Tlenek azotu i siarkowodór – markery w ostrej fazie urazu wielonarządowego

Nataliya Matolinets, Helen Sklyarova, Alexander Sklyarov

Danylo Halytsky Lviv National Medical University, Lviv, Ukraine

ABSTRACT

Introduction: Polytrauma or multiple organ damage is connected with shock and organ failure, which in severely injured patients and if untreated quick can lead to death.).

The aim: To investigate levels of NO, NOx and H2S in patients with acute trauma period at the time of hospitalization and for 24 hours after trauma.

Materials and method: Etiology of trauma: traffic accident – 78 %, drop from the altitude – 5 %, everyday trauma – 17 %. Blood tests were performed during patient admission and 24 hours after admission.

Results: Results of the study in patients with severe polytrauma showed increase of serum NO and its metabolites, but decrease of H2S. Suggest increase of NОx is connected with severity of trauma and can be as indicator of prognosis for severity of injury in polytrauma. So detection of NO and its metabolites and H2S can be use as early markers of detection for severity of polytrauma.

Conclusions: Intensive care management in acute polytrauma period leads to increase of NO level and its metabolites on the background of H2S decrease. Detection of NO, NOx, H2S and valuation of its balance in acute period of polytrauma can serve as severity indicators and prognosis of these disease. In comparation to general clinical parameters, gasotrasmitters react on changes in homeostasis faster and more sensitive what allows to use them more widely as biomarkers of organ disfunction development in acute polytrauma period.

Wiad Lek 2018, 71, 8, -1491

INTRODUCTION

Polytrauma or multiple organ damage is connected with shock and organ failure, which in severely injured patients and if untreated quick can lead to death. It’s well known that every tissue damage is related to systemic inflammation, oxidative stress and endothelial dysfunction [1]. Endothelial dysfunction is characterized by release and decrease of different mediators, especially gaseous messengers, such as Nitric Oxide (NO), Hydrogen sulfide (H2S) and Carbon monooxide (CO). In recent years these substances, especially NO and H2S and their role in endothelial dysfunction track attention of many scientists [2].

NO parts in regulation of metabolic processes and helps to maintain human homeostasis. It has a wide range of action and is involved in control of circulation, neurotransmission and immunomodulation [3]. NO also has a protective role in vascular tone, as it prevents intravascular thrombosis by inhibition of platelets adhesion and neutralization oxygen free radicals. But in special conditions it can exert a proinflamatory effects [4]. Investigations, focused on different aspects of biological action of NO don’t loose its actuality and are quite promising [5].

H2S is synthesized from L-cystein by three enzymes: cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST) in cooperation with cysteine aminotransferase (aspartate aminotransferase). It is believed that this gas is generated in vesseles, kidney and brain [6]. It stimulates ATP- dependent potassium channels in smooth vascular cells, neurons and nephrons, taking part in vascular tone regulation [7,8]. H2S in contrast to NO, has as vasorelaxing, then vasoconstricting effects [4]. But they are not fully understood.

There are many classifications of polytrauma due to its severity, but they are not acute and have many disadvantages [9]. There is a need to find an indicator, that could serve as a marker dependent on severity of polytrauma.

THE AIM

To investigate levels of NO, NOx and H2S in patients with acute trauma period at the time of hospitalization and for 24 hours after trauma.

MATERIALS AND METHODS

The investigation included 25 patients with polytrauma, who undergo treatment in Lviv Emergency Hospital. Hospitalization period was 0,5 hours.

Demographic period included age, sex and causes of polytrauma. Mean age of all patients was 38,4±5,2 years. Patients with comorbidities were excluded from investigation. In total 25 individuals 19 were male and 6 were female. Etiology of trauma: traffic accident – 78 %, drop from the altitude – 5 %, everyday trauma – 17 %.

The severity of patient injury was determined according to the ISS scoring system. Based on clinical state and ISS score this group of patients was suffered from mild and severe polytrauma. All subjects evaluated before and after shock therapy. Blood tests were performed during patient admission and 24 hours after admission. Initial blood tests were taken to assess the serum concentration of NO, NOx, H2S, glycaemia, total protein, creatinine, bilirubin, fibrinogen, hematology (hemoglobin, hematocrit).

