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. 2022 Feb 4;10(1):4.
doi: 10.1186/s40635-022-00432-z.

Effects of norepinephrine infusion on cerebral energy metabolism during experimental haemorrhagic shock

Rasmus Peter Jakobsen  1   2 , Elisabeth Charlotte Hansen  3 , Troels Halfeld Nielsen  4 , Carl-Henrik Nordström  4   5 , Palle Toft  6   3
Affiliations

Effects of norepinephrine infusion on cerebral energy metabolism during experimental haemorrhagic shock

Rasmus Peter Jakobsen et al. Intensive Care Med Exp. .

Abstract

Background: The use of norepinephrine in the case of life-threatening haemorrhagic shock is well established but widely discussed. The present study was designed to compare the effects of early norepinephrine treatment vs. no treatment on cerebral energy metabolism during haemorrhagic shock.

Methods: Twelve pigs were subjected to haemorrhagic shock, 4 in the control group and 8 in the norepinephrine (NE) group. Following a 60 min baseline period haemorrhagic shock was achieved by bleeding all animals to a pre-defined mean arterial blood pressure (MAP) of approximately 40 mm Hg. When mean arterial pressure had decreased to 40 mmHg NE infusion started in the treatment group. After 90 min, NE infusion stopped, and all pigs were resuscitated with autologous blood and observed for 2.5 h. During the experiment cerebral tissue oxygenation (PbtO2) was monitored continuously and variables reflecting cerebral energy metabolism (glucose, lactate, pyruvate, glutamate, glycerol) were measured by utilizing intracerebral microdialysis.

Results: All 12 pigs completed the protocol. NE infusion resulted in significantly higher MAP (p < 0.001). During the shock period lactate/pyruvate (LP) ratio group increased from 20 (15-29) to 66 (38-82) (median (IQR)) in the control group but remained within normal limits in the NE group. The significant increase in LP ratio in the control group remained after resuscitation. After induction of shock PbtO2 decreased markedly in the control group and was significantly lower than in the NE group during the resuscitation phase.

Conclusion: NE infusion during haemorrhagic shock improved cerebral energy metabolism compared with no treatment.

Keywords: Cerebral metabolism; Haemorrhagic shock; Microdialysis; Norepinephrine; Trauma.

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Conflict of interest statement

Rasmus Peter Jakobsen, Elisabeth Charlotte Hansen, Troels Halfeld Nielsen, Carl-Henrik Nordström and Palle Toft declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Experimental protocol timeline. Note that the experimental protocol is divided into four intervals. Interval 1: Baseline − 60–0 min. Interval 2: Hypoperfusion period 0–90 min, Interval 3: Stabilisation period 90–180 min in which physiological state might return to homeostasis. Interval 4: post-resuscitation period 180–240 min
Fig. 2
Fig. 2
Dynamic changes of median (interquartile range) mean arterial pressure (MAP) throughout the experiment. NE group n = 8. Control group n = 4. Note the steep decrease in MAP in both groups at the start of hypoperfusion period. In addition, note the normalisation of MAP after start of NE infusion. Shaded area illustrates hypoperfusion period
Fig. 3
Fig. 3
Median (interquartile range) values of lactate, pyruvate and glucose concentrations in the hemisphere in the controls and NE group during the experiment. Note that the increase in LP ratio in the control group during hypoperfusion is due to an increase in lactate simultaneously with a decrease in pyruvate. After resuscitation the lactate levels in the control group remains elevated but he pyruvate levels trends towards normalising. In addition, note the normalisation of glucose in the control group after resuscitation. Control n = 4. NE group n = 8; loq lower quartile, upq upper quartile
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