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J Acupunct Meridian Stud 2022; 15(5): 314-321

Published online October 31, 2022 https://doi.org/10.51507/j.jams.2022.15.5.314

Copyright © Medical Association of Pharmacopuncture Institute.

Sedative Effect of Ketamin-Midazolam Administered at Acupoint GV20 Compared to Intramuscular Route in Blue-Fronted Amazon (Amazona aestiva): a Pilot Study

Aricia Noelli Brega Monteiro1,* , Bruno Simões Sérgio Petri2, Haroldo Furuya2 , Liliane Milanelo2 , Márcia Valéria Rizzo Scognamillo3, Ayne Murata Hayashi4

1Private Veterinary Acupuncture Practitioner, Cosmopolis, Sao Paulo, Brazil
2Centro de Recuperacao de Animais Silvestres (CRAS PET-TIETÊ) Parque Ecológico do Tiete, Sao Paulo, Brazil
3Private Veterinary Acupuncture Practitioner, Uberlândia, Minas Gerais, Brazil
4Department of Surgery, School of Veterinary Medicine, University of Sao Paulo, Sao Paulo, Brazil

Correspondence to:Aricia Noelli Brega Monteiro
Private Veterinary Acupuncture Practitioner, Cosmopolis, Sao Paulo, Brazil
E-mail aricia_monteiro@hotmail.com

Received: February 1, 2022; Revised: February 21, 2022; Accepted: July 11, 2022

This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background: The growth of exotic pet medicine is leading to fast developments in clinical investigations on birds. Acupuncture, specifically pharmacopuncture, offers safe chemical restraint options.
Objectives: To investigate pharmacopuncture at acupoint GV20 in blue-fronted Amazon parrots (Amazona aestiva) using ketamine and midazolam.
Methods: Sixteen healthy birds were distributed into four groups (C: intramuscular control; 1/2 C: 1/2 dose intramuscular control; 1/2 GV20: 1/2 dose at acupoint GV20; 1/5 GV20: 1/5 dose at acupoint GV20). Degree of sedation, latency, recuperation time, heart and respiratory rate, and body temperature were measured. Quantitative data were analyzed by a Student’s t-test.
Results: The C, 1/2 C, and 1/2 GV20 groups showed the same degree of sedation. The 1/2 GV20 group showed longer latency times (6 ± 2.1) than the 1/2 C (2.5 ± 0.5) group. Sedation time did not differ between the C (28 ± 9.8), 1/2 C (30.5 ± 8.6), and 1/2 GV20 (41 ± 22.24) groups. The 1/2 GV20 group recuperated faster (13.7 ± 3.7) than the C group (64.2 ± 3.5). The C and 1/2 C groups showed tremors and slow and unstable recovery. Two animals in the C group showed mild hypothermia (38°C).
Conclusion: The use of 1/2 GV20 was effective and safe to sedate blue-fronted Amazon parrots without side effects, providing easy, stable, and fast recovery. The use of 1/5 GV20 had a shorter sedation time. These findings show that the combination of acupuncture and drugs provides new possibilities for efficient anesthetic protocols with fewer side effects in birds.

Keywords: Acupuncture, Pharmacopuncture, Traditional chinese medicine, Parrot, Anesthesiology

INTRODUCTION

The increasing growth of exotic pet medicine, with its economic and ecological impact, is leading to fast developments in wildlife clinical investigation, especially on birds. The urban environment can cause stress in birds and increase admission rates to wildlife rescues and rehabilitation centers [1,2].

Therefore, anesthetic procedures for birds have become more important in veterinary practice. In this sense, it is important to have safe chemical restraint options, enabling physical and auxiliary tests and minimizing stress factors [3]. The combination of acupuncture and drugs provides new possibilities for efficient anesthetic protocols with fewer side effects.

Acupuncture is a noninvasive and safe treatment option, as well as a widely accepted technique for alleviating pain and inflammation. Reports on domestic animals and, recently, in south tortoises, penguins, toucans, and raptors, have observed that acupuncture can normalize appetite and digestion, modulate the immune system function, treat musculoskeletal and neurological diseases, and reduce behavior problems [4-10].

