Medycyna Wet. 2009, 65 (1) 29
Praca oryginalna Original paper
A vital principle of safe anaesthesia is a proper choice of the anaesthetic agent, subject to the patients physical condition and the surgical intervention sche-duled. A common general anaesthesia method that enables long-lasting surgical procedures with a low anaesthetic risk is general inhalation anaesthesia. In-halation anaesthesia requires the administration of pre-medication agents as well as the use of anaesthesia--inducing preparations (18). These drugs may cause de-pression in the cardiovascular and respiratory systems and thus their activity adds significantly to the anaesthetic risk. Agents used for premedication and the induction of inhalation anaesthesia may deepen the pre-existing medical conditions and evoke various responses in the animals undergoing a surgical procedure. Therefore, proper anaesthetics should be selected to ensure the lowest risk of disturbances, especially the respiratory depression, and to minimise potential anaesthetic com-plications.
A new premedication agent in widespread current use is midazolam (8-choro-6-(2-fluorophenyl-1
methyl)--4H-imidazo-benzodiazepine). Midazolam at clinical doses has a minimal depressive effect on the cardio-vascular system and gas exchange. In the case of fast intravenous administration, it may produce a deeper depression of the respiratory system than diazepam (32). Midazolam as a single agent appears to have a mild sedative effect on dogs, yet it shows synergistic activity when administered in association with other drugs of this type (8).
A medicament used for general anaesthesia and in-halation anaesthesia induction is propofol (2-6 disopro-pylphenol). This drug is a short-acting anaesthetic agent (22, 26, 31). Propofol administered as monoanaesthe-tic does not decrease the heart rate at the concurrent hypotension recorded (4). In dogs, the drug impairs the myocardial contractility (20), while producing the arte-rial and venous vasodilatation it causes transient hypo-tension (5, 7, 27). The changes occurring in the respira-tory system output under propofol administration are also associated with the premedication agent used and its dose. Its application produced acute respiratory
Propofol-induced inhalation anaesthesia in dogs
after xylasine or xylasine and midazolam premedication
ANDRZEJ ÆWIEK*, IRENEUSZ BALICKI, DOROTA RÓ¯AÑSKA, IZABELA POLKOWSKA, MACIEJ ORZELSKI
*Gilmore Veterinary Practice, 52-54 High Street Standish, Wigan, England
Department and Clinic of Animal Surgery, Faculty of Veterinary Medicine, University of Life Sciences, G³êboka 30, 20-612 Lublin, Poland
Æwiek A., Balicki I., Ró¿añska D., Polkowska I., Orzelski M.
Propofol-induced inhalation anaesthesia in dogs after xylasine or xylasine and midazolam premedication
Summary
The objective of the studies was to compare the premedication with xylasine alone and a midazolam/xylasine combination applied for inhalation anaesthesia induction with propofol. The studies aimed at determining the effect of the examined anaesthesia methods on the animals physical condition, the acid-base balance parameters and arterial blood oxygenation. The study was conducted on 48 male mixed-breed dogs aged from 3 to 11 years, of 5-25 kg body weight. The animals were divided into two groups. Group I was premedicated with xylasine (2 mg/kg bw.) and atropine (0.05 mg/kg bw.) intramuscularly, and group II was administered xylasine (1 mg/kg bw.), atropine (0.05 mg/kg bw.) and midazolam (0.2 mg/kg bw.) intramuscularly. In both groups the premedication was followed after 20 minutes with propofol used for induction, given to effect intravenously. General anaesthesia was conducted by administering a mixture of halothane and oxygen. Propofol was shown to induce loss of consciousness in the animals premedicated with xylasine alone or a xylasine/ midazolam combination at the mean dose of 3.12 and 3.13 mg/kg bw. respectively. Premedication with single-agent xylasine or xylasine in a twofold lower dose in conjunction with midazolam does not affect the propofol dose required to induce unconsciousness. The administration of midazolam/xylasine preanaesthetics compared to the premedication with xylasine alone suppresses vomiting as well as accelerates the recovery and return of motor functions in patients anaesthetised with propofol.
Medycyna Wet. 2009, 65 (1) 30
acidosis and decreased arterial blood oxygenation. Be-sides, it caused a short-term rise of pulmonary shunt (10). The objective of the current study was to investigate premedication with midazolam and xylasine for the induction of inhalant anaesthesia with propofol, and to compare this procedure to monoanaesthetic xylasine premedication as well as to determine the influence of each anaesthetic method on the general physical status of the anaesthetised animals, the acid-base balance parameters and arterial blood oxygenation.
