Propofol was given to effect in group I (control), whereas, meperidine @2 mg/kg bwt and pentazocine@ 2 mg/kgbwt was given as preanaesthetic before propofol “to effect” in dogs of group II and III, respectively. Atropine sulphate was injected I/M @ 0.04 mg/kg b. wt. 20 minutes prior to each treatment in all the groups. A non significant alteration in the level of total serum protein, alkaline phosphatase activity, serum creatinine and blood urea nitrogen could be recorded at different observation periods either within the group or among the groups. There was significant increase in serum glucose level at 1hr in all the three treatment groups. There was significant increase (P<0.05) in SGOT value at 1hr in group I whereas in group II and III it could be recorded at hr 1 and 2 of observation followed by a progressive decrease in its value which reached to pre-treatment level within 24 hr in all the treatment groups. A significant elevation (P<0.05) in SGPT value could be recorded in all the groups of animals at hr1 and 2 of observation as compared to their respective baseline value. In conclusion, meperidine or pentazocine along with propofol administration in dogs revealed least and variable changes within the normal physiological limits, hence considered as suitable anesthetic in terms of least effects on vital organs.
Balanced anesthesia is achieved by administration of multiple drugs. Drugs are targeted to specifically attenuate individual components of the anesthetic state; that is, consciousness, analgesia, muscle relaxation, and alteration of autonomic reflexes (Thurmon and Short, 2007). In Addition to the hypnotic agent, such as propofol, opioids are often used due to their synergistic hypnotic and analgesic properties (Kortelainen et al., 2011). Meperidine is synthetic opioids that exert its analgesic effects through agonism at Mu receptors. Meperidine can be act like local anesthetic and alpha 2 agonist like properties (Wolff et al., 2004: Takada et al., 2002). Meperidine has been shown to produce significant negative inotropic effects in dogs. As compared to other opioids, meperidine tends to increase heart rate due to its atropine like effects (Branson et al.,2001). Pentazocine is classified as agonist- antagonist opioids and clinically similar to butorphanol. It induces mild analgesia accompanied by minimal sedation, respiratory depression or adverse cardiovascular effects. In the past, it was used in equine patients for management of colic pain but now it was replaced by the alpha 2 agonists, NSAID (Flunixin meglumine) and butorphanol (Lamont and Mathews, 2007).
Propofol a milky solution is a highly lipophilic with rapid onset, distribution and elimination phases after intravenous administration (Aguiar et al., 2001). Because of it shorter action, propofol needs combination with other drugs to prolong the anaesthesia of longer operative procedure. Ilkiw et al. (2003) reported that during combination of anaesthesia, each drug could partially attenuate the undesirable effects of the other. The safety and stability of propofol combination have been documented (Auckburally et al., 2008; Padilha et al., 2011). Moreover, drug combinations typically reduce the dose of general anaesthesia or other anaesthetic which may be beneficial in certain situations (Smischney et al., 2012). Various workers have studied the changes in haemato-biochemical parameters following administration of xylazine and propofol (Dewangan et al., 2016), buprenorphine and propofol (Anandmay et al., 2016). There is lack of data related to biochemical profiles with the meperidiine, and pentazocine as opioids in combination with propofol. Hence, the present paper deals with the changes in the biochemical parameters following administration of different opioids as preanaesthetic agents in combination with propofol as induction agent.
Material and Methods
The study was conducted in 15 non descript dogs of either sex of aged 1-2 yrs and weighing between 15-20 kg, randomly divided in to three groups with five dogs in each group. Propofol was given “to effect” in group I (control), whereas meperidine @2 mg/kg bwt and pentazocine@ 2 mg/kgbwt was given as preanaesthetic 15 min before propofol “to effect” in dogs of group II and III, respectively. Atropine sulphate was injected I/M @ 0.04 mg/kg b.wt. 20 minutes prior to each treatment. Propofol ‘to effect” was administered intravenously in each animal of three groups, after administration of pre-anaesthetic agents to produce general anaesthesia till the loss of pedal reflex which served as a guide for the development of surgical anaesthesia. Blood sample was collected for determination of base value (0 hr) for different haematological and bio-chemical parameters. This experimental study was approved by institutional ethical committee.
Following administration of propofol, haematological parameters viz. Hb, PCV, TEC, TLC, DLC, and platelets was carried out at the time intervals of 5, 10, 20, 30 and 60 minutes. Venous blood samples were collected at 1 hr, 2 hr, 4 hr and finally at 24 hr for the estimation of different bio-chemical parameters. For harvesting blood serum, 4-5 ml of blood was collected before and at time intervals of 1 hr, 2 hr, 4 hr and finally at 24 hr in a clean and dry test tube without anticoagulant by dry glass syringe through siliconized catheter placed in radial vein or recurrent tarsal vein. The blood was allowed to clot within the test tube in a standing position for nearly 30 minutes and then centrifuged it for 20 minutes at 3500 rpm. The supernatant serum was collected in a clean dry test tube by rubber bulb pipette. The separated serum was used for estimation of serum protein (Biuret method), alkaline phosphatase (Tris carbonate buffer method), serum creatinine (Jaffe’s method), serum urea nitrogen (GLD – urease method); ALT (IFCC method), AST (IFCC method) and GGT (IFCC method) were carried out by Auto analyzer (Erba Mannheim Chem-5 plus V2) using Erba diagnostic kit. The data obtained were statistically analyzed by standard method and technique as outlined by Snedecor and Cochran (2004).