Acupoint injection is a modern acupuncture method. A saline solution, distilled water, autologous blood, vitamins, homeopathic drugs, ozone, bee venom, and herbal medicine extracts are injected at acupoints, providing a prolonged mechanical stimulus [11-16]. Recently, pharmacopuncture, i.e., the injection of subclinical doses of drugs at acupoints, has been implemented with successful results in veterinary practice. Pharmacopuncture in animals has been shown to produce similar effects as conventional doses of drugs in horses, pigs, dogs, and cats [17-21]. In mammals, the main acupoints used for drug injections are YinTang, GV16 and GV20 [12,18,19,21-27]. The sedative effect at GV20 can be associated with alpha-2-adrenergic system activation [18]. The GV20 anatomic location is at the intersection of the sagittal dorsal line and the line connecting the ears [28]. GV20 is called the Guan Ji Point in birds, “the meeting point of all Yang channels,” and its stimulation has been shown to treat mental distress [28].

To the best of our knowledge, there are currently no reports on avian pharmacopuncture. Therefore, this pilot study aims to investigate pharmacopuncture at acupoint GV20 in blue-fronted Amazon parrots (Amazona aestiva) using ketamine and midazolam as a low-cost anesthesia alternative for birds. This pilot study involves a small number of animals to test the logistics of a larger study and gain some preliminary information.

MATERIALS AND METHODS

Sixteen healthy adult blue-fronted Amazon parrots of unknown sex were included in this study. The birds were ringed for individual identification with a mean ± standard deviation body weight of 0.358 ± 0.615 kg (Fig. 1).

Figure 1. Slight physical restraint for weighing at blue-fronted Amazon parrot (Amazona aestiva).

The parrots were temporarily housed at the wild animal center of “Parque Ecológico do Tietê” (CRAS-PET) in São Paulo, SP, Brazil, before release. All the parrots underwent routine physical examinations and were considered in good health. The parrots were maintained in flocks of 16-20 enclosed birds. During the study, the parrots were individually housed in plastic cages for visual evaluation (Fig. 2).

Figure 2. Blue-fronted Amazon parrots (Amazona aestiva) individually housed in plastic cages for visual evaluation.

Study design

All the birds were randomly assigned to one of four treatments: 1) Drug Control (C), ketamine (15 mg/kg) and midazolam (1 mg/kg) injected into the pectoral muscle mass; 2) Half dose control (1/2 C), 50% ketamine (7.5 mg/kg) and midazolam (0.5 mg/kg) injected into the pectoral muscle mass; 3) Pharmacopuncture half dose (1/2 GV20), 50% ketamine (7.5 mg/kg) and midazolam (0.5 mg/kg) injected subcutaneously at acupoint GV20; 4) Pharmacopuncture 20% dose (1/5 GV20), 20% ketamine (3 mg/kg) and midazolam (0.2 mg/kg) injected subcutaneously at acupoint GV20 located at the intersection of the sagittal dorsal line and the line connecting the two ears (Fig. 3).

Figure 3. Pharmacopuncture in at acupoint GV20 in a blue-fronted Amazon parrot (Amazona aestiva).

The chosen dose is commonly used in clinical avian veterinary practice. The injections were performed using 6 mm × 0.25 mm (13G) hypodermic needles. Total experimental time was defined as the recuperation time for each animal to stay upright. In each set of experiments, four animals were observed by four blind evaluators. All behavioral responses were recorded in a behavior form (Appendix 1). The degree of sedation, latency, recuperation time, heart and respiratory rate, and body temperature were measured. The quantitative data were analyzed using a Student’s t-test. The degree of sedation was evaluated according to an adapted descriptive numeric scale (Table 1) [29].

Table 1

Alertness score for sedation evaluation.

