Multimodal Analgesia Protocol Using Continuous Infusion of Intravenous Morphine, Lidocaine and Ketamine in Dogs with Multiple Pelvic Fractures
A.R.C. Martins; D.M. Sakai; C.G.D. Lima; A.H. Oshiro; C.A.A. Valadão
Via de Acesso Prof. Dr. Paulo Donato Castellane, Jaboticabal, Brazil
Pain treatment has become very important in Veterinary Medicine. It is known that untreated animals may develop impairment in different systems. For instance, healing delays; reduction in immunity which can lead the patient to infectious diseases; impairment in gas exchange and therefore hypercapnia and hypoxemia; increase in myocardial oxygen consumption, since pain stress is related with higher levels of circulating catecholamines, which can also cause arrhythmias. Death can occur due to neurogenic shock (Otero 2005). Preventive analgesia has been used to reduce or prevent post-surgical pain (Fantoni 2005). This technique is based on the fact that analgesics drugs given before surgical procedure will prevent spinal cord neurons sensibilization and therefore reduction in the amount of post-surgical analgesics needed and a shorter recovery time (Fantoni & Mastrocinque 2005). Dissociative agents such as ketamine, act in sodium channels of both central and peripheric nervous systems and in voltage dependent calcium channels related to N-methyl-D-aspartic acid (NMDA) blocking glutamate in this receptor. These agents should not be used as a single analgesic agent and must be associated with other drugs (Otero 2005, Oliveira et al. 2004 & Fantoni et al. 2002). Lidocaine activates descending inhibitory pain pathways by binding to M3 muscarinic receptor; it also inhibits glycine receptors and promotes release of endogen opioids (Lauretti 2008). Opioid agents block the transmission of nociceptive signals according to the specificity, potency and efficacy in the different opioid receptors (μ, κ and δ). Morphine is an opioid μ-receptor agonist with high affinity op3 receptor and moderate spinal and supraspinal op 2 and op1 receptors (Otero 2005). Low dose morphine infusion is believed to decrease histamine release and minimal alveolar concentration (MAC) of volatile anesthetics (Muir III et al 2003). The use of multiple analgesic agents is also called multimodal or balanced analgesia (Kehlet & Dahl 1993). The use of drugs that act in different pathways, increase its efficacy and diminish its side effects (Woolf & Chong, 1993). Multimodal analgesia has been used both in human as well as veterinary medicine in order to prevent central sensibilization and chronic pain. Continuous infusions of analgesics maintain serum levels of these agents, avoiding plasmatic peaks which could lead to undesired side effects (Otero 2005). Pelvic fractures are frequent traumas both in dogs and cats and are complicated since this condition is often associated with abdominal and thoracic lesions. These fractures are usually associated with urinary bladder rupture; urethral rupture; rectum perforation; traumatic peripheric nerve lesion; prepubic tendon rupture and perineal laceration (Denny & Butterworth 2004). The purpose of this study was to evaluate the analgesic efficacy of continuous infusion on morphine, lidocaine and ketamine (MLK) before, during and after surgery in patients with multiple pelvic fractures.
Materials and Methods
After approval of the Ethics Committee of the Veterinary Hospital Governador Laudo Natel (HVGLN) of the Faculty of Veterinary Medicine--UNESP/Jaboticabal, four male and two female dogs of different breeds weighting from 5 to 12 kg underwent surgical procedure due to multiple pelvic fractures with soft tissue involvement, especially urinary tract lesions. Anesthesia was induced with 5 mg/kg-1 of intravenous propofol and general anesthesia was maintained with isoflurane. Continuous infusion of morphine (0.1 mg/kg-1 hour-1), lidocaine (0.05 mg/kg-1 hour-1) and ketamine (0.6 mg/kg-1 hour-1) in an electronic infusion pump, was started 30 minutes prior to the surgical procedure, during surgery and for three to four days after surgery. Infusion was paused for 2 hours before meals and restarted 2 hours after being fed. Since patients were fed twice a day, there was a total of 16 hours of MLK infusion during three days until hospital release. Collected data included: Visual Analogue Scale (VAS), Simple Descriptive Scale (SDS), heart rate (HR); respiratory frequency (RF); rectal temperature (RT); presence of pain obtained by pressure of the surgical site; pupil diameter (mydriasis, miosis or no alteration) and behavior (excited, calm or sedated). The VAS is a numeric with scores from o to 10, where 0 means no pain an 10 in the worst possible pain, according to the observer (Carvalho & Kowacs, 2006). The SDS is other pain assessment scale where 0 = no pain; 1 = light pain; 2 = moderate pain and 3 = severe pain (Mich & Helleyer 2008). Data were collected after patient admission in the hospital; 6 hours after the end of surgical procedure and every 24 hours until release from hospital. The data obtained from this study were analyzed according to its means and standard deviations.