All patients undergo standard physical, laboratory and instrumental examination due to Advanced trauma life support (ATLS®): the ninth edition. ATLS Subcommittee; American College of Surgeons, Committee on Trauma (2013).

Exept standard examination additional blood samples for NO and H2S were taken. Level of NO and the sum NO2 + NO3 (NOx) was measured by Griess method [10]. Level of H2S was measured by reaction with N,N-dymetil-para-fenildyamin catalized bу FeCl3.

Non-invasive central hemodynamic parameters, arterial gasometry, abdomen and chest ultrasound, chest, pelvis, skull and spine X-ray, brain and body computed tomography, thoraco- and laparocentesis (if indicated) were performed in all consecutive cases. Diagnostic and antishock measures were held simultaneously.

Antishock therapy suggested control of bleeding, adequate pain relief, providing of adequate gases’ metabolism. A volume of infusion was determined on the base of circulating blood volume deficite with targeted compensation of acute blood loss. Urgent surgical procedures were performed for salvage of a patient’s life. Each patient underwent the correction of water-electrolyte balance and metabolic violations, respiratory support if needed, antibacterial therapy, analgosedation, correction of hemostasis disorders, symptomatic therapy.

Continuous characteristics were represented using means and standard deviations. Independent Student t-test was used to compare differences between the different groups. Analysis of data was performed and expressed as (mean ± SD).

RESULTS AND DISCUSSION

During analyses of damage severity it was revealed that among investigated group of patients major were modest damage (ISS and APACHE II). Intensive care therapy and surgical treatment in patients during first 24 hours leads to improvement of hemodynamic parameters. On the second day was noticed increase of systolic blood pressure and decrease of heartburn. During first 24 hours diuresis was from 800 to 1300 ml. Standartization of hemodynamic parameters and 24-hours diuresis evidenced about patients improvement from traumatic shock.

Systemic inflammation developed after traumatic shock and manifested by increase of systemic inflammation indicators (leucocitosis, neutrofilosis), hyperglycemia, hyperfibrinemia, and subfebrile body temperature. Blood biochemical parameters during hospitalization were in the range of normal levels. But albumin and prothrombin index (PTI) decrease on the second day while fibrinogen and glucosae increase (Table I).

Mean Levels of NO in patients with polytrauma increases from 0,34±0,02 μmol/ L to 0,43±0,03 μmol/ L after 24- hours of intensive therapy.

Mean level of NOx in blood of patients during hospitalization was 2,29±0,13 μmol/ L . After intensive care management level of NOx increases and was 2,80±0,14 μmol/ L on the second day.

Investigation of H2S dynamic in blood during hospitalization detected mean level of this parameter – 64,23±1,22 μmol/ L. During intensive care level of H2S decreases and reached 58,9±1,25 μmol/ L.

Results of the study in patients with severe polytrauma showed increase of serum NO and its metabolites, but decrease of H2S. As Beitl et al. (2017), suggest increase of NОx is connected with severity of trauma and can be as indicator of prognosis for severity of injury in polytrauma [11].

On the other hand hydrogen sulfide play important role in regulation of vascular hemostasis and has anti-inflammatory and cytoprotective effects. Decrease of H2S can be a sign of proinflammatory effect and this is convinced by NO and NOx increase on first day after polytrauma.

Positive correlation between NOx and H2S (r=0,41) and negative correlation between NO and NОx (r=-0,41) also attract attention and sign about processes that occur during trauma.

During trauma cross interaction between NO and its metabolites happens and this is сonfirmed by positive correlation between NОx and H2S (r=0,40) and negative by NO-NOx (r=-0,50).

CONCLUSIONS

1. Intensive care management in acute polytrauma period leads to increase of NO level and its metabolites on the background of H2S decrease.

2. Detection of NO, NOx and H2S and valuation of its balance in acute period of polytrauma can serve as indicators of severity and prognosis of polytrauma.