Material and methods
The study included 48 male mixed-breed dogs, aged from 3 to 11 years, of 5-25 kg body weight. The dogs were the patients of the Department and Clinic of Animal Surgery, Agricultural University in Lublin where they were put under general anaesthesia to undergo a desexing surgery. The in-vestigated animals were clinically normal. They were fasted for 24 hrs prior to the anaesthesia induction. The dogs were divided into two groups 24 animals each.
Group I: the dogs were premedicated with 2 mg/kg bw. of xylasine (Rometar, Spofa, Czech Republic) and 0.05 mg/kg bw. of atropine (Atropinum sulfuricum,WZF Polfa, Poland), intramuscularly, followed after 20 minutes by propofol (Plofed WZF Polfa, Poland) used for induction, given to effect intravenously. General anaesthesia was conducted by administering a mixture of halothane and oxygen.
Group II: the dogs were premedicated with 1 mg/kg bw. of xylasine (Rometar, Spofa, Czech Republic), 0.05 mg/kg bw. of atropine (Atropinum sulfuricum,WZF Polfa, Poland) and 0.2 mg/kg bw. of midazolam (Midanium, WZF Polfa, Poland), intramuscularly, followed after 20 minutes by propofol (Plofed WZF Polfa, Poland) used for induction, given to effect intravenously. General anaesthesia was conducted by administering a mixture of halothane and oxygen.
The dose of the intravenous propofol infusion depended on the observed anaesthetic effect (loss of eyelid and corneal reflexes, pain sensation and withdrawal reflex). The introduc-tion of the cuffed endotracheal tube was followed by the in-halation anaesthesia induction with a halothane and oxygen mixture. Halothane was administered for approximately 5 mi-nutes at 3.5% concentration and for another 10 mi5 mi-nutes at 1.5% concentration with the oxygen supply of about 0.5 l/ min. The inhalant anaesthesia proceeded in the closed-circuit anaesthetic machine. The surgical intervention lasted for ap-proximately 15 minutes and after this period the halothane flow was stopped. Over the following 15 minutes only oxygen was administered and afterwards the anaesthetic machine was disconnected. Patients were extubated immediately after the first reflexes occurred.
The level of anaesthesia induced by the above agents was assessed by observing palpebral, corneal and withdrawal reflexes as well as superficial sensitivity and the animals response to the ligation of spermatic cords.
The general physical condition of the dogs was monitored by recording the heart rate (cardiomonitor S & W), respira-tory rate and rectal body temperature. These parameters were measured before the anaesthetic agent administration as well as in the 15th, 25th and 40th minute after the beginning of
anaesthesia; the last measurement was taken in the 60th minute,
that is about 20 minutes after the cessation of halothane administration.
In 30 dogs (15 animals in each group), arterial blood gaso-metry parameters were examined. The following acid-base balance parameters were determined: pH, present content of bicarbonates (HCO3), standard base excess (SBE), carbon
dioxide partial pressure (PaCO2) as well as the arterial oxygen
parameters: oxygen partial pressure (PaO2) and arterial oxy-genation (SatO2). Blood samples for the gasometry analyses were collected from the femoral artery. The determinations were made prior to the premedication and in the 25th minute
of anaesthesia five minutes after the induction of anaesthe-sia and in the 40th minute of that procedure just before the
cessation of halothane flow and in the 60th minute of
ana-esthesia. The examination of acid-base balance parameters and arterial blood oxygenation was performed by means of the Corning 238 apparatus with computer-aided software.
The values of the investigated parameters were analysed statistically to determine the arithmetic mean and standard deviation (± SEM). To define the relationship between the drug dose and the patients age and body weight, the Pearson correlation coefficient and Students t-test were employed to examine its significance for p < 0.05 and p < 0.01. To establish the statistically significant differences between the body temperature, heart rate, respiratory rate in the 0 and 15th,
25th, 40th, 60th minute and significant differences between the
parameters of acid-base balance and blood oxygenation between the 0 and 25th, 40th and 60th minute, the Wilcoxon
signed-rank test for the related data was applied. This test is an alternative to the paired Students t-test when it is impos-sible to state if the distribution of the ranks tends towards the normal distribution.
