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The objective of this clinical study was to establish for the first time a quantitative assessment of analgesia under practice common general anaesthesia of pigs induced by Ketamine-Azaperone using electromyography (EMG) to record the Nociceptive Flexor Reflex (NFR) but also using Elektroencephalography (EEG) to derive the Bispectral Index (BIS), both under surveillance of the previous traditional pain specific defense behaviour. In case of suitability the NFR should be applied also to test the Interdigital Claw Reflex (ZKR) which is in practice commonly used to assertain surgical tolerance before operations. Furthermore, the possibility to control the consciousness in pigs with aid of the BIS should be investigated for the first time, too.
With the NFR and the blood levels of Ketamine, Norketamine and Azaperone it should be checked, if Cortisol can function as a reliable parameter for pain or stress during Ketamine-Azaperone-anaesthesia.
Possible negative side effects of the anaesthesia on heart, cardiovascular system and respiration, particularly the risk of catalepsis by Ketamine should be controlled in addition.
As a model for monitoring somatic and visceral analgesia the castration of 30 clinically healthy male pigs with a body weight between 42 and 60 kg was used.
As somatic and visceral pain stimuli served the incision of the scrotal skin, of the tunica vaginalis and of the testis, the draw, the squeezing and the cutting off the spermatic cord with an emasculator, and finally the disinfection of the wound.
The general anaesthesia was induced with an initial intramuscular dose of 20 mg/kg Ketamine (Ursotamine®) and 2 mg/kg Azaperone (Stresnil®).
Right after laying down the NFR was recorded every minute using the EMG of the deltoid muscle. Additional records were taken exactly at the time of a certain manipulation or a specific pain stimulus.The stimulation of the NFR was performed by electric irritation of the ulnar nerve distal from the carpal joint.The irritation consisted of five terms of 0.5 s distance, each, with five square impulses of 1 ms duration and a distance of 4 ms. The strength of irritation was limited to 45 mA. The threshold for nociception of 40 ?V was determined from the arithmetic mean of the baseline-rushing (15 ?V) plus it´s sixfold standard deviation. For control of consciousness and/or analgesia the BIS was evaluated from current EEG derivation of the frontal region. The serum concentrations of Cortisol, Ketamine and Azaperone were determined in 13 pigs with ear vein catheters before and during surgery, and up to four hours afterwards with the Liquid Chromatography coupled Mass Spectrometry (LC-MS).
The pain-specific defense behaviour was evaluated using a standardized semi-quantitative scoring on the basis of defense-movements and vocalization. The lack of both is defined as surgical tolerance (Score 0).
The ZKR was manually tested as common in practice. The vital parameters oxygen saturation, end-tidal carbon dioxide saturation, heart rate, mean arterial pressure and respiratory rate were currently recorded using the usual surveillance equipment in human anaesthesiology.
To control catalepsis the EMG was also currently recorded from the deltoid muscle using another record channel.
As an important result the NFR monitoring demonstrated that the initial dosage of Ketamine-Azaperone interrupts the conduction of pain signals to the effectors (muscles) following somatic as well as visceral pain stimuli. Related to surgical tolerance (Score 0) the test sensitivity and specifity of the NFR were 93% and 98%. Post operationem, up to two hours after inducing anaesthesia (maximum time of recording), a significant pain relief (74 ?V) was also shown by NFR, corresponding with Score 1.
The persistent high BIS values over time showed that this monitoring was not suited to estimate the state of analgesia and of consciousness in pigs. The vital parameters and Cortisol were also inappropiate indicators for analgesia. The test sensitivity and specifity of the ZKR with regard to the NFR-threshold (40 ?V) were 92% and 89%.
The EMG-values for control of catalepsis remained persistently on the low level of the baseline-rushing. All pigs demonstrated in accordance with this clinically an atonic muscle tone.
Even with repeated post-dosing of Ketamine (up to 60 mg/kg in total) no negative side effects were observed regarding the vital parameters. Only the respiratory rate during the monitoring was marginally above the reference range due to the central-stimulating effect of Ketamine.