SedationParametersGrade
SatisfactoryClosed eyes, decubitus, no movement, and muscle relaxation.0
ModerateLight signs of tranquilization, possible decubitus, open eyes, responsive to stimulus.1
AbsentStanding position, open eyes, responsive to stimulus.2

RESULTS

The C, 1/2 C, and 1/2 GV20 groups showed the same sedation degree (Fig. 4). In each group, three animals presented satisfactory sedation, and one had moderate sedation (Fig. 5A and 5B). Only one animal in the 1/5 GV20 group had satisfactory sedation, one had moderate sedation, and two had no sedation (Fig. 5C).

Figure 4. Pharmacopuncture-induced degree of sedation in blue-fronted Amazon parrots (Amazona aestiva).
Figure 5. Degree of sedation in blue-fronted Amazon parrots (Amazona aestiva). (A) Satisfactory sedation. (B) Moderate sedation. (C) Mixed sedation in Group 1/5 GV20: satisfactory sedation.

The C and 1/2 GV20 groups showed the same latency time (Table 2 and Fig. 6). The 1/2 GV20 group showed a longer latency time than the 1/2 C group, although both received the same dose of ketamine and midazolam (Table 2 and Fig. 6). The sedation time did not differ between the C, 1/2 C, and 1/2 GV20 groups (Table 2 and Fig. 6).

*p < 0.05..

&md=tbl&idx=2' data-target="#file-modal"">Table 2

Mean and standard deviation of latency time, sedation time, and recuperation time (in minutes) in blue-fronted Amazon parrots (Amazona aestiva).

ParameterGroupMean and standard deviation
Latency timeC4 ± 2.70
1/2 C2.5* ± 0.57
1/2 GV206* ± 2.16
1/5 GV205 ± 5.83
Sedation timeC28 ± 9.83
1/2 C30.5 ± 8.69
1/2 GV2041 ± 22.24
1/5 GV206.25 ± 7.32
Recuperation timeC64.25* ± 3.59
1/2 C27.5 ± 21.29
1/2 GV2013.75* ± 3.77
1/5 GV207.5 ± 10.37

*p < 0.05..


Figure 6. Pharmacopuncture mean values of latency, sedation, and recuperation time in blue-fronted Amazon parrots (Amazona aestiva).

The 1/2 GV20 group showed a faster recuperation time than the C group (Table 2 and Fig. 6). All animals from the C and 1/2 C groups showed tremors and had a slow and unstable recovery (Fig. 7). The 1/2 GV20 group had no adverse effects.

Figure 7. Unstable recuperation in a blue-fronted Amazon parrot (Amazona aestiva) after intramuscular administration of ketamine and midazolam.

DISCUSSION

The first evidence of veterinary acupuncture in China came from the Zhou Dynasty (1027 to 221 BC) when General Sun-Yang wrote the “Canon of Veterinary Medicine” (650 BC). However, it was not until 1825 that acupuncture was first used on a paralytic female dog at the Veterinary School of Alford [30-33]. Regardless of the abundant reports on the effect of acupuncture on domestic or experimental animals and humans, reports involving wild animals are rare [4-6,34-37]. Acupuncture is also not often described in birds and is mainly published as meeting abstracts and in a few case reports [7-10,38].

The sedative effects of pharmacopuncture are described in dogs, cats, and horses using several drugs and different acupoints. Xylazine pharmacopuncture at Yin Tang (10% of clinical doses) has been shown to induce sedation without bradycardia, cardiac arrhythmia, or emesis in dogs [24]. Acepromazine pharmacopuncture at GV1 (10% of clinical doses) has been shown to produce mild [12] to significant sedation in horses and reduce the mean heart rate and transport-induced increased heart rate at unloading during road transport [25].