Results and discussion
Over the period of 10-15 minutes following the premedication, the animals showed sedative symptoms they maintained a recumbent position and exhibited a reduced response to external stimuli. The sedation depth was comparable in all treated groups. In group I, vomiting was recorded in 30% of patients, whereas in group II in 15%. Mean doses of propofol administered for induction were 3.13 mg/kg bw. ± 0.76 in group I and 3.12 mg/kg bw. ± 0.67 in group II.
Correlation coefficients between the drug dose and dogs body weight or age are presented in tab. 1. The data indicated that in group I there was no statistically significant correlation between the age or body weight and the propofol dose. In group II, however, the cor-relation between the dose of the drug used for induc-tion and the patients age proved to be statistically significant.
Propofol administration in group I and II produced the apnoea period persisting for 20-40 seconds. Through-out the 15 minutes anaesthesia with halothane/oxygen
r e t e m a r a P GroupI Group II e g A 0.24 0.56* t h g i e w y d o B -0.20 0.16* -Explanation: * p < 0.05
Tab. 1. Correlation coefficients between animals age or body weight and propofol dose in group I and II
Medycyna Wet. 2009, 65 (1) 31
mixture all the patients showed the loss of palpebral, corneal and superficial sensitivity as well as limb with-drawal reflexes and the reflexes from the operation field. After ceasing the halothane administration the animals regained their ability of response to external stimuli after 10 minutes in group I and after 7 minutes in group II. The recovery of motor functions manifested by attempts to stand up occurred
22 minutes after the completion of anaes-thesia in group I and after 16 minutes in group II.
The parameters of general condition, acid-base balance and blood oxygenation are presented in tab. 2-5.
Administering pro-pofol and midazolam combinations seems to be a very attractive anaesthetic method,
therefore it has been the object of exten-sive studies (3, 14, 15, 19, 25, 28). Since xylasine-induced vomiting is fre-quently reported, it should be empha-sised that in dogs premedicated with xylasine/midazolam the vomiting rate is decreased by 50% as compared to those administered xylasine alone. The present studies showed that the mean doses of propofol required after xylasine medication and xylasine/midazolam pre-medication were the same. Midazolam premedication reduced xylasine doses, yet it did not lower the propofol dose required for induction. Similar results were obtained by Kuusela et al. (11) who stated that the propofol dose required for inducing general anaesthesia does not depend on the type of the drug used for premedication but on its dose. A higher dose of premedicative agents reduced the required dose of propofol. In the present research, the amount of propofol admi-nistered in both groups appears to be low as compared to that mentioned in other research papers. Adetunji et al. (2), pre-medicated dogs with xylasine and then
administered propofol at the dose of 5 mg/kg bw. Alike, Watkins et al. (31), and Morgan and Legge (16) recommended propofol doses ranging from 5.9 up to 6.5 mg/kg bw. The drug was also used at the dose of 2 mg/kg bw. (6, 12). According to the present studies, in both groups no relationship between the patients body weight and the overall mean propofol dose was recor-ded. However, a relationship between the mean dose of
propofol and patients age was observed and it was more pronounced in older dogs.
Premedication with xylasine lowered the heart rate. The depressive effect of xylasine on heart contraction frequency was often reported by other authors (9, 23, 24, 29, 30). The present research revealed a reduced cardiac rate under xylasine in group I, while no such effect was recorded in group II including animals
pre-r e t e m a r a P Group Examinaiton itmeinminutes ' 0 15' 25' 40' 60' y d o B e r u t a r e p m e t (° )C I 38.53±0.40 39.30±0.48** 39.02±0.62 38.84±0.64 38.40±0.73** II 38.65±0.61 39.35±0.65** 38.88±0.71 38.38±0.83 37.82±1.02** e t a r tr a e H ) n i m /f ( I 116.62±27.12 189.15±48.55 120.31±51.62 111.62±30.95 104.85±28.53* II 115.20±23.91 116.90±60.09 137.70±32.24 107.50±17.47 194.40±17.48* e t a r y r o t a ri p s e R ) n i m /f ( I 29.92±11.46 17.08±6.93** 16.08±9.18** 16.23±13.63* 17.08±10.63* II 27.00±6.72 14.70±6.88** 12.70±8.60** 15.40±5.97** 27.90±17.30*
