Safety and efficacy of ketamine xylazine along with atropine anesthesia in BALB/c mice

Jamal, Muhammad Ameen; Ahmed, Arslan Mahmood; Tahir, Muhammad; Ashraf, Muhammad; Sattar, Abdul; Ghafoor, Aamir; Munir, Shahzad; Ahmed, Irfan; Hussain, Mubashir; Riaz, Amjad

doi:10.1590/s2175-97902019000317231

Acessibilidade / Reportar erro

Brasil

Brazilian Journal of Pharmaceutical Sciences

Español English

Brasil

Español English

sumário « anterior atual seguinte »

Sumário

Original Article • Braz. J. Pharm. Sci. 55 • 2019 • https://doi.org/10.1590/s2175-97902019000317231 copy

Safety and efficacy of ketamine xylazine along with atropine anesthesia in BALB/c mice

Authorship SCIMAGO INSTITUTIONS RANKINGS

Anesthetics are an indispensable prerequisite for surgical intervention and pharmacological animal studies. The objective of present study was to optimize the dose of ketamine (K) and xylazine (X) along with atropine sulfate (A) in order to achieve surgical tolerance in BALB/c mice. Several doses of ketamine (100, 150, 200 mg/kg) and xylazine (10, 15, 20 mg/kg) were mixed and combination of nine doses (K/X: 100/10, 100/15, 100/20, 150/10, 150/15, 150/20, 200/10,200/15,200/20) were evaluated (n=9 per combination). A constant dose of atropine (0.05 mg/kg) was also used to counter side effect. Time-related parameters were evaluated on the basis of reflexes. KX at dose 200/20 mg/kg produced surgical tolerance in all nine mice with duration 55.00±6.87 minutes. The induction time 0.97±0.09 minutes, sleeping time 90.67±5.81 minutes and immobilization time (102.23±6.83 minutes) were significantly higher than all combination. However, this combination was considered unsafe due to 11 % mortality. While, KX at dose 200/15 mg/kg results in none of the mortality, so was considered as safe. Moreover, this combination produces surgical tolerance in 89 % mice with duration (30.00±7.45 minutes). It was concluded that KX at dose 200/15 mg/kg along with atropine 0.05 mg/kg is safe for performing surgical interventions in BALB/c mice.

Keywords:
Ketamine hydrochloride; Xylazine hydrochloride; Atropine sulfate; Surgical tolerance; BALB/c mice

Time	Definition	Intervals
T0	Time of injection	T0-T1-Induction Time
T1	Loss of righting reflex	T1-T3-Immobilization
T2	Loss of motion	T1-T4-Sleeping Time
T3	Spontaneous Movement	T3-T4-Recovery Period
T4	Regain of righting reflex

Anesthetic^* * Dose of atropine sulfate in all combination was constant (0.05 mg/kg), Number ofmice in each group were constant (n= 9), Depth and quality of anesthesia was characterized by use of reflex test and response to different stimuli, (mg/kg)	Ketamine 100 Xylazine 10	Ketamine 100 Xylazine 15	Ketamine 100 Xylazine 20	Ketamine 150 Xylazine 10	Ketamine 150 Xylazine 15	Ketamine 150 Xylazine 20	Ketamine 200 Xylazine 10	Ketamine 200 Xylazine 15	Ketamine 200 Xylazine 20
Safety margin
Surgical tolerance	5/9^a	5/9 ^a	3/9 ^ab	6/9 ^a	5/9 ^a	3/9 ^a	7/9^b	8/9 ^b	9/9 ^b
Death rate	0/9	0/9	0/9	0/9	0/9	0/9	0/9	0/9	1^ one mouse died during anesthesia, a-d denote significant difference (p<0.05) within row. Values with same letters denote non-significant difference (p> 0.05). /9
Time related parameters (minutes)
Induction Time	2.17±0.41^a	1.62±0.28^abc	1.77±0.29^ab	1.50±0.13^bcd	1.47±0.08 ^bcd	1.38±0.16 ^bcd	1.43±0.10 ^bcd	1.04±0.17 ^cd	0.97±0.09 ^cd
Immobilization	49.68±6.46^a	55.00±5.33^ab	49.40±4.94^b	67.83±6.24^ab	54.31±5.07^ab	77.27±14.10^b	83.25±6.48^b	66.87±12.47^ab	102.23±6.83^c
Duration of Surgical Tolerance	15.00±5.8^ab	11.66±4.78^b	6.66±4.16^b	18.33±7.12^ab	18.33±6.87^ab	8.33±4.48^b	19.44±6.37^ab	30.00±7.45^a	55.00±6.87^c
Sleeping Time	41.69±5.79^a	49.20±4.01^ab	41.77±4.46^a	56.69±4.96^abc	48.88±4.25^ab	64.10±12.27^ab	65.35±5.86^cd	55.05±10.96^abc	90.67±5.81^d
Recovery period	7.90±2.02^ab	10.25±2.69^ab	7.62±1.51^ab	11.13±1.97^abc	5.44±1.20^a	12.92±3.36^ac	18.12±3.82^c	11.85±3.38^abc	11.55±2.22^abc