Bird sedation is a routine technique and provides easier restraint, increasing the safety of clinical procedures [1,3]. Ketamine is one of the most used injectable anesthetics for most avian species [39]. The recommended dose for parrots is 10 to 50 mg/kg, requiring higher doses in smaller birds and longer recovery time in larger birds [40]. Ketamine injected intramuscularly has a latency period of three to five minutes and a duration of ten minutes. Complications, such as prolonged recovery, tremors, and poor muscle relaxation, are reported [39] Therefore, the combination of ketamine and sedatives, such as benzodiazepines (midazolam), is essential [41]. In turn, midazolam can cause muscle relaxation, though its duration is considered short [3]. When combined with ketamine, a dose of 0.2 to 4 mg/kg is recommended [40]. The combination of ketamine and midazolam is widely used in birds and recommended for short, minimally painful procedures or for anesthetic induction [42]. However, its application is questionable since its sedation period is short, and recovery is prolonged [43]. Thus, the present pilot study evaluated pharmacopuncture sedation effects in blue-fronted Amazon parrots using ketamine and midazolam. The C, 1/2 C, and 1/2 GV20 groups showed the same sedation degree, validating the use of half the recommended ketamine and midazolam dose at GV20 as an efficient anesthetic option with fewer side effects than traditional administration routes in blue-fronted Amazon parrots. Cost reduction is also an important aspect, as the most diverse birdlife resides in third world countries, mainly South America [44], where financial funds are scarce.

For mammals, 10 to 20% of the clinical dose for pharmacopuncture shows effective sedation [12,22-27]. In the present study, a 50% dose was needed to achieve the same sedation degree as in the control group. These results corroborate the sedative pharmacokinetics of birds, leading to the need for higher drug doses for traditional drug administration [1]. These results also corroborate the acupuncture theory in which birds are classified as warm and hyperactive species [5]. Indeed, mild sedation using pharmacopuncture (1/5 GV20) can be the first option for minor procedures like wing clipping and physical and imaging tests. As a clinical technique, a 20% clinical dose could be increased to 50% of the clinical dose if necessary. Therefore, there is a need for further studies to evaluate different drugs and acupoints for avian pharmacopuncture.

Systematic reviews show the use of pharmacopuncture on cervical pain, cancer-related symptoms (pain, ileus, hiccup, fever), and gastrointestinal signs. These reviews also show improved quality of life in human cancer patients [16,45,46]. However, few data are available on clinical indications for pharmacopuncture in animals [12,17-27].

Pharmacopuncture effects are directly related to acupoint specificity, i.e., correct acupoint selection and anatomical localization [17]. In this study, the easy access to GV20 facilitated injection and lessened the chance of error. GV20 pharmacopuncture is thus a new feasible adjuvant technique, executable even by non-acupuncturists for bird sedation.

The 1/2 GV20 group had a significantly higher latency time than the 1/2 C group (2.5 ± 0.57). This result was expected, as intramuscular absorption is faster than subcutaneous absorption, the pharmacopuncture route [17,24]. Despite the longer latency, the sedation degree was similar in both groups. The C (mean 4 ± 2.70 minutes) and 1/2 GV20 (6 ± 2.16 minutes) groups showed the same latency time, countersigning the acupoint action on drug effect [26]. Surprisingly, both the C and 1/2 C groups had the same sedation time.

This pilot study is limited by the small sample size. However, it was useful to obtain preliminary conclusions about the feasibility, cost, and outcome of pharmacopuncture in birds. The 1/2 GV20 group had a faster, calmer, and quicker anesthetic recovery (> 17 minutes), while the C and 1/2 C groups showed difficult and slow recuperation, with tremors and struggle [42,47]. Pharmacopuncture avoided these recovery complications and the risk of severe life‐threatening injuries in birds. Thus, pharmacopuncture is an effective route for blue-fronted Amazon parrot sedation, with fewer adverse effects than traditional drug administration routes.

Due to the multiplying and optimization effects of pharmacopuncture, it is necessary to reduce the dose to prevent the incidence of undesirable effects. For instance, the injection of total doses of dexmedetomidine at the GV20 of dogs was shown to increase the duration, degree of sedation, and analgesic effects. However, as expected, bradycardia was more significant in the acupuncture group [17].

In this study, all groups showed normal heart and respiratory rates. Two animals (50%) in the C group showed mild hypothermia (38°C), as expected. Hypothermia in birds leads to several changes in physiological parameters, such as bradycardia, low respiratory rate, bleeding, and death. Thus, GV20 pharmacopuncture is safe, reducing hypothermia risks, and is feasible in birds due to its easy access with usual physical restraint.

