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EVALUATION OF DRUG COMBINATIONS IN TOTAL INTRAVENOUS ANAESTHESIA IN WEST AFRICAN DWARF GOAT
ABSTRACT
The physiological, biochemical and anaesthetic effects of the drug combinations were studies in West African Dwarf goat. In protocol I, there was a significant (p < 0.05) increase in the HR of GP I goats at 10 mins post-induction (PI), which significantly (p < 0.05) decreased from 30 min PI. The HR significantly decreased (p < 0.05) at 20 min in GP IV goats, and at 10 min GP II goats, and returned to the pre-anaesthetic value at 40 min PI. However, HR decreased significantly (p < 0.05) between 10 – 50 mins PI in GP A and B and between 40-80 min PI in GP D. The RR decreased significantly (p < 0.05) at 10 and 20 mins PI in GPs A and B respectively, till 40 min PI and at 30 mins PI in GP D. These changes normalized at 40 min PI when compared to the pre-anaesthetic values in protocol I. The RR decreased significantly (p < 0.05) between 10 – 80 mins, 10 – 50 mins, 30 – 80 mins PI in GPs A, B, and D respectively, but significantly increased at 20 min PI in GP C. The RT of the goats dropped significantly (p < 0.05) between 10 – 40 mins PI in GP I and GP II. However, there was significant (p < 0.05) decrease in RT between 20 – 30 mins and 10 – 30 mins PI in GPs A, and B respectively. The induction was good and smooth in GPs II, IV, B and D, slightly excitment in GPs I, III, A and C. The quality of recovery was fair in GPs I and A, good in GPs II and III, B and C, good and rapid in GP IV and D. Side effects such as salivation, coughing, ataxia, apnoe, snoring and phonation were observed in both protocols. There was significant (p < 0.05) decrease in PCV at 30 min PI in GPs I, III, IV and D. The mean HB decreased significantly (p < 0.05) at 30 min PI in GPs III, IV and A, and at 1440 min PR in GP II, while the values increased significantly (p < 0.05) at 120 min PR in GP A. Significant (p < 0.05) decrease in RBC was recorded in GP II at 30 min PI, and between 120 -1440 min PR. The mean pre-anaesthetic blood glucose levels (BGL) were 75.00 ± 1.29, 68.50 ± 2.84, 48.50 ± 3.23, and 53.50 ± 4.69 mg/dl for GPs I, II, III and IV, respectively. These values significantly (p < 0.05) increased at 30 mins PI in all the GPs and returned to pre-anaesthetic value at 120 min post-recovery (PR) in GPs I and IV, decreased significantly (p < 0.05) from 120 -1440 min PR in GP II. The BGL values increased significantly (p < 0.05) at 30 min PI in GPs A, B C and D. It remained consistent at 120 min PR in GPs B, C and D and returned to base line value in all these GPs at1440 min PR. The cortisol level significantly (p < 0.05) decreased at 30 min PI in GP II but increased significantly (p < 0.05) at 120 min PR in GPs I, II, III and IV compared to pre-anaesthetic values. There was a significant decrease (p < 0.05) in the cortisol level at 30 min PI in GP B only and increased significantly (p < 0.05) at 102 min PR in GPs A, C, and D, and at 1440 min in GP B.
It was concluded that the anaesthetic drug combinations resulted in the smooth and uneventful induction with mild cardiopulmonary depressions and rapid recovery. Their effects on haematological values as well as biochemical values were also mild. The xylazine + ketamine + propofol, xylazine + ketamine and xylazine + propofol combinations produced sufficient surgical anaesthetic durations both in single injection and maintenance procedures and may be used successfully in both short and long surgical procedure without an incident of untoward side effects. The ketamine + propofol combination produced greater haemodynamic stability than other combinations but with shortest duration of surgical anaesthesia.
