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Effects of midazolam on ketamine-xylazine anesthesia in guinea fowl (Numida meleagris galeata).

Abstract: To determine the effect of midazolam on ketamine-xylazine anesthesia, 20 guinea fowl (Numida meleagris galeata) were randomly divided into 2 groups. Birds in group KX were anesthetized with ketamine (15 mg/kg IM) and xylazine (2.5 mg/kg IM), whereas the birds anesthetized in group KXM received midazolam (0.3 mg/kg IM) in addition to the ketamine and xylazine protocol. The onset of anesthesia, duration of analgesia, duration of recumbency, and recovery time were determined. Heart and respiratory rates as well as cloacal temperatures were recorded immediately after drug administration and at 10-minute intervals until the birds were sternally recumbent. Analgesia was assessed as a response to artery forceps applied to the digit and skin proximal to the tarsal joint. The mean (SD) duration of analgesia in the group KXM birds was 37.4 [+ or -] 23.5 minutes, whereas no analgesia was apparent with the group KX birds. The duration of recumbency was significantly longer and respiratory rates were significantly lower in group KXM birds compared with those in group KX. Adverse effects were minimal and included diarrhea (n = 1) and hypersalivation (n = 2) in group KX birds, and regurgitation (n = 2) in group KXM birds. Midazolam administered intramuscularly appeared to improve the anesthetic quality of ketamine and xylazine in guinea fowls without adversely affecting safety.

Key words: anesthesia, analgesia, midazolam, ketamine, xylazine, avian, guinea fowl, Numida meleagris galeata


Isoflurane inhalation anesthesia is the protocol of choice for most avian procedures; however, this methodology is not always feasible in the field. (1) Injectable anesthetics are used in birds to facilitate surgery and provide restraint for handling (2); advantages include rapid administration, low cost, and minimal equipment requirements. (3) Injectable agents that have been evaluated for use in birds include xylazine, medetomidine, ketamine, propofol, barbiturates, butorphanol, tiletamine-zolazepam, and alphadolone-alphaxolone. (4)

Ketamine has been widely used for anesthesia in many species, including nonhuman primates, cats, laboratory rodents, wildlife, and birds? Advantages include minimal cardiovascular depression and potential stimulation of cardiovascular function via the drug's sympathomimetic effect. (5,6) Ketamine can be administered intramuscularly or intravenously, which makes it practical for use in animals in which venous access is difficult. However, because its use can result in poor muscle relaxation, muscle tremors, myotonic contractions, opisthotonus, and rough recovery, ketamine is rarely used alone (7-10); it is often paired with drugs such as alpha-adrenergic agonists, benzodiazepines, and propofol for chemical restraint and induction of anesthesia in birds. (7,11-14)

Ketamine-xylazine combinations evaluated in several avian species are associated with increased blood pressure, decreased heart rate, and hypoxemia. (15,16) A ketamine-midazolam combination assessed in mallard ducks (Anas platyrhynchos) was associated with moderate sedation and only produced anesthesia and analgesia at very high dosages. (2) Thus, midazolam may improve the quality of anesthesia induced by a ketamine-xylazine combination in birds and also reduce the dosages required. In this study, we evaluated the effects of midazolam on the anesthetic properties and safety of a ketamine-xylazine combination in guinea fowl (Nurnida meleagris galeata).

Materials and Methods

Twenty adult guinea fowl of both sexes and with mean (SD) body weights of 1.13 [+ or -] 0.19 kg were used for the study. The birds were purchased from markets in Abeokuta, Nigeria, and housed in wooden cages. Before the study, the birds were prophylactically treated with gentamicin sulfate (7 mg/kg IM), because their health status was not determined at the time of purchase. Chicken grower ration and water containing soluble multivitamins were provided ad libitum for 5 days before the start of the study. Each bird was assessed to be in good general health based on physical examination findings and results of a complete blood count. The protocol for the study was approved by the Poultry Management Committee of the University of Agriculture, Abeokuta, Nigeria.

Food and water were withdrawn early in the morning before the study began. The 20 birds were randomly divided into 2 groups. The 10 birds in the first group (KX) were anesthetized with a combination of ketamine hydrochloride (15 mg/kg IM) and xylazine hydrochloride (2.5 mg/kg IM), and those in the second group (KXM) received midazolam (0.3 mg/kg IM) added to the same ketamine-xylazine protocol. Each drug was administered separately into the thigh muscle.