To our knowledge, this is the first study on pharmacopuncture at GV20 for sedation in birds. Further pharmacopuncture studies are needed to determine the optimal drug concentration and acupoint for maximal sedation without undesirable effects in blue-fronted Amazon parrots.

In conclusion, half the recommended dose of ketamine and midazolam at GV20 (1/2 GV20) was effective and safe to sedate blue-fronted Amazon parrots without side effects, providing easy, stable, and fast recovery. Twenty percent of the recommended dose at GV20 was also effective and safe and had a shorter sedation time in blue-fronted Amazon parrots without side effects. Therefore, these pharmacopuncture techniques can be useful for quick procedures, such as auxiliary tests. These findings are motivating, despite the small sample size, showing the need for further studies with larger sample sizes and different acupoints. Also, other bird species must be subjected to pharmacopuncture to evaluate the quality of sedation across all avians.

CONFLICT OF INTEREST

The authors declare no conflict of interest.

Fig 1.

Figure 1.Slight physical restraint for weighing at blue-fronted Amazon parrot (Amazona aestiva).
Journal of Acupuncture and Meridian Studies 2022; 15: 314-321https://doi.org/10.51507/j.jams.2022.15.5.314

Fig 2.

Figure 2.Blue-fronted Amazon parrots (Amazona aestiva) individually housed in plastic cages for visual evaluation.
Journal of Acupuncture and Meridian Studies 2022; 15: 314-321https://doi.org/10.51507/j.jams.2022.15.5.314

Fig 3.

Figure 3.Pharmacopuncture in at acupoint GV20 in a blue-fronted Amazon parrot (Amazona aestiva).
Journal of Acupuncture and Meridian Studies 2022; 15: 314-321https://doi.org/10.51507/j.jams.2022.15.5.314

Fig 4.

Figure 4.Pharmacopuncture-induced degree of sedation in blue-fronted Amazon parrots (Amazona aestiva).
Journal of Acupuncture and Meridian Studies 2022; 15: 314-321https://doi.org/10.51507/j.jams.2022.15.5.314

Fig 5.

Figure 5.Degree of sedation in blue-fronted Amazon parrots (Amazona aestiva). (A) Satisfactory sedation. (B) Moderate sedation. (C) Mixed sedation in Group 1/5 GV20: satisfactory sedation.
Journal of Acupuncture and Meridian Studies 2022; 15: 314-321https://doi.org/10.51507/j.jams.2022.15.5.314

Fig 6.

Figure 6.Pharmacopuncture mean values of latency, sedation, and recuperation time in blue-fronted Amazon parrots (Amazona aestiva).
Journal of Acupuncture and Meridian Studies 2022; 15: 314-321https://doi.org/10.51507/j.jams.2022.15.5.314

Fig 7.

Figure 7.Unstable recuperation in a blue-fronted Amazon parrot (Amazona aestiva) after intramuscular administration of ketamine and midazolam.
Journal of Acupuncture and Meridian Studies 2022; 15: 314-321https://doi.org/10.51507/j.jams.2022.15.5.314

Table 1 . Alertness score for sedation evaluation.

SedationParametersGrade
SatisfactoryClosed eyes, decubitus, no movement, and muscle relaxation.0
ModerateLight signs of tranquilization, possible decubitus, open eyes, responsive to stimulus.1
AbsentStanding position, open eyes, responsive to stimulus.2

Table 2 . Mean and standard deviation of latency time, sedation time, and recuperation time (in minutes) in blue-fronted Amazon parrots (Amazona aestiva).

ParameterGroupMean and standard deviation
Latency timeC4 ± 2.70
1/2 C2.5* ± 0.57
1/2 GV206* ± 2.16
1/5 GV205 ± 5.83
Sedation timeC28 ± 9.83
1/2 C30.5 ± 8.69
1/2 GV2041 ± 22.24
1/5 GV206.25 ± 7.32
Recuperation timeC64.25* ± 3.59
1/2 C27.5 ± 21.29
1/2 GV2013.75* ± 3.77
1/5 GV207.5 ± 10.37

*p < 0.05..


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