Therefore, the use of the drug combinations is promising especially in good quality anesthesia, rapid onset and rapid recovery
TABLE OF CONTENTS
Title page – – – – – – – – – – – i
Certification – – – – – – – – – – – ii
Dedication – – – – – – – – – – – iii
Acknowledgements – – – – – – – – – – iv
Table of contents – – – – – – – – – – v
List of figures – – – – – – – – – – xv
List of tables – – – – – – – – – xvii
Abstract – – – – – – – – – – – xix
CHAPTER ONE: INTRODUCTION – – – – – – – 1
1.1 Objective of the study – – – – – – 3
1.1.1 Specific objectives of the study – – – – – 3
1.2 Justification of the study – – – – – – 4
1.3 Null Hypotheses – – – – – – – 4
CHAPTER TWO: LITERATURE REVIEW – – – – – – 5
2.1 Intravenous anaesthesia – – – – – – – 5
2.2 Propofol – – – – – – – – – 7
2.2.1 Chemical properties of Propofol- – – – – – 7
2.2.2 Pharmacokinetic and pharmacodynamic properties – – – 8
2.2.3 Effects on organ systems – – – – – – 10
2.2.3.1 Central nervous system – – – – – – – 10
2.2.3.2 Cardiovascular system – – – – – – 12
2.2.3.3 Respiratory system – – – – – – – 15
2.2.4 Other properties – – – – – – – 15
2.2.5 Uses, Anaesthesia and Analgesia – – – – – 16
2.2.6 Side effects – – – – – – – 17
2.3 Ketamine – – – – – – – 17
2.3.1 Chemical properties – – – – – – – 18
2.3.2 Pharmacokinetic and pharmacodynamic proerties – – – 19
2.3.3 Effects on organ systems – – – – – – 20
2.3.3.1 Central nervous system – – – – – – – 20
2.3.3.2 Cardiovascular system – – – – – – – 22
2.3.3.3 Respiratory system – – – – – – – – 23
2.3.4 Other effects – – – – – – – – 24
2.3.5 Uses, Anaesthesia and Analgesia – – – – – – 25
2.3.6 Side effects – – – – – – – – 26
2.4 Xylazine – – – – – – – – 26
2.4.1 Chemical properties – – – – – – – 27
2.4.2 Pharmacodynamic and pharmacokinetic properties – – – 27
2.4.3 Effects on organ system – – – – – – 28
2.4.3.1 Central nervous system – – – – – – 28
2.4.3.2 Cardiovascular system – – – – – – 29
2.4.3.3 Respiratory system – – – – – – – 30
2.4.3.4 Effect on temperature – – – – – – – 31
2.4.4 Other effects – – – – – – – – 32
2.4.5 Uses, Anaesthesia, Analgesia and sedation – – – – 32
2.4.6 Side effects – – – – – – – – – 34
2.5 Haematology and biochemistry – – – – – – 34
2.5.1 Packed Cell Volume (PCV) – – – – – – 35
2.5.2 Haemoglobin (Hb) concentration- – – – – – 36
2.5.3 Red Blood Cells (RBC) – – – – – – 36
2.5.4 Total White Blood Cells – – – – – – 37
2.5.5 Blood glucose- – – – – – – – 38
2.5.6 Serum Cortisol- – – – – – – – 39
2.5.7 Blood Urea Nitrogen (BUN) – – – – – – 42
2.5.8 Serum Creatinine- – – – – – – – 43
2.5.9 Alanine Aminotransferase (ALT) – – – – – – 44
CHAPTER THREE: MATERIALS AND METHODS – – – – 45
3.1 Preparation of animal house – – – – – – 45
3.2 Animals and their management- – – – – – 45
3.3 Anaesthetic drugs/ agents- – – – – – – 46
3.4 Pilot study: Establishment of Propofol dosage in WAD goats- – 46
3.4.1 Animals- – – – – – – – – 46
3.4.2 Drug administration- – – – – – – – 46
3.5 Experimental procedure – – – – – – – 47
3.5.1 Animals- – – – – – – – – 47
3.5.2 Drug administration – – – – – – – 47
3.5.3 Protocol I – – – – – – – – 47
3.5.4 Protocol II – – – – – – – – 48
3.6 Parameters monitored – – – – – – – 49
3.6.1 Heart Rate – – – – – – – – 49
