Effect of different doses of dexmedetomidine on microcirculation of rats with sepsis

doi:10.3877/cma.j.issn.1674-6880.2018.01.002

Abstract

Abstract:

Objective

To evaluate the effects of dexmedetomidine at different doses on the early microcirculatory system in septic rats.

Methods

A total of 48 Wistar rats were randomly divided into the cecal ligation and puncture (CLP) group, small-dose treatment group, medium-dose treatment group and large-dose treatment group, 12 rats in each group. The sepsis model was made by the CLP method, and dexmedetomidine was given respectively at the speed of 2.5 μg·kg^-1·h^-1, 5 μg·kg^-1·h^-1 and 10 μg·kg^-1·h^-1 to rats in small, medium and large-dose treatment groups through continuous tail vein pumping. The mean arterial pressure and heart rate at 1, 3, 5 h after CLP were recorded; arterial blood gas was measured at 3 h after CLP, including pH, partial pressure of carbon dioxide, partial pressure of oxygen, base excess in extracellular fluid, and levels of bicarbonate, total carbon dioxide, oxygen saturation and blood lactic acid; the death of rats in each group at 24 h was calculated.

Results

The heart rate and the level of mean arterial pressure in the four groups were significantly different (F=2.935, 3.862; P=0.005, 0.001). Compared with the CLP group, the mean arterial pressure of rats in small, medium and large-dose treatment groups decreased significantly at 1 h after operation (all P < 0.05), but there were no significant differences among the three groups at 3 h and 5 h after operation (all P > 0.05). However, the heart rate of rats in small, medium and large-dose treatment groups began to decrease at 3 h and 5 h after operation (all P < 0.05). The mean arterial pressure in the CLP group at 3 h and 5 h after operation was significantly lower than that at 1 h (all P < 0.05), while the heart rate of rats in the small, medium and large-dose treatment groups at 3 h and 5 h after operation was significantly lower than that at 1 h (all P < 0.05). The heart rate at 5 h after operation in the small and medium-dose treatment groups was significantly lower than that at 3 h (all P < 0.05). There were significant differences at the pH value [(7.27 ± 0.07), (7.17 ± 0.08), (7.12 ± 0.07), (7.13 ± 0.07)], partial pressure of carbon dioxide [(38 ± 8), (72 ± 21), (77 ± 24), (83 ± 16) mmHg], base excess in extracellular fluid [(-9.7 ± 3.9), (-3.2 ± 2.8), (-4.7 ± 3.4), (-2.0 ± 1.7) mmol/L], and levels of bicarbonate [(17.4 ± 3.3), (25.0 ± 2.7), (24.7 ± 4.2), (27.1 ± 1.7) mmol/L], total carbon dioxide [(18.6 ± 3.7), (27.1 ± 2.8), (26.9 ± 4.9), (29.6 ± 2.1) mmol/L], oxygen saturation [(97.8 ± 1.0)%, (97.2 ± 1.5)%, (93.9 ± 4.2)%, (94.4 ± 4.0)%] and blood lactic acid [(94.45 ± 4.01), (0.63 ± 0.66), (0.63 ± 0.43), (0.45 ± 0.38) mmol/L] in the four groups (F=21.902, 34.460, 30.096, 33.709, 33.988, 18.076, 39.916; all P < 0.05). In the same time, there was no significant difference in partial pressure of oxygen [(115 ± 17), (118 ± 23), (105 ± 19), (109 ± 22) mmHg; F=1.545, P > 0.05]. Compared with those in the CLP group, the pH value, partial pressure of carbon dioxide, base excess in extracellular fluid, bicarbonate, total carbon dioxide and blood lactic acid of rats in the small, medium and large-dose treatment groups were significantly different (all P < 0.05), and the oxygen saturation was significantly lower in the medium and large-dose treatment groups than in the CLP group (all P < 0.05). In addition, compared with the large-dose treatment group, the total carbon dioxide content and oxygen saturation in the small-dose treatment group and base excess in extracellular fluid in the medium-dose treatment group were significantly different (all P < 0.05). The proportional mortality indicator of the four groups (11/1, 9/3, 3/9, 2/10) was statistically significantly different (χ²=17.658, P=0.001), and it was significantly lower in the medium and large-dose treatment groups than in the CLP and small-dose treatment groups (all P < 0.008).

Conclusions

The continuous infusion of dexmedetomidine into CLP sepsis rats within 3 hours can significantly improve the microcirculatory system, decrease the heart rate and stabilize the mean arterial pressure. The survival of CLP sepsis rats can be obviously improved with the increased dose of dexmedetomidine.