Anesthetic^* * Dose of atropine sulfate in all combination was constant (0.05 mg/kg) Number of mice in each group were constant (n= 9), Depth and quality of anesthesia was characterized by use of reflex test and response to different stimuli, a-d denote significant difference (p<0.05) within row. Values with same letters denote non-significant difference (p> 0.05). (mg/kg)	Ketamine 100 Xylazine 10	Ketamine 100 Xylazine 15	Ketamine 100 Xylazine 20	Ketamine 150 Xylazine 10	Ketamine 150 Xylazine 15	Ketamine 150 Xylazine 20	Ketamine 200 Xylazine 10	Ketamine 200 Xylazine 15	Ketamine 200 Xylazine 20
Duration of various reflexes
Pedal withdrawal	15.00±5.83^ab	11.67±4.79^b	6.67±4.17^b	18.33±7.12^ab	18.33±7.12^ab	8.33±4.49^b	19.44±6.37^ab	30.00±7.45^a	55.00±6.87^c
Cutaneous	36.11±5.45^a	46.11±5.51^abc	39.44±5.10^ac	59.44±4.67b	45.56±4.20^abc	58.33±10.47^bc	65.00±7.02^bd	50.00±9.86^abc	82.78±7.46^d
Tail pinch	27.22±5.66^a	27.78±5.53^a	30.56±5.56^a	49.44±4.75^b	33.89±3.98^ab	36.67±8.98^ab	45.56±5.49^ab	45.56±9.73^ab	72.78±7.51^c
Corneal	33.33±5.27^a	43.33±5.46^ab	35.56±5.10^a	56.11±5.19b	41.67±3.54^ab	59.44±10.78^b	60.56±6.74^b	49.44±10.32^ab	82.78±7.46^c
Tactile stimuli	37.78±5.47^a	46.11±5.51^ab	41.11±4.98^ab	59.44±4.67^bc	46.11±4.39^ab	60.56±11.07^bc	67.78±7.17^cd	53.33±10.77^abc	82.78±7.46^d

Anesthetic^* * Dose of atropine sulfate in all combination was constant (0.05 mg/kg). Number of mice in each group were constant (n= 9), a-d denote significant difference (p<0.05) within row. Values with same letters denote non-significant difference (p> 0.05). (mg/kg)	Ketamine 100 Xylazine 10	Ketamine 100 Xylazine 15	Ketamine 100 Xylazine 20	Ketamine 150 Xylazine 10	Ketamine 150 Xylazine 15	Ketamine 150 Xylazine 20	Ketamine 200 Xylazine 10	Ketamine 200 Xylazine 15	Ketamine 200 Xylazine 20
Onset of various reflexes
Pedal withdrawal	8.50±1.70^abc	7.50±1.58^abc	7.50±2.50^abc	6.50±2.18^bc	5.00±1.58^c	14.17±0.83^a	10.94±2.16^ab	4.69±1.37^c	6.11±2.13^c
Cutaneous	0.50±0.50^ab	1.00±0.61^abc	1.67±0.83^ac	0.50±0.50^ab	0.83±0.53^abc	1.67±0.83^ac	1.88±0.41^c	0.63±0.41^ab	0.00±0.00^b
Tail pinch	2.50±0.00^a	3.00±0.50^ab	2.50±0.00^abc	2.50±0.00^a	3.33±0.83^ab	4.17±0.83^b	2.50±0.00^a	1.25±0.47^c	2.22±0.28^ac
Corneal	2.50±0.00^a	2.00±0.50^ab	2.50±0.00^a	2.50±0.00^a	2.50±0.00^a	2.50±0.00^a	2.50±0.00^a	1.25±0.47^b	0.28±0.28^c
Tactile stimuli	0.00±0.00	1.00±0.61^a	0.00±0.00	0.00±0.00	0.00±0.00	0.00±0.00	0.00±0.00	0.00±0.00	0.00±0.00

Universidade de São Paulo, Faculdade de Ciências Farmacêuticas Av. Prof. Lineu Prestes, n. 580, 05508-000 S. Paulo/SP Brasil, Tel.: (55 11) 3091-3824 - São Paulo - SP - Brazil
E-mail: bjps@usp.br

Acompanhe os números deste periódico no seu leitor de RSS

[1] *Correspondence: Amjad Riaz. Department of Theriogenology, University of Veterinary and Animal Sciences, Lahore, Pakistan. E-mail: riaz_amjad@yahoo.com