3.6.2 Respiratory Rate – – – – – – – 49
3.6.3 Rectal Temperature – – – – – – – 49
3.7 Determination of Quality of Anaesthesia – – – – 50
3.7.1 Onset of Analgesia – – – – – – – 50
3.7.2 Duration of Analgesia – – – – – – – 50
3.7.3 Duration of recumbency – – – – – – 50
3.7.4 Standing time – – – – – – – – 51
3.7.5 Quality of induction and recovery – – – – – 51
3.7.5.1 Induction quality scoring – – – – – – 51
3.7.5.2 Recovery quality scoring- – – – – – 51
3.7.6 Side effects – – – – – – – – – – 52
3.8 Haematology and Biochemistry- – – – – – 52
3.8.1 Blood sample collection- – – – – – – 52
3.8.2 Packed Cell Volume (PCV) – – – – – – 52
3.8.3 Haemoglobin (Hb) concentration- – – – – – 53
3.8.4 Red Blood Cell (RBC) counts- – – – – – 53
3.8.5 Total White Blood Cell counts- – – – – – 54
3.8.6 Blood glucose level- – – – – – – 54
3.8.7 Serum Cortisol level- – – – – – – – 55
3.8.7.1 Procedure for Serum Cortisol ELISA Assay – – – – 55
3.8.8 Serum Urea Nitrogen – – – – – – – 56
3.8.8.1 Procedure for determination of Serum Urea Nitrogen – – 56
3.8.9 Serum Creatinine level – – – – – – 57
3.8.9.1 Procedure for determination of Serum Creatinine level – – 57
3.8.10 Serum Alanine Aminotransferase (ALT) – – – – 58
3.8.10.1 Procedure for determination of Serum Alanine Aminotransferase (ALT) 59
3.8.11 Data Analysis – – – – – – – – – 59
CHAPTER FOUR: RESULTS – – – – – – – – 60
4.1 Pilot study – – – – – – – – 60
4.1.1 Physiological variables- – – – – – – 60
4.1.1.1 Heart Rate- – – – – – – – – 60
4.1.1.2 Respiratory rate- – – – – – – – 60
4.1.1.3 Rectal temperature – – – – – – – 60
4.1.2 Anaesthetic indices – – – – – – – 64
4.1.2.1 Onset of analgesia – – – – – – – 64
4.1.2.2 Surgical anaesthetic time – – – – – – 64
4.1.2.3 Recumbent time – – – – – – – 64
4.1.2.4 Standing time – – – – – – – – 64
4.2 Protocol I – – – – – – – – 69
4.2.1 Physiological variables- – – – – – – 69
4.2.1.1 Heart rate – – – – – – – – 69
4.2.1.2 Respiratory rate – – – – – – – 69
4.2.1.3 Rectal temperature – – – – – – – 72
4.2.2 Anaesthetic indices – – – – – – – 74
4.2.2.1 Onset of analgesia – – – – – – – 74
4.2.2.2 Surgical anaesthetic time – – – – – – 74
4.2.2.3 Recumbent time – – – – – – – 74
4.2.2.4 Standing time – – – – – – – – 74
4.2.2.5 Quality of induction and recovery- – – – – – 79
4.2.3 Side effects – – – – – – – – 79
4.2.4 Haematological and biochemical values- – – – – 82
4.2.4.1 Packed Cell Volume (PCV) – – – – – – 82
4.2.4.2 Haemoglobin (Hb) concentration- – – – – – 82
4.2.4.3 Red Blood Cell (RBC) counts- – – – – – 82
4.2.4.4 Total White Blood Cell counts- – – – – – 86
4.2.4.5 Blood glucose level- – – – – – – 86
4.2.4.6 Serum Cortisol level- – – – – – – – 86
4.2.4.7 Urea Nitrogen- – – – – – – – 90
4.2.4.8 Serum Creatinine level – – – – – – 90
4.2.4.9 Serum Alanine Aminotransferase (ALT) – – – – 90
4.3 Protocol II – – – – – – – – 94
4.3.1 Physiological variables- – – – – – – 94
4.3.1.1 Heart rate – – – – – – – – 94
4.3.1.2 Respiratory rate – – – – – – – 94
4.3.1.3 Rectal temperature – – – – – – – 94
4.3.2 Anaesthetic indices – – – – – – – 98
4.3.2.1 Onset of analgesia – – – – – – – 98
4.3.2.2 Surgical anaesthetic time – – – – – – 98
4.3.2.3 Recumbent time – – – – – – – 98
4.3.2.4 Standing time – – – – – – – – 98
4.3.2.5 Nature of induction and recovery- – – – – – 103
