparent delay in gastrointestinal transit in healthy horses without substantially affecting somatic nociception at the doses studied. Combinations of lidocaine and ketamine may have less impact on gastrointestinal transit than infusions combined with butorphanol. Further work is needed to determine the effects of these drugs in painful or critically ill patients.

     

Effect of midazolam and butorphanol premedication on inhalant isoflurane anesthesia in mice

Isoflurane is a representative inhalant anesthesia used in laboratory animals. However, isoflurane mediates respiratory depression and adverse clinical reactions during induction. In the present study, we established a novel balanced anesthesia method in mice that combined isoflurane anesthesia with midazolam and butorphanol (MB). Thirty-four male C57BL/6J mice received either isoflurane alone or isoflurane with an intra-peritoneal MB premedication (3 mg/kg midazolam and 4 mg/kg butorphanol). The minimum alveolar concentration (MAC) in each group was evaluated. Induction time and adverse clinical reactions were recorded in each group. Core body temperature, heart rate, respiratory rate, and oxygen saturation (SPO₂) were assessed before and for 1 h after induction. Premedication with MB achieved a significant reduction in MAC compared with isoflurane monoanesthesia (isoflurane, 1.38 ± 0.15%; isoflurane with MB, 0.78 ± 0.10%; P<0.05). Induction time was significantly shortened with MB premedication, and adverse reactions such as excitement or incontinence were observed less frequently. Furthermore, isoflurane anesthesia with MB premedication caused increase of respiratory rates compared to isoflurane monoanesthesia. No significant decrease of SPO₂ was observed in MBI anesthesia, while a decrease in SPO₂ was apparent with isoflurane monoanesthesia (baseline, 98.3% ± 1.1; 10 min after induction, 91.8 ± 6.4%; P<0.05). In conclusion, premedication with MB was effective for the mitigation of respiratory depression induced by isoflurane in mice, with rapid induction and fewer adverse clinical reactions.     

Effect of sedation with detomidine and butorphanol on pulmonary gas exchange in the horse

Background  

Sedation with α₂-agonists in the horse is reported to be accompanied by impairment of arterial oxygenation. The present study was undertaken to investigate pulmonary gas exchange using the Multiple Inert Gas Elimination Technique (MIGET), during sedation with the α₂-agonist detomidine alone and in combination with the opioid butorphanol.     

The effect of daily repeated sedation using ketamine or ketamine combined with medetomidine on physiology and anesthetic characteristics in Rhesus Macaques

Background  Non-human primates are frequently sedated to permit handling that can alter physiological values. The purpose of this study was to identify the effects of daily serial sedation using ketamine (K) or ketamine combined with medetomidine (KM). We hypothesized KM would reduce observed effects of repeated sedation.
Methods  Eight rhesus macaques were anesthetized for three consecutive days. Physiological data were recorded daily at 5-minute intervals. Time intervals from injection to ataxia, recumbency, first movement and recovery were recorded. Depth of anesthesia was evaluated.
Results  Data showed an 11.7% increased heart rate at 5 minutes between the first and third day of injection with K and 17.9% with KM. Time from injection to ataxia increased 13.7% with K and 14.3% with KM. Time to recumbency increased 34.7% with K and 37.1% with KM.
Conclusion  These findings demonstrate repeated anesthesia with ketamine can initiate changes suggesting a tolerance effect.     

Safety and physiologic effects of intranasal midazolam and nitrous oxide inhalation based sedation in children visiting Saveetha Dental College and Hospitals,India

A large number of patients avoid dental care due to anxiety. Various techniques are available for behaviour related management. Therefore, safety and physiologic effects of intranasal midazolam and nitrous oxide inhalation based sedation in children aged 4 to 8 years visiting Saveetha Dental College and Hospitals, India is of interest. 35 anxious patients aged 4 to 8 years were included in the study. The patient received either intranasal midazolam/nitrous oxide in the first visit and vice versa at the second visit. The onset of sedation, recovery time and procedure duration were recorded using a timer. Physiological parameters were recorded using a monitor. Safety scale was used for assessing prevalence of adverse reactions. There was no significant difference between the groups in safety scale scores, recovery time and procedure duration. Midazolam group showed a statistically significant faster onset of sedation and a statistically significant increase in heart rate at four recorded time-points. All the vitals were within the physiological limits. Thus, intranasal midazolamis a safe alternative to nitrous-oxide sedation in completing the intended dental treatment while managing the anxious children in dental clinic.     

Effect of tongue position on postural stability during quiet standing in healthy young males

Abstract

Background and aims: Role of the neck and jaw sensory motor system in control of body balance has been established. Tongue is an integral part of jaw sensory motor system and helps in execution of purposeful and precise motor tasks like eating, drinking and speaking. The purpose of this study was to evaluate the possible effects of tongue position on the postural control system.