Key words: Shock, septic, Dexmedetomidine, Microcirculatory system

Yan Ma, Tuerdi Baihetinisha·, Xiangyou Yu, Yi Wang, Yunlin Song. Effect of different doses of dexmedetomidine on microcirculation of rats with sepsis[J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2018, 11(01): 11-16.

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References 18

[1]	Marik PE. Early management of severe sepsis: conce-pts and controversies[J]. Chest, 2014, 145 (6): 1407-1418.
[2]	孙文武，毛恩强.微循环变化对于脓毒症患者液体复苏治疗的意义[J/CD].中华危重症医学杂志（电子版），2016，9（3）：201-204.
[3]	Miranda ML, Balarini MM, Bouskela E. Dexmedetomi-dine attenuates the microcirculatory derangements evoked by experimental sepsis[J]. Anesthesiology, 2015, 122 (3): 619-630.
[4]	马燕，于湘友.不同剂量右美托咪定对脓毒症大鼠早期免疫调节的影响[J].中华急诊医学杂志，2016，25（9）：1149-1153.
[5]	Sakr Y, Dubois MJ, De Backer D, et al. Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock[J]. Crit Care Med, 2004, 32 (9): 1825-1831.
[6]	Verdant CL, De Backer D, Bruhn A, et al. Evaluation of sublingual and gut mucosal microcirculation in sepsis: a quantitative analysis[J]. Crit Care Med, 2009, 37 (11): 2875-2881.
[7]	Secor D, Li F, Ellis CG, et al. Impaired microvascular perfusion in sepsis requires activated coagulation and pselectin-mediated platelet adhesion in capillaries[J]. Intensive Care Med, 2010, 36 (11): 1928-1934.
[8]	Taccone FS, Su F, Pierrakos C, et al. Cerebral micro-circulation is impaired during sepsis: an experimental study[J]. Crit Care, 2010, 14 (4): R140.
[9]	Pandharipande PP, Sanders RD, Girard TD, et al. Eff-ect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis of the MENDS randomized controlled trial[J]. Crit Care, 2010, 14 (2): R38.
[10]	Venn M, Newman J, Grounds M. A phase Ⅱ study to evaluate the efficacy of dexmedetomidine for sedation in the medical intensive care unit[J]. Intensive Care Med, 2003, 29 (2): 201-207.
[11]	Riker RR, Shehabi Y, Bokesch PM, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial[J]. JAMA, 2009, 301 (5): 489-499.
[12]	Pandharipande PP, Pun BT, Herr DL, et al. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial[J]. JAMA, 2007, 298 (22): 2644-2653.
[13]	Tan JA, Ho KM. Use of dexmedetomidine as a sed-ative and analgesic agent in critically ill adult patients: a meta-analysis[J]. Intensive Care Med, 2010, 36 (6): 926-939.
[14]	马燕，于湘友，王毅.不同剂量右美托咪定对脓毒症大鼠血流动力学的影响[J].中国急救复苏与灾害医学杂志，2017，12（9）：930-933.
[15]	Marik PE, Baram M. Noninvasive hemodynamic moni-toring in the intensive care unit[J]. Crit Care Clin,2007, 23 (3): 383-400.
[16]	Taniguchi T, Kidani Y, Kanakura H, et al. Effects of dexmedetomidine on mortality rate and inflammatory responses to endotoxin-induced shock in rats[J]. Crit Care Med, 2004, 32 (6): 1322-1326.
[17]	Taniguchi T, Kurita A, Kobayashi K, et al. Dose- and time-related effects of dexmedetomidine on mortality and inflammatory responses to endotoxin-induced shock in rats[J]. J Anesth, 2008, 22 (3): 221-228.
[18]	Qiao H, Sanders RD, Ma D, et al. Sedation improves early outcome in severely septic Sprague Dawley rats[J]. Crit Care, 2009, 13 (4): R136.

组别	只数	平均动脉压（mmHg）			心率（次/min）
组别	只数	1h	3h	5h	1h	3h	5h
CLP组	12	91.70 ± 18.23	71.47 ± 16.65^b	64.47 ± 21.90^b	271.30 ± 35.88	259.25 ± 43.18	259.7 ± 48.00
小剂量治疗组	12	73.13 ± 18.45^a	72.05 ± 20.95	60.38 ± 17.87	237.97 ± 57.09	180.35 ± 59.01^ab	133.72 ± 47.91^abc
中剂量治疗组	12	73.97 ± 20.83^a	69.94 ± 18.16	66.25 ± 24.40	241.95 ± 53.34	188.50 ± 55.45^ab	127.32 ± 53.39^abc
大剂量治疗组	12	65.12 ± 12.49^a	71.79 ± 16.25	69.82 ± 21.20	241.95 ± 43.05	181.76 ± 56.14^ab	133.58 ± 63.61^ab
F值	?	?	2.935	?	?	3.862	?
P值	?	?	0.005	?	?	0.001	?