Tab. 3. Results of body temperature, heart and respiratory rate measurements (x ± s)
Explanations: * p £ 0,05; ** p £ 0,01 statistical significance between time 0 and next measurement (15, 25, 40, 60 minutes) r e t e m a r a P GroupI Group II l a n r e t x e f o n r u t e R s s e n e v i s n o p s e r il u m it s 10.20±1.28 17.16±1.04 n o it c n u f r o t o m f o n r u t e R 22.25±2.19 16.16±3.04
Tab. 2. Recovery time of external stimuli responsiveness and motor function return after anaesthesia completion in group I and II (time in minutes)
r e t e m a r a P Group Examinaiton itmeinminutes ' 0 25' 40' 60' H p ) g o l-( I 7.35±0.02 7.28±0.03** 7.27±0.02** 7.33±0.02 II 7.36±0.02 7.30±0.04** 7.30±0.04** 7.35±0.05 O C a P 2 ) a P K ( I 30.88±1.81 41.38±7.69** 42.88±3.40** 35.38±3.07** II 31.50±3.17 43.30±3.97** 42.80±5.31** 38.30±3.53** O C H 3 )l /l o m m ( I 19.41±1.19 19.91±1.76 20.24±1.54 20.39±1.56* II 20.12±1.25 20.54±1.25 20.64±1.12 21.21±1.36*
Tab. 4. Results of acid-base balance parameters analysis (x ± s)
Explanations: as in tab. 3 r e t e m a r a P Group Examinaiton itmeinminutes ' 0 25' 40' 60' O a P 2 ) a P k ( I 97.25±6.54 82.63±42.45** 252.25±36.30** 83.88±10.62* II 98.60±9.59 71.60±13.82** 214.40±55.42** 86.90±9.17* O t a S 2 ) % ( I 97.04±0.79 86.34±10.10* 99.53±0.50* 94.13±4.16** II 97.03±0.80 88.02±8.86** 98.80±2.54* 95.34±2.18** E B S )l /l o m m ( I 7.15±1.56 5.88±2.96** 4.95±1.95** 5.54±2.51** II 6.23±2.10 4.74±1.66** 4.30±1.52** 4.15±1.62** Explanations: as in tab. 3
Tab. 5. Results of arterial blood oxygenation and standard base excess analysis (x ± s)
Medycyna Wet. 2009, 65 (1) 32
medicated with xylasine and midazolam. The unchan-ging heart contraction frequency is probably the effect of midazolam. At anaesthesia induced with midazolam and propofol, a rising heart rate was observed. This rise should be definitely attributed to midazolam affecting the heart rate decreased previously by xylasine.
Propofol-induced general anaesthesia followed by halothane administration caused apnoea and a persisting lowered respiratory rate. It may be concluded that only in the patients sedated with xylasine and propofol, halothane was shown to have a substantial influence on the respiratory rate. The studies by Wasak (30) indica-ted that a return to a normal respiratory rate was recor-ded as late as after 60 min of xylasine-induced seda-tion. Considering these facts, it appears that a faster return of the respiratory rate to the initial values was associated with a lower dose of xylasine used for pre-medication. The most common side-effect of the propofol administration is a respiratory depression com-bined with gas exchange disturbances (17). The preme-dication and anaesthesia induction in groups I and II produced a decline of hydrogen ion concentration that persisted during the halothane anaesthesia. In both groups the partial pressure of carbon dioxide increased after premedication and remained at an elevated level throughout anaesthesia. An elevated partial pressure of carbon dioxide was also observed in the dogs pre-medicated with medetomidine and midazolam and then anaesthetised with propofol (8).
The incidence of respiratory depression was associa-ted with some disturbances in arterial blood oxygena-tion manifested by increased PaO2 and SatO2, which occurred in both groups.
Considering the complete clinical picture, the distur-bances in acid-base balance parameters, it may be stated that under the premedication and propofol induc-tion in the halothane inhalainduc-tion anaesthesia, acute respiratory acidosis occurred in group I and II.
In conclusion, the presented research results demon-strate that propofol induces loss of consciousness in the animals premedicated with xylasine or xylasine and midazolam at the mean doses of 3.12 and 3.13 mg/kg bw. respectively. Premedication with xylasine alone or xylasine in a twofold smaller dose administered in com-bination with midazolam does not affect the dose of propofol required to induce loss of consciousness. The patients undergoing the premedication with midazolam and xylasine and then anaesthetized with propofol show a reduced vomiting rate and need a shorter time to regain consciousness and motor function compared to those premedicated with xylasine alone.
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