Results and Discussion
At 5 min of observation after administration of propofol anaesthesia, groups I and III exhibited significant fall (P<0.05) in Hb and PCV whereas at 10 min of observation, TEC showed significant fall in all the three groups (Table I).
The value of PCV in group II and III differed significantly with other groups of animals at 5 and 10 min of observation, respectively. The values of TLC, DLC and platelets did not show any significant difference (P>0.05) at any time intervals either within or among the groups. The decrease in Hb, PCV and TEC values might due to splenic pooling of blood following administration of anaesthetic agents (Hewson et al., 2006; Welberg et al., 2006). A significant decline in TEC using buprenorphine and propofol (Anandmay et al., 2016), propofol (Venugopal et al., 2002), xylazine -propofol (Dewangan et al., 2016) has been reported in dogs. In contrary to this, haematological parameters were non-significantly variable with the use of midazolam – pentazocine in propofol anaesthesia in buffalo (Saibaba et al., 2016). The total serum protein level did not show any significant variation (P>0.05) at any interval of time either within the group or among the groups (Table 1). Similar finding was recorded by Bayan et al. (2002), and Chandrashekharappa and Ananda (2009) using different combinations of anaesthetic with propofol in canine. The measurement of total serum protein is of limited value. It may be altered by change in plasma volume; an increase is caused by dehydration and a decrease from overload with water (Gowenlock, 1996). The non-significant alteration in total serum protein in all the groups might be due to splenic pooling of erythrocytes which caused overloading of water in blood.
Table 1: Mean ± S.E. value of haemoglobin (gm/dl), PCV (%) and TEC (x106 µl of blood) of different groups at different time intervals of observation
|Parameters||Group||Period of Observation (in minutes)|
|Hb||I||10.72±0.28a||9.35±0.23Ab||10.70±0.12 a||10.50±0.18a||10.75±0.26 a||11.00±0.19a|
|II||11.60±0.52a||10.90±0.43Cab||10.22±0.51 b||10.98±0.07ab||11.20±0.07ab||11.82±0.3 a|
Group I- propofol; Group II- Meperidine + Propofol ; Group III- Pentazocine +Propofol; Values with same superscripts in a column (capital letters) did not differ significantly (P>0.05); Values with same superscripts in a row (small capital letters) did not differ significantly (P>0.05)
A non-significant alteration in the level of alkaline phosphatase activity could be recorded at different observation periods within the group or among the groups (Table 1). However, the elevation in its value could be observed during the initial phase of anaesthesia.
Table 2: Mean ± S.E. value of total protein (TP) (gm/dl), alkaline phosphatase (IU/L), creatinine (mg/dl), blood urea nitrogen (mg/dl) of different groups at different time intervals of observation
|Parameters||Group||Period of Observation (hours)|
Group I – propofol; Group II- Meperidine + Propofol; Group III- Pentazocine +Propofol; Values at respective intervals within and between groups did not differ significantly (P>0.05)
The present finding corroborates with the finding of Apaydin et al. (2006) using diazepam – propofol combination in dog. Similar finding was also observed by Kashifard et al. (2010) in humans using propofol. Alkaline phosphatase is present in most tissues, richest source being osteoblasts in bone, bile canaliculi in liver and small intestinal epithelium. The alkaline phosphatase of normal adult appears to be mainly derived from liver with a small variable intestinal component (Gowenlock, 1996). The non significant alteration in alkaline phosphatase in all the groups might be due to neither bone damage nor any deleterious effect on kidney by propofol alone or with meperidine and pentazocine. The values of creatinine and serum urea nitrogen were transiently and non – significantly increased (P>0.05) at initial intervals after administration of agents. However, the values returned towards the base value by end of observation. Propofol along with meperidine and pentazocine were excreted mainly through kidney so estimation of BUN and creatinine becomes necessary to access kidney function. The finding of this study was similar to Kim and Jang (1999), Chandrashekharappa and Ananda (2009) in dog.