组别	只数	平均动脉压（mmHg）			心率（次/min）
组别	只数	1h	3h	5h	1h	3h	5h
CLP组	12	91.70 ± 18.23	71.47 ± 16.65^b	64.47 ± 21.90^b	271.30 ± 35.88	259.25 ± 43.18	259.7 ± 48.00
小剂量治疗组	12	73.13 ± 18.45^a	72.05 ± 20.95	60.38 ± 17.87	237.97 ± 57.09	180.35 ± 59.01^ab	133.72 ± 47.91^abc
中剂量治疗组	12	73.97 ± 20.83^a	69.94 ± 18.16	66.25 ± 24.40	241.95 ± 53.34	188.50 ± 55.45^ab	127.32 ± 53.39^abc
大剂量治疗组	12	65.12 ± 12.49^a	71.79 ± 16.25	69.82 ± 21.20	241.95 ± 43.05	181.76 ± 56.14^ab	133.58 ± 63.61^ab
F值	?	?	2.935	?	?	3.862	?
P值	?	?	0.005	?	?	0.001	?

组别	只数	pH值	二氧化碳分压（mmHg）	氧分压（mmHg）	细胞外液剩余碱（mmol/L）	碳酸氢盐（mmol/L）	总二氧化碳含量（mmol/L）	氧饱和度（%）	血乳酸（mmol/L）
CLP组	12	7.27 ± 0.07	38 ± 8	115 ± 17	-9.7 ± 3.9	17.4 ± 3.3	18.6 ± 3.7	97.8 ± 1.0	3.19 ± 1.17
小剂量治疗组	12	7.17 ± 0.08^a	72 ± 21^a	118 ± 23	-3.2 ± 2.8^a	25.0 ± 2.7^a	27.1 ± 2.8^ab	97.2 ± 1.5^b	0.63 ± 0.66^a
中剂量治疗组	12	7.12 ± 0.07^a	77 ± 24^a	105 ± 19	-4.7 ± 3.4^ab	24.7 ± 4.2^a	26.9 ± 4.9^a	93.9 ± 4.2^a	0.63 ± 0.43^a
大剂量治疗组	12	7.13 ± 0.07^a	83 ± 16^a	109 ± 22	-2.0 ± 1.7^a	27.1 ± 1.7^a	29.6 ± 2.1^a	94.4 ± 4.0^a	0.45 ± 0.38^a
F值	?	21.902	34.460	1.545	30.096	33.709	33.988	18.076	39.916
P值	?	< 0.001	< 0.001	0.202	< 0.001	< 0.001	< 0.001	0.001	< 0.001

组别	只数	pH值	二氧化碳分压（mmHg）	氧分压（mmHg）	细胞外液剩余碱（mmol/L）	碳酸氢盐（mmol/L）	总二氧化碳含量（mmol/L）	氧饱和度（%）	血乳酸（mmol/L）
CLP组	12	7.27 ± 0.07	38 ± 8	115 ± 17	-9.7 ± 3.9	17.4 ± 3.3	18.6 ± 3.7	97.8 ± 1.0	3.19 ± 1.17
小剂量治疗组	12	7.17 ± 0.08^a	72 ± 21^a	118 ± 23	-3.2 ± 2.8^a	25.0 ± 2.7^a	27.1 ± 2.8^ab	97.2 ± 1.5^b	0.63 ± 0.66^a
中剂量治疗组	12	7.12 ± 0.07^a	77 ± 24^a	105 ± 19	-4.7 ± 3.4^ab	24.7 ± 4.2^a	26.9 ± 4.9^a	93.9 ± 4.2^a	0.63 ± 0.43^a
大剂量治疗组	12	7.13 ± 0.07^a	83 ± 16^a	109 ± 22	-2.0 ± 1.7^a	27.1 ± 1.7^a	29.6 ± 2.1^a	94.4 ± 4.0^a	0.45 ± 0.38^a
F值	?	21.902	34.460	1.545	30.096	33.709	33.988	18.076	39.916
P值	?	< 0.001	< 0.001	0.202	< 0.001	< 0.001	< 0.001	0.001	< 0.001

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