Materials and method: We compared the mean center of gravity (COG) velocity during quiet standing on an unstable surface with eyes closed during two test conditions: (i) with habitual jaw resting position and (ii) with instructed tongue positioned against the upper incisors. One hundred and sixteen normal healthy male subjects (average age 31.56?±?8.51 years and height 170.86?±?7.26?cm) participated in the study. Their COG velocity (deg/s) was measured using the NeuroCom® Balance Master version 8.5.0 (Clackamas, OR, USA).

Results and conclusions: The results show that COG velocity decreased significantly while tongue was positioned against upper incisors in comparison to the habitual jaw resting position. Our findings suggest that the tongue positioning can modulate postural control mechanisms. Tongue positioning against the upper incisors can enhance the postural stability during upright standing on an unstable surface and in the absence of vision in healthy young adults. Our findings can be of value for evaluation and rehabilitation protocols for postural control dysfunction.     

Effect of long-term bedrest on lower leg muscle activation patterns during quiet standing

It has been well known that balance instabilities after long-term exposure to microgravity (e.g., Anderson et al. 1986) or bedrest (BR) can be related to alterations and/or adaptations to postural control strategies. Little is known, however, how the reduced muscular activity affects the activation pattern of the lower limb muscles during quiet standing (QS). The purpose of this study was to investigate whether or not any changes in the lower limb muscle activation patterns during QS would occur after BR.     

Effects of ketamine sedation on glucose clearance,insulin secretion and counterregulatory hormone production in baboons (Papio hamadryas)

Since the effects of ketamine sedation seem to differ between subspecies of baboons, we assessed the endocrine response to an intravenous glucose tolerance test (IVGTT) in 12 hamadryas baboons. The first phase insulin secretion, basal insulin, and glucose levels, as well as the glucose clearance, were significantly lower in sedated baboons as compared to fully awake animals. Glucagon and Cortisol were significantly higher, while growth hormone was lower during ketamine sedation. Papio hamadryas appears to be a promising pre-clinical model for the study of endocrine replacement therapy in insulin-dependent diabetes. However, the data obtained must be interpreted with the knowledge that the anesthetic employed to allow for testing of the animals does have an effect on the parameters described in this report.     

Total intravenous anesthesia with midazolam, ketamine, and xylazine or detomidine following induction with tiletamine, zolazepam, and xylazine in red deer (Cervus elaphus hippelaphus) undergoing surgery

Sixteen captive female red deer were successfully anesthetized to surgically implant a telemetry system. The deer were immobilized with (mean±SD) 1.79±0.29 mg/kg xylazine and 1.79±0.29 mg/kg tiletamine/zolazepam given intramuscularly with a dart gun. Anesthesia was maintained for 69±2 min using a total intravenous protocol with a catheter placed in the jugular vein. Group X received xylazine (0.5±0.055 mg/kg/hr) and group D, detomidine (2±0.22 μg/kg/hr), both in combination with ketamine (2±0.02 mg/kg/hr) and midazolam (0.03±0.0033 mg/kg/hr), as a constant rate infusion. Anesthesia was reversed with 0.09±0.01 mg/kg atipamezole and 8.7±1.21 μg/kg sarmazenil given intravenously in both groups. These drug combinations provided smooth induction, stable anesthesia for surgery, and rapid recovery. Respiratory depression and mild hypoxemia were seen, and we, therefore, recommend using supplemental intranasal oxygen.     

Effect of ketamine on control of breathing in cats

We studied minute ventilation, breathing pattern, end-tidal CO2 partial pressure (PACO2), and tracheal occlusion pressure in cats anesthetized with ketamine (40 and 80 mg/kg) before and after CO2 inhalation. Before CO2 administration ventilation was reduced and PACO2 increased relative to unanesthetized cats at both ketamine doses. Breathing pattern was of the "apneustic" type, being characterized by 1) prolonged inspiratory duration and relatively short expiratory time and 2) markedly curvilinear (convex upward) inspiratory volume-time profile. The latter reflected a similar curvilinearity in the tracheal occlusion pressure waveform. During CO2 inhalation, the ventilatory response to CO2 was similar to that in unanesthetized cats in spite of a depressed tracheal occlusion pressure response. This discrepancy was due to the fact that in the presence of a convex upward inspiratory volume-time profile, the shortening of inspiratory duration with increasing CO2 results in a marked increase of mean inspiratory flow, and hence the ventilatory response to CO2 remains high.     