After induction of anesthesia, each bird was positioned in lateral recumbency. Depth of analgesia was assessed every 2-5 minutes by response to artery forceps applied to the digit and later at the skin proximal to the tarsal joint. In each case, the artery forceps was closed to the third ratchet. The onset of anesthesia, duration of analgesia, duration of recumbency, and recovery time were assessed. The onset of action was the time interval between the completion of drug administration and the bird becoming laterally recumbent. The duration of analgesia was the interval between the disappearance and reappearance of the pedal withdrawal reflex. The duration of recumbency was the interval between the onset of lateral recumbency and return to sternal posture with the head lifted. The recovery time was the interval between assumption of sternal posture and standing without ataxia. Each bird's heart rate, respiratory rate, and cloacal temperature were determined immediately after drug administration and at 10-minute intervals until the bird was sternal. Heart rates were recorded with the aid of a precordial stethoscope, and respiratory rates were counted by visual observation of abdominal wall excursions. Cloacal temperatures were measured in centigrade with a clinical thermometer. Observable adverse effects (eg, apnea, cyanosis, arrhythmia, diarrhea, regurgitation, and opisthotonus) were noted. Apnea was defined as breath-holding lasting >10 seconds, and cyanosis was defined as bluish discoloration of the tongue and/or ocular mucous membrane.

Data are presented as mean [+ or -] SD. Anesthetic indices were compared by using Student's paired t tests, whereas physiologic variables were compared by using analysis of variance for repeated measures. A P value of <.05 was accepted as significant in all cases.


Four of the anesthetized birds from group KX were easily aroused. One of the birds had watery diarrhea during the anesthetic period, and two others experienced profuse salivation. The only adverse reaction observed in the birds from group KXM was regurgitation (n = 2). Postrecovery excitement, characterized by wing flapping and circling, was observed in one bird from each group. All the birds had ruffled feathers during the course of anesthesia.

Anesthetic indices from both groups are shown in Table 1. The onset of anesthesia was longer in birds from group KX than in those from group KXM, but the difference was not statistically significant (P > .05). No appreciable analgesia was detected in group KX birds, whereas the duration of analgesia in group KXM birds was 37.4 [+ or -] 4.8 minutes. Similarly, the duration of recumbency was significantly higher in birds from group KXM compared with those from group KX (P < .05). However, the recovery time did not differ significantly between the groups (P > .05).

Changes in heart rate, respiratory rate, and cloacal temperature for both groups are shown in Figure 1. Heart rates did not differ significantly among the birds anesthetized with ketamine-xylazine and with ketamine-xylazine-midazolam (P > .05); however, the heart rates in both groups decreased progressively. Respiratory rates were significantly lower in birds anesthetized with ketamine-xylazine-midazolam compared with those anesthetized with ketamine-xylazine (P < .05). Cloacal temperatures were not significantly different between the birds in group KX and group KXM (P > .05); however, in each group, cloacal temperatures progressively decreased over time.


This is the first study that evaluated injectable anesthetics in guinea fowl and the first study that we are aware of assessing the effects of midazolam on the anesthetic indices and safety of ketamine-xylazine anesthesia in birds. In this study, we observed that intramuscular injection of 0.3 mg/ kg of midazolam improved the anesthetic quality of a ketamine-xylazine combination in guinea fowl without adversely affecting safety. Pain on intramuscular injection is partly the result of tension placed on the muscle fibers by the injectate but may also vary depending on the muscle used. (17) Greater reactions occur when injections are made into postural muscles or small muscles bound by inelastic fascia. (18) In most birds, intramuscular injections are best given in the pectoral muscles, but the thigh muscle is preferred in flightless birds because of the small pectoral muscle mass. (4) In this study, anesthetic was injected into the thigh muscles, because we thought it was necessary to divide the relatively large volume (0.55 ml/kg for ketamine-xylazine and 0.85 ml/kg for ketamine-xylazine-midazolam) between 2 sites. Pain with intramuscular injection was not observed in either group.

Two of the birds in the study experienced hypersalivation, and excessive salivation was reported with the use of ketamine in dogs, cats, ruminants, and vultures. (4) Although anticholinergics are routinely used in veterinary anesthesia for premedication, (6) their use in birds is controversial. These drugs are effective for the treatment of vagally induced bradycardia (19); however, they may increase the viscosity of secretions, which could plug narrow endotracheal tubes, especially in small birds. (20,21) For this reason, we did not pretreat the birds in this study with atropine or glycopyrrolate. However, with the possibility of hypersalivation when using this protocol in birds, intubation may be recommended to prevent aspiration.

Regurgitation and diarrhea were also observed in some birds anesthetized in this study. These adverse effects may also be associated with the use of xylazine. (22) Xylazine causes relaxation of the cardiac sphincter and reduction in the caudal esophageal sphincter pressure, thus resulting in reflux of gastric contents into the esophagus. As a result, most veterinary patients are fasted for several hours before premedication to reduce the volume of gastric content and decrease the risk of regurgitation or vomition. (6) Prolonged preoperative fasting may not be feasible in some avian species because of the risk of hypoglycemia. It is preferable to intubate birds immediately after induction of anesthesia to prevent aspiration of regurgitated materials.

