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Hydrogen Sulfide as Prognostic Factor (H2S-1)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2010 by University Medical Centre Ljubljana.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
University Medical Centre Ljubljana
ClinicalTrials.gov Identifier:
NCT01088490
First received: March 12, 2010
Last updated: March 16, 2010
Last verified: January 2010
  Purpose

Hydrogen sulfide (H2S), better known as a poisonous gas, has emerged as the third gaseous transmitter in mammals, next to nitric oxide (NO) and carbon monoxide (CO). Increased production and higher serum concentrations were shown in inflammatory diseases, septic shock and stroke. The investigators will test the hypothesis that higher serum H2S concentrations on admission to intensive care unit (ICU) are linked with higher mortality in patients with shock of any reason.


Condition
Mortality
Shock

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Hydrogen Sulfide as Prognostic Factor

Resource links provided by NLM:


Further study details as provided by University Medical Centre Ljubljana:

Primary Outcome Measures:
  • Prognostic value of H2S [ Time Frame: In hospital; ICU mortality 30days ] [ Designated as safety issue: Yes ]

    relationship between H2S and mortality of patients during intensive care treatment,

    comparison of H2S and lactate prognostic value



Secondary Outcome Measures:
  • Correlation of H2S with vasopressor requirements [ Time Frame: ICU treatmennt 30days ] [ Designated as safety issue: No ]
    relationship between H2S and dose of vasopressors (noradrenaline, epinephrine) used


Estimated Enrollment: 150
Study Start Date: January 2010
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
critically ill
Critically ill patients admitted to ICU

  Hide Detailed Description

Detailed Description:

Hydrogen sulfide (H2S), better known as a poisonous gas, has lately emerging as a third gaseous transmitter in mammals, next to nitric oxide (NO) and carbon monoxide (CO). H2S is present in most human tissues in concentrations up to 50 μM. Most of it is synthesized in brain, cardiovascular system, kidneys and liver. In human tissues H2S is synthesized from L-cysteine by two enzymes cystathionine-γ-lyase and cystathionine-β-synthase. H2S works by stimulating ATP sensitive potassium channels and is involved in regulation of vascular tone, myocardial contractility, insulin secretion and neurotransmission. In numerous animal models, H2S deficiency was shown in arterial and pulmonary arterial hypertension, Alzheimer's disease and liver cirrhosis. Increased production and higher serum concentrations were shown in inflammatory diseases, septic shock and stroke.

Most of studies so far were conducted on animals and already show some therapeutic potentials. In available literature there have been no studies in humans focused on H2S concentrations in critically ill and its prognostic value.

Hypothesis We will test the hypothesis that higher serum H2S concentrations on admission to ICU are linked with higher mortality in patients with shock of any reason.

Serum H2S concentrations are related to treatment support with vaso-active drugs (noradrenalin, epinephrine).

Material and methods In the study we will include adult patients admitted to medical ICU due to shock of any reason. Shock is defined as systemic arterial pressure lower than 90mmHg or drop for systemic arterial pressure at least 40mmHg for 15minutes or more with elevation of serum lactate value.

Patients will be included on basis of clinical appearance of shock - hypotension or need for vasopressors, brady- or tachycardia, signs of peripheral hypo perfusion, oliguria and changes in mental status.

Exclusion criteria: patient younger then 18years and patients not in shock

From blood samples drawn on admission to ICU we will measure H2S concentration. H2S concentration will be measured spectrophotometrically5 as first described in 19496 and further refined in 19657. Spectrophotometrical determination of H2S concentration in tissue and plasma was previously used by many researchers.3,8-11 Blood samples will be centrifuged as quickly after collection to obtain plasma. 200 μL of plasma will be mixed with pre-prepared solution of 100 μL 10% (wt/vol) trichloroacetic acid and 60 μL 1% (wt/vol) zinc acetate, to trap dissolved H2S. The mixture will be frozen at 20 C until further analysis.

After sufficient number of samples will be obtained, we will measure H2S concentration in series. 40µL 20 µM N,N-dimethyl-p-phenylenediamine sulfate in 7,2 M HCl and 40µL 30 µM FeCl3 v 1,2 M HCl will be added to unfrozen samples. After 10-20 min incubation at room temperature final mixtures will be centrifuged at 9000 rpm for 5 minutes to remove precipitate. After centrifugation absorption at 670 nm will be measured with spectrophotometer. All analysis will be done in duplicates.

Calibration curve of absorbance versus sulfide concentration will be obtained from known concentration of Na2S (0,699 µM - 69,93 µM) and concentrations of H2S in plasma calculated.

Impact of plasma H2S concentration on admission to ICU on ICU mortality will be observed trough nonparametric statistical analysis.

Expectations We hypothesize that higher serum H2S concentrations on admission to ICU in patients with shock of any cause are indicators of severity of shock and cardiovascular deterioration, related to treatment support with vaso-active drugs (noradrenalin, epinephrine). Thus higher serum H2S concentrations are expected to be better prognostic factor of ICU mortality in patients with shock than currently established lactic acid.

  Eligibility

Ages Eligible for Study:   18 Years to 95 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Critically ill patients how are admitted in shock or hemodynamicaly unstable ino intensive care

Criteria

Inclusion Criteria:

  • shock ( systemic arterial pressure less then 120mmHg, elevated lactate > 2.5mmol/L)

Exclusion Criteria:

  • patients admitted due to intoxication with H2S
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01088490

Contacts
Contact: Matej Podbregar, MD PhD +386 49 215960 podbregar.matej@gmail.com
Contact: Tomaž Goslar, MD +386 41362280 tomaz.goslar@gmail.com

Locations
Slovenia
University Medical Center Recruiting
Ljubljana, Slovenia, 1000
Contact: Matej Podbregar, MD PhD       Podbregar.matej@gmail.com   
Contact: Tomaž Goslar, MD    +38641362280    tomaz.goslar@gmail.com   
Sub-Investigator: Anja Jazbec, MD MSC         
Sub-Investigator: Tomaž Goslar, MD         
Sub-Investigator: Hugon Možina, MD MSc         
Sponsors and Collaborators
University Medical Centre Ljubljana
Investigators
Principal Investigator: Matej Podbregar, MD PhD University Medical Centre Ljubljana
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Matej Podbregar, UMC Ljubljana
ClinicalTrials.gov Identifier: NCT01088490     History of Changes
Other Study ID Numbers: H2S_1
Study First Received: March 12, 2010
Last Updated: March 16, 2010
Health Authority: Slovenia: Ministry of Health

Keywords provided by University Medical Centre Ljubljana:
Hydrogen sulfide
critically ill
mortality

Additional relevant MeSH terms:
Hydrogen Sulfide
Gasotransmitters
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 24, 2014