Analgesic efficacy of systemic ketamine and lignocaine for pre-emptive multimodal analgesia in dogs
Presently, there is no ideal analgesic protocol which is free of side effects to counteract central sensitisation and abolish pain in postoperative period. Opioids being frontline drugs for postoperative pain management possess clinically significant side effects such as respiratory depression, v...
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| Main Author: | |
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| Format: | Thesis |
| Language: | English |
| Published: |
2016
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| Online Access: | http://ethesis.upm.edu.my/id/eprint/17204/1/FPV%202016%2018%20T.pdf |
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| Summary: | Presently, there is no ideal analgesic protocol which is free of side effects to counteract
central sensitisation and abolish pain in postoperative period. Opioids being frontline
drugs for postoperative pain management possess clinically significant side effects such
as respiratory depression, vomiting, bradycardia and vasodilation. Recent findings
point towards preemptive multimodal analgesia as the way forward. Ketamine and
lignocaine are two potential drugs to be incorporated to an opioid-based protocol,
however, research related to their analgesic effects in dogs is limited. This study
evaluated the analgesic effects of systemic ketamine and lignocaine for postoperative
analgesia in dogs. Treatments were administered in a cross over design with one week
wash-out period. Analysis was performed using SAS software package. Data were
compared across treatments and time measurement using repeated- measures ANOVA
model and paired T test where two treatments were compared. Non parametric tests
were used when data were not normally distributed. In experiment one of this study,
effects of ketamine and lignocaine on electroencephalography (EEG) with electric
noxious stimulus under minimal anaesthesia model were studied. Ketamine at 3 mg/kg
intravenous (IV), loading dose (LD) and constant rate infusion (CRI) of 10 and 50
μg/kg/min, and lignocaine at 2 mg/kg followed by 50 and 100 μg/kg/min significantly
depressed the median frequency (MF) of EEG, an indicator of nociception.
Corresponding serum concentrations at the points of testing that depressed MF were
between 1898.41 ± 110.04 and 2100.59 ± 425.48 ng/ml for lignocaine and between
248.71 ± 75 and 641.35 ± 197 ng/ml for ketamine. In experiment two, an algometer
was modified, validated and subsequently used to determine mechanical nociceptive
thresholds in conscious dogs. In experiment three, ketamine alone at 0.5 mg/kg LD
followed by CRI of 30 μg/kg/min and 50 μg/kg/min, and ketamine at 30 μg/kg/min
with lignocaine at 2 mg/kg LD followed by 100 μg/kg/min significantly increased the
mechanical thresholds during the periods of infusion. Corresponding serum
concentrations of ketamine were found to be above 100 ng/ml. Thresholds returned to
baseline within 20 minutes following cessation of infusion and serum concentrations
were below 100 ng/ml. In experiment four, ketamine and lignocaine in addition to
tramadol at 4 mg/kg premedication was evaluated for preemptive multimodal analgesia
in dogs undergoing ovariohysterectomy. Results showed that the combination of
ketamine-lidocaine-tramadol obtunded intra-operative sympathetic responses better
than tramadol alone. The combination also attenuated primary hyperalgesia better than tramadol in the immediate 8 hours post-surgery, and tended to reduce secondary
hyperalgesia during the 72-hour postoperative study period. In conclusion, systemic
ketamine and lignocaine possess analgesic effects. Ketamine at serum concentrations of
> 100 ng/ml provided analgesia. Ketamine at 0.5 mg/kg LD followed by CRI at 30 or
50 μg/kg/min combined with lignocaine at 2 mg/kg LD followed by 100 μg/kg/min, is
safe for preemptive multimodal analgesia in dogs under anaesthesia. Preemptive
infusions of ketamine and lignocaine in addition to tramadol augmented analgesia,
likely, by attenuating intra-operative nociceptive inputs and reducing central
sensitisation. |
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