3. In comparation to general clinical parameters, gasotrasmitters react on changes in homeostasis faster and more sensitive what allows to use them more widely as biomarkers of organ disfunction development in acute period of polytrauma.

REFERENCES

1. Lo Faro MLFox BWhatmore JLWinyard PG and Whiteman M. Hydrogen sulfide and nitric oxide interactions in inflammation. Nitric Oxide. 2014; 41:38-47.

2. Daiber A, Steven S, Weber A, et al. Targeting vascular (endothelial) dysfunction. Br J Pharmacol. 2016;174(12):1591-1619.

3. Moreira JD, Pernomia NL, Gomes MS, et al. Enhanced nitric oxide generation from nitric oxide synthases as the cause of increased peroxynitrite formation during acute restraint stress: Effects on carotid responsiveness to angiotensinergic stimuli in type-1 diabetic rats. Eur J Pharmacol. 2016;783:11-22.

4. Kolluru GK, Shen X, Kevil CG. A tale of two gases: NO and H2S, foes or friends for life? Redox Biol. 2013;1(1):313-318.

5. Hsieh HJ, Liu CA, Huang B, Tseng AH and Wang DL. Shear-induced endothelial mechanotransduction: the interplay between reactive oxygen species (ROS) and nitric oxide (NO) and the pathophysiological implications. J Biomed Sci. 2014;21:3.

6. Song Y, Wang L. Hydrogen sulfide and acute lung injury. World J of Pharm and Pharm Sci. 2016;5(12):367-386.

7. Zhao W, Zhang J, Lu Y, Wang R. The vasorelaxant effect of H2S as a novel endogenous gaseous KATP channel opener. EMBO J. 2001;20:6008–6016.

8. Chen X., Jhee K.H., Kruger W.D. Production of the neuromodulator H2S by cystathionine beta-synthase via the condensation of cysteine and homocysteine. J Biol Chem. 2004;279:52082–52086.

9. Chapleau W, Al-khatib J, Haskin D, et al. Advanced trauma life support (ATLS®): the ninth edition. ATLS Subcommittee; American College of Surgeons’ Committee on Trauma; International ATLS working group. J Trauma Acute Care Surg. 2013;74(5): 1363-1366.

10. Bryan NS, Grisham MB. Methods to detect nitric oxide and its metabolites in biological samples. Free Radic Biol Med. 2007;43(5):645-657.

11. Beitl E, Banasova A, Vlcek M, Mikova D, Hampl V. Nitric oxide as an indicator for severity of injury in polytrauma. Bratislava Medical Journal. 2016;116(4):217-220.

Authors’ contributions:

According to the order of the Authorship.

Conflict of interest:

The Authors declare no conflict of interest.

CORRESPONDING AUTHOR

Nataliya Matolinets

Department of anesthesiology and intensive care FPGE

Danylo Halytsky Lviv National Medical University, Lviv, Ukraine

tel: +380677741348

e-mail: nmatolinets@gmail.com

Received: 14.07.2018

Accepted: 11.10.2018

Table I. Comparable levels of NO, NOx, H2S and biochemical parameters in patients in different trauma periods

Acute period

After 24-hours

P-value

NO, μmol/L

0,34±0,02

0,43±0,02

p<0,01

NOx, μmol/L

2,29±0,13

2,80±0,14

p<0,01

H2S, μmol/L

64,23±1,22

58,97±1,25

p<0,01

Hemoglobin, g/L

91,36±2,40

87,00±2,06

p>0,05

Hematocrite, %

30,40±1,14

29,28±0,87

p>0,05

Creatinin, μmol/L

84,60±6,95

102,55±6,99

p<0,05

Urea, mmol/L

9,33±0,85

11,03±0,65

p>0,05

Protein, g/L

58,36±0,90

35,82±4,94

p<0,01

Glucose, mmol/L

5,66±0,14

7,47±0,27

p<0,01

Fibrinogen, g/L

3,72±0,18

9,52±1,16

p<0,01

PTI, %

92,48±1,45

58,20±8,76

p<0,01