Results
There was a consistent decrease both in VAS as well as in SDS scales, comparing the moment of the admission in the hospital and after the MLK treatment. According to this score all animals admitted had high levels of pain (mean value = 8) and after treatment all patients had a lower score of pain in different degrees. In a similar fashion, SDS values after MLK infusion was close to zero (no pain) in the end of treatment (four days).
One of the patients had a zero score right after the start of treatment. No animal had higher scores levels throughout the 4 days period. One of the patients had no desired answer to the MLK treatment and after 4 days this patient had a vocalization response when pressing the site of surgery. Since there is individual variation among patients and different degrees of lesions, animals should have an individual approach in pain treatment. This individual was prescribed 2 mg/kg-1 bid amitriptyline and showed a positive response. Sedation was observed only in two animals treated with MLK. One patient had hyporexia; other patient had an episode of emesis; both animals had an adjustment in the infusion rates and had clinical improvement. Heart rate and respiratory frequency decreased in all animals (Table 1), which was already expected, since the pain levels in the admission to the hospital were much higher than after MLK treatment. Pupil diameter had no relation to the pain scores.
Discussion and Conclusions
Despite being subjective evaluations both VAS e SDS have the advantages being of easy understanding, since the level of pain can be expressed as a numeric value. VAS is considered as a reliable parameter to evaluate if the analgesic treatment is being effective, if is being stable or if the pain level has gotten worsen (Mich & Hellyer 2008).
According to Mich & Hellyer 2008, although SDS has only 4 possible values, it is more accurate in the evaluation of pain than VAS. From this point of view, this study has a more positive result, since our SDS scores were much lower (close to zero in all animals) than VAS. Our study had a single observer, but we conclude that I would be more accurate more than one observer blind to the treatment in question. In future studies of multimodal analgesic treatment, more objective pain scales, such as Melbourne or Glasgow should be used. We concluded that the association of analgesic agents morphine, lidocaine and morphine in continuous infusion in dogs with multiple pelvic fractures associated with soft tissue lesions, provided less pain levels without sedation or severe side effects.
Table 1. Data obtained in patients with multiple pelvic fracture.
Comparative between parameters in the hospital admission (adm) and after treatment with morphine, lidocaine and ketamine (MLK).
VASadm
|
VASMLK
|
SDSadm
|
SDSMLK
|
HRadm
|
HRMLK
|
RFadm
|
RFMLK
|
RTadm
|
RTMLK
|
Animal 1
|
8
|
1.2 ± 0.84
|
2
|
0.4 ± 0.55
|
140
|
103 ± 4.47
|
39
|
14.8 ± 3.27
|
39
|
37.88 ± 0.53
|
Animal 2
|
10
|
6 ± 1.79
|
3
|
1.33 ± 0.82
|
160
|
135.83 ± 10.21
|
60
|
32.33 ± 8.71
|
39.6
|
38.52 ± 0.33
|
Animal 3
|
8
|
4.4 ± 1.67
|
2
|
0.6 ± 0.55
|
170
|
123.4 ± 5.27
|
57
|
19.4 ± 2.97
|
39.6
|
38.24 ± 0.38
|
Animal 4
|
7
|
0.4 ± 0.89
|
2
|
0 ± 0
|
139
|
104.2 ± 4.6
|
35
|
11.8 ± 2.05
|
38.5
|
38.62 ± 0.18
|
Animal 5
|
8
|
2.4 ± 1.34
|
2
|
0.4 ± 0.55
|
120
|
102.6 ± 4.88
|
56
|
22.6 ± 5.68
|
38.8
|
38.02 ± 0.33
|
Animal 6
|
8
|
3.2 ± 2.68
|
2
|
0.8 ± 0.84
|
180
|
123.2 ± 15.66
|
57
|
27.6 ± 5.32
|
39.4
|
38.18 ± 0.28
|
VAS = visual analogue scale; SDE = simple descriptive scale; hr = heart rate; RF: respiratory frequency; RT = respiratory frequency; adm = hospital admission; MLK = after treatment
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