Table 3: Mean ± S.E. value of glucose (mg/dl), AST (IU/L) and ALT ((IU/L)) of different groups at different time intervals of observation
|Parameters||Groups||Period of Observation (hours)|
|Glucose||I||77.00 ± .79a||81.00 ± 1.67Ab||75.80 ± 1.51ab||78.00 ±.80Aab||78.00 ±0.94Aab|
|II||73.80 ± 1.79a||78.00 ±0.57ABb||72.60 ± 1.51a||73.86 ±0.67Ba||74.82±0.93BCab|
|III||74.68 ± 1.81a||79.20 ± 0.52Bb||73.92 ± 1.67a||75.00±1.11Bab||76.08±0.89Cab|
|AST||I||34.52 ± 0.35a||36.54 ±0.20ABb||35.78±0.33ABb||34.58± 0.30 a||34.60 ± 0.44a|
|II||34.84 ± 0.77a||37.16 ± 0.66 Bb||37.74 ±0.41Cb||34.94± 0.91 a||34.88± 0.66a|
|III||34.46 ± 0.32a||35.70 ± 0.21Ab||34.82±0.41Aab||34.78±0.30ab||34.42 ± 0.30a|
|ALT||I||41.80 ± 0.30a||42.94 ±0.20ABb||42.06±0.42Aab||41.46 ± 0.28a||41.5 ± 0.34a|
|II||41.58 ± 0.30a||42.36 ± 0.18Bb||42.51 0.19ABb||41.36 ± 0.36a||41.32 ± 0.11a|
|III||42.34 ± 0.28a||43.16 ± 0.19Ab||43.32 ±0.33Bb||42.14 ± 0.37a||42.08 ± 0.12a|
Group I- propofol, Group II- Meperidine + Propofol , Group III- Pentazocine +Propofol; Values with same superscripts in a column (capital letters) and row (small leters) did not differ significantly(P>0.05)
The non significant alteration in creatinine and blood urea nitrogen value might be due to no any muscular degeneration and increased level of anti diuretic hormone (ADH) along with decreased glomerular filtration during anaestheic procedure in all the groups. Contrary to this Singh et al.(2014) reported significant increase in creatinine levels after administration of xylazine and midazolam on propofol – halothane anaesthesia in dog.
Increased blood glucose level suggests hyperglycemia in all the groups after administration of propofol along with opioids. In all the groups a transient but significant increase in glucose level was observed at 1 hr post induction. The maximum increase in blood glucose level was noticed at 1 hr which tended to reach near the base value at 24 hr post induction in all the groups. This corroborates with the finding of Bayan et al. (2002) with propofol anaesthesia in dogs. Bayan et al. (2007) and Butola and Singh, (2003) also recorded hyperglycaemia using propofol-midazolam in canine. Similarly, administration of xylazine (Cwiek et al., 2009), propofol – ketamine (Khan et al., 2014) has also been reported to cause hyperglycemia. Kumar et al. (1989) observed a significant increase (P<0.05) in glucose level, studying biochemical effect of a combination of meperidine and diazepam in dogs. Rise in glucose level may be due to activation of the sympathoadrenal system releasing adrenaline which in turn mobilized glycogen from liver during anaesthesia. Sharif and Abouazra (2009) and Khan et al., 2014 have suggested that the stress with anaesthesia leads to alteration in endocrine secretion of insulin antagonists such as growth hormone and cortisol causing temporary diabetic state. Stress also activates the corticotropic releasing hormone (CRH) following the stimulation of hypothalamus. This hormone then stimulates ACTH and affects adrenal gland which then releases cortisol. Cortisol causes glycogenolysis in muscles as well as in liver (Genuth, 2004). Mild-to-moderate stress hyperglycemia is protective because it provides a source of fuel for the immune system and brain at a time of stress (Marik and Bellomo, 2013). In the present study the increased serum glucose level might be attributed to decreased membrane transport of glucose, decreased glucose utilization impaired insulin activity or increased concentration of adrenocortical hormones.
To assess the liver function tests, gama glutamyl transpeptidase (GGT), ALT and AST levels are often used as screening test (Kim et al., 2013). A non significant change in serum GGT value was recorded after induction of anaesthesia in all the groups. The finding of this study was similar to that of Apaydin et al., 2006, using propofol and diazepam in dogs. GGT catalyse the transfer of gamma glutamyl group from gamma glutamyl peptide to another peptide or to L amino acids or to water. The kidneys are the richest source of enzyme with appreciable amount in the liver, pancreas and prostate but with little in other tissue (Gowenlock, 1996). The non significant alteration might be due to no any deleterious effect on kidney and liver by propofol alone or with buprenorphine, meperidine and pentazocine. ALT and AST showed a significant increase (P<0.05) in all the groups during 1 hr to 2 hr post induction of propofol which gradually approached to preinjection value within 24 hrs of induction. The maximum increase in ALT and AST value was recorded in group III, 2hrs post induction of propofol.
Kumar et al. (1989) reported a significant increase (P<0.05) in SGOT level in dogs by using combination of meperidine and diazepam. Propofol is rapidly cleared by hepatic and perhaps, extrahepatic metabolism. It is mainly metabolized by glucoronide conjugation in liver (Kanto and Gepts, 1989). Meperidine has a shorter analgesic action and typically no extending beyond 1 hr. Most of the drug is demethylated to normeperidine in liver and then undergoes further hydrolysis and ultimately renal excretion (Buck 2011). Propofol along with pentazocine and meperidine are metabolized mainly in liver. So, the transient increase in ALT and AST level might be due to hepatic metabolism of these drugs which returned back to the normal physiological level indicating no undesirable effect on liver. Contrary to these Mukati et al., 2006 did not found significant alteration in xylazine – propofol anaesthesia.
Authors are thankful to Director Research, Birsa Agricultural University, and Dean, Ranchi Veterinary College, Kanke, Ranchi for providing necessary financial assistance to carry out this research work.