4.3.2.6 Side effects – – – – – – – – 103
4.3.3 Haematological and biochemical values- – – – – 106
4.3.3.1 Packed Cell Volume (PCV) – – – – – – 106
4.3.3.2 Haemoglobin (Hb) concentration- – – – – – 106
4.3.3.3 Red Blood Cell (RBC) counts- – – – – – 106
4.3.3.4 Total White Blood Cell counts- – – – – – 106
4.3.3.5 Blood glucose level- – – – – – – 111
4.3.3.6 Serum Cortisol level- – – – – – – – 111
4.3.3.7 Urea Nitrogen- – – – – – – – 111
4.3.3.8 Serum Creatinine level – – – – – – 111
4.3.3.9 Serum Alanine Aminotransferase (SALT) – – – – 116
CHAPTER FIVE: DISCUSSION AND CONCLUSION – – – – 118
5.1 Discussion – – – – – – – – – 118
5.2 Conclusion – – – – – – – – – 125
REFERENCES – – – – – – – – – 127
APPENDIX – – – – – – – – – 145
CHAPTER ONE
1.0 INTRODUCTION
Goats are essential domestic animals in Nigeria and beyond. Many households’ rear goats and majority of them practice traditional free-range system. The free-range system often predisposes sheep and goat to injuries like fractures and matchet cut (Eze and Nlebedum, 2007). Some of the injuries need urgent and immediate surgical treatment. Most of the surgical cases, (Eze and Idowu, 2002), in major veterinary hospitals and state clinic in Nigeria (arising from dystocia, castration, fracture and sadism), ranks third among cases reported.
In any surgical case, good choice of anaesthetics especially in ruminant cannot be over emphasized. The practice of combining two or more drugs is common and has become a technique to achieve a balanced anaesthesia. The purpose of a balanced anesthetic technique is to achieve all of the components of general anesthesia while minimizing the negative aspects of individual drugs on cardiopulmonary function (Mama, 2000). It is quite obvious that continuous search for proper drug combination that will offer good quality anaesthesia, analgesia and fast recovery with mild or no side effect is ongoing.
Propofol (2, 6-diisopropylphenol) is a phenolic compound unrelated to any other general anesthetics. It is a non-barbiturate, non dissociative and non cumulative intravenous anesthetic agent (Hall et al., 2001). It has good quality anesthesia, rapid onset and short duration of action, with rapid recoveries making the drug potentially useful in ruminants, in which these features are particularly desirable (Nikitas et al., 2005). Hall et al., (2001) stated that propofol has been accepted as most useful anesthetic agent in all domestic animals but its use in large animals is hampered by the cost. It is used alone and in combination with other drugs in dogs, cat, cattle, horse, ponies and goats (Lin et al., 1997; Mama, 2000; Lerch et al., 2000; Hall et al., 2001, and Steffey et al., 2009.). Reports on the use of propofol for induction and maintenance of anaesthesia have indicated its suitability in goats (Hall et al., 2001; Prassinos et al., 2005, and Khan 2006). Propofol has been shown to be compatible with wide range of drugs used for premedication, inhalation anesthesia and neuromuscular block (Hall et al., 2001). Since it has little or no analgesic property, it is recommended to combine propofol with an analgesic agent (opoid or alpha-2-adenoreceptor agonist) for painful procedure.