Effect of dopamine agonists or antagonists, TRH, stress and piglet removal on plasma prolactin concentrations in lactating gilts

The effect of dopamine agonists (ergocryptine), antagonists (chlorpromazine, haloperidol, reserpine, pimozide), thyrotropin releasing hormone or stress (restraint, piglet removal) on prolactin release was studied in primiparous lactating gilts. All animals were fitted with surgically implanted jugular catheters before farrowing. The only drug treatments which resulted in a significant change in PRL concentrations in blood were thyrotropin releasing hormone (increase) and ergocryptine (decrease). The results suggest that dopamine may not be the only regulator of prolactin in lactating pigs. Further studies are needed to identify drugs which would be useful in clinical situations for treatment of lactation failure due to low prolactin secretion. In the two stress-exposed groups, there was a gradual, steady decline in the plasma concentration of prolactin which resulted from loss of suckling contact with the piglets. Thus, snare restraint does not increase prolactin secretion in lactating sows confirming the results of other studies on pigs in different physiologic states.     

Effect of ski boot settings on tibio-femoral abduction and rotation during standing and simulated skiing

Ski boots are designed to transfer high forces from the skier to the ski. For this purpose they are made of stiff materials and constrain the leg of the skier to an unnatural position. To overcome the problem of unnatural knee posture, the ski boots can be adjusted in the frontal plane as well as in the horizontal plane by the canting mechanism and the "v-position", respectively. Canting enables lateral and medial orientation of the shaft with respect to the base of the boot. The "v-position" is a pronounced outward rotation of the boot's base with respect to the ski's long axis. The purpose of this study is to investigate the effect of different foot rotations and ski boot canting settings on knee kinematics during standing and simulated skiing. Knee kinematics was measured by means of motion analysis and with the help of skin-mounted markers on 20 subjects. The ski boots in their standard settings significantly constrained the skier to an unnatural valgus position. Ski boot base rotation had a significant effect on internal external knee rotation, whereas canting had an effect on varus-valgus angles during standing. However, for the simulated skiing position no effects were observed. The study suggests that the constraints of the ski boots result in a clinically relevant valgus misalignment. Canting settings reduced the misalignment but only by about 10%. Increased ski boot canting settings would therefore be desirable. Knee kinematics showed that rotational misalignment could not be linked to any significant increase in injury risk.     

Effect of carbostimulin on acid-base equilibrium of the blood of racing horses during exertion

The paper deals with possibility to regulate in a proper direction the acid-base state in race horse blood administering carbostimulin at rest and under physical exercises. The preparation is shown to favour an increase in alkaline blood reserves in race hours at rest and to prevent acidotic changes caused by physical exercises. The results obtained show a promising use of carbostimulin for the directed correction of the acid-base state of blood in race horses aimed at increasing the efficiency of the training process.     

Effect of exercise on iron metabolism in horses

We investigated the effect of exercise on iron metabolism in horses. Four horses were walked on a mechanical walker for 1 wk (pre-exercise). They then performed moderate exercise on a high-speed treadmill in the first week of the exercise and relative high in the second week and high in the third week. Serum iron was significantly lower in the third week of exercise than in the pre-exercise. Transferrin saturation (TS) was significantly lower in the first and third weeks of exercise than in the pre-exercise. Serum haptoglobin was significantly lower in the first week of exercise than in the pre-exercise and further significantly lower in the second and third weeks than in the first. The packed cell volume did not change during the experiment. The exercise significantly increased the apparent absorption of iron. Urinary iron excretion did not change throughout the experiment. Sweat iron loss did not change during the exercise. The exercise significantly increased iron balance. We considered that hemolysis is induced by moderate exercise and is further enhanced by heavy exercise, which decreases serum iron and TS. However, the increase in iron absorption compensates for the adverse effect of exercise on iron status. Therefore, exercise does not induce anemia in horses.     

Effect of alum on nitrification during simultaneous phosphorous removal in anoxic/oxic reactor

Phosphorus and nitrogen are the important eutrophication nutrients. They are removed in the anoxic/oxic reactor through simultaneous precipitation and biological nitrogen removal. The effect of alum a commonly used simultaneous precipitant on biological nitrification and denitrification are investigated in the present study. Simultaneous removal of phosphorus was carried out using the coagulant alum Al₂(SO₄)₃·14H₂O at 2.2 mol ratio. Before the start of simultaneous precipitation the nitrification rate of the A/O reactor was found to be 0.05 g N-NH₄ ⁺/g VSS/d. It starts to decrease with increase in coagulant dosage. The nitrification rate for alum dosage 97.13 mg/L was 0.38 g N- NH₄ ⁺/g VSS/d. There was no accumulation of nitrate in anoxic tank. The nitrogen removal efficiency of the reactor was affected and it fell from 88 to 78%. There was a slight decrease in effluent COD from 16∼20 mg/L to 8∼12 mg/L after the introduction of simultaneous precipitation into the reactor. The usage of alum as a simultaneous precipitant in the anoxic/oxic reactor was limited due to its inhibition on nitrification. Alum did not have any affect over denitrification process.