All the birds in this study had ruffled feathers shortly after the induction of anesthesia. The cause of this reaction was unknown, although it was thought to be drug induced because it resolved spontaneously a few hours after recovery from anesthesia. The birds may have been mildly dehydrated, because food and water were withheld for 2 hours before anesthesia.

Study results showed that anesthesia induced by intramuscular injection of ketamine and xylazine alone does not produce appreciable analgesia in guinea fowl. This finding was similar to those from earlier studies in other avian species. (7,23) However, anesthesia induced by a ketamine, xylazine, and midazolam combination in guinea fowls was characterized by analgesia that lasted 37.4 [+ or -] 4.8 minutes. A similar study in pigs suggested that midazolam may be additive to a ketamine-xylazine combination at both the hypnotic and analgesic end points. (24) The findings in our study may be the result of deeper hypnosis occasioned by administration of midazolam, because the drug is not known to have analgesic effects. The longer duration of recumbency in group KXM of anesthetized guinea fowl may not be acceptable in clinical settings, because this would require additional patient monitoring. However, this effect may be reversed with the use of flumazenil. (2)


Although body temperatures are not routinely monitored as closely in avian species as in other veterinary patients, such evaluation is essential during anesthetic procedures. Low body temperatures can result in delayed recovery, likely because of metabolic enzyme inactivation. In this study, we monitored the cloacal temperature until the birds recovered, and, in both groups, the cloacal temperature decreased progressively. This may be associated with the depressant effect of xylazine on the hypothalamus as well as muscle relaxation.

The greatest concern with the use of an alpha-adrenergic agonist such as xylazine is the severe cardiopulmonary depressant effects. Xylazine was reported to reduce both the heart rate and cardiac output in dogs. (19) In addition, the arrhythmogenic effects of an alpha-adrenergic agonist can result in cardiovascular instability. (4) In this study, there was no significant difference in the heart rate between group KX and group KXM of the anesthetized guinea fowl, although there was a progressive decrease in the heart rates among birds in both groups. Although one might have expected the decreases in heart rates to be more pronounced because the birds were not pretreated with atropine, the sympathomimetic action of ketamine may have had a protective effect.(5,6) This supports the use of a ketamine-xylazine combination instead of the use of xylazine alone.

The respiratory effects of combined ketamine-xylazine anesthesia were reported in birds. (12) In mallard ducks, the combination was associated with cyanosis and apnea, which resulted in the death of 2 ducks. (2) The respiratory depression was attributed to the use of xylazine. In this study, we observed that midazolam significantly added to the respiratory depression observed with the ketamine-xylazine combination. This finding may be attributable to the deeper hypnosis occasioned by the additive effect of midazolam on this anesthetic combination. However, contrary to the findings in ducks, neither cyanosis nor apnea was observed in the guinea fowl. Regardless, supplemental oxygen might be beneficial for birds being anesthetized with ketamine-xylazine. Because of the decrease in respiratory rate and the possible risk of regurgitation with midazolam, proper monitoring and endotracheal intubation of the patient is recommended.


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R. Adetola Ajadi, DVM, MVSC, Olajide B. Kasali, DVM, PhD, Dipl ACVP, A. Folashade Makinde, DVM, Adenike I. Adeleye, DVM, J. A. Oyewusi, DVM, MSc, and Olukayode G. Akintunde, DVM, MSc

From the College of Veterinary Medicine, University of Agriculture, PMB 2240, Alabata Rd, Abeokuta, Nigeria.

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Table 1. Comparison of anesthetic indices in guinea fowl (n = 20)
after administration of ketamine-xylazine or

                              Group KX,           Group KXM,
Anesthetic indices          min (n = 10)         min (n = 10)

Onset of anesthesia        3.2 [+ or -] 1.3    1.3 [+ or -] 0.15
Duration of analgesia             0           37.4 [+ or -] 4.8 *
Duration of recumbency    56.4 [+ or -] 5.4   91.4 [+ or -] 7.6 *
Recovery time             26.3 [+ or -] 8.9   18.6 [+ or -] 5.6

Abbreviations: K indicates ketamine, 15 mg/kg IM; X, xylazine,
2.5 mg/kg IM; M, midazolam, 0.3 mg/kg IM.

* P < .05.
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Title Annotation:Original Studies
Author:Ajadi, R. Adetola; Kasali, Olajide B.; Makinde, A. Folashade; Adeleye, Adenike I.; Oyewusi, J.A.; Ak
Publication:Journal of Avian Medicine and Surgery
Article Type:Report
Geographic Code:1USA
Date:Sep 1, 2009
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