Xylazine is an alpha-2-adenoreceptor agonist, is non opoid group with analgesic, sedative and muscle relaxant effects and is used commonly in veterinary practice (Fereidoon et al., 2005). Xylazine is a commonly used sedative in ruminants but there are concerns about the threat of hypoxaemia associated with its use in small ruminants (Dzikit et al., 2009). It has been used in combination with propofol in sheeps (Khan 2006) and with ketamine in intravenous general anaesthsia in goat. (Udegbunam and Adetunji, 2007). Ketamine is a dissociative anaesthetic agent which is licensed for use in dogs intravenously. It produces stable haemodynamics during anaesthesia as a result of its stimulatory effect on the sympathetic nervous system, which counteracts the depressant effects of other drugs used during anaesthesia (Lerch et al., 2000). It produces profound analgesia without muscle relaxation and tonic-clonic spasms of limbic muscles may occur even in the absence of surgical or other stimulation (Hall et al., 2001). However, it can be used for anesthesia in sheep and goat without the fear of causing convulsion (Fereidoon et al., 2005),
According to Mayer et al., (1990), ketamine causes an increase in mean arterial pressure (MAP) and cardiac index (CI) while propofol an intravenous hypnotic, in contrast, produces a reduction in both mean arterial pressure (MAP) and cardiac index (C I) . Ketamine and propofol appear to counter each other’s adverse effects, conferring several advantages including haemodynamic stability (Rapeport et al., 2009). Ketamine-propofol combination allows a reduction in the hypnotic dose of propofol and a decrease in the cardiovascular depression induced by this drug (Tatiana et al., 2008). According to Lerche et al., (2000) the major side effects of propofol (reduced haemodynamics during induction) and ketamine (psychic disturbances and cardiovascular stimulation) were absent and respiratory function post-surgery was adequate in ketamine-propofol anaesthesia. Ketamine-propofol offer haemodynamic stability while ketamine-xylazine produces long surgical anaesthetic duration (Udegbunam and Adetunji, 2007). It will thus be useful to study the combination of the three drugs to explore their synergistic effect expecting haemodynamic stability, longer surgical anaesthetic time and fast, smooth recovery.
1.1. OBJECTIVE OF THE STUDY.
To evaluate the physiological effect and anaesthetic properties of propofol and its drug combinations in West African Dwarf goat.
1.1.1. SPECIFIC OBJECTIVES OF THE STUDY;
This study was therefore designed with the following specific objectives;
To compare the effect of the total intravenous administration of different drug combination of propofol, xylazine, ketamine on heart rate, respiratory rate, rectal temperature, blood cell count and serum biochemistry in WAD goat.
To study the nature of induction, indices of anesthesia, and the quality of recovery following the administration of these drug combinations.
To observe any incidence of side effects associated with the use of these drug combinations.
1.2. JUSTIFICATION OF THE STUDY
This study would help achieve the objective of total intravenous anesthesia (TIVA)
without the use of inhalation anesthetic agents.
Information generated from this study would be of immense importance to some
veterinary hospitals and clinics that have no functional anesthetic machines and good post
operative monitoring protocol.
This study was designed to achieve reduction in dosage of the individual agents in the
combination thereby reducing side effects.
1.3. NULL HYPOTHESES
Different drug combination of propofol, ketamine and xylazine has no different effect on
vital parameters – heart rate, respiratory rate and rectal temperature.
There is no observable effect on the blood count and serum biochemistry as a result of
administration of the different drug combination.
The different drug combinations of propofol, xylazine and ketamine offer no synergistic
effect.
There is no side effect associated with the use of these drug combinations.
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