MortalityH2S-1NCT01088490
Hydrogen Sulfide as Prognostic Factor
An observational study of Mortality and Shock, run by University Medical Centre Ljubljana at 1 site in Slovenia.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 95 years
- How many people
- 50 participants
- Where
- 1 siteSlovenia
- Study dates
- Jan 2010to Jan 2014
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 95 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Critically ill patients how are admitted in shock or hemodynamicaly unstable ino intensive care
Who may be able to join
- shock ( systemic arterial pressure less then 120mmHg, elevated lactate > 2.5mmol/L)
Who cannot join
- patients admitted due to intoxication with H2S
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Keywords
- Hydrogen sulfide, critically ill, mortality
- Medical subject headings
- Shock, Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| critically ill | Critically ill patients admitted to ICU |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prognostic value of H2S
relationship between H2S and mortality of patients during intensive care treatment,
comparison of H2S and lactate prognostic value
Measured: In hospital; ICU mortality 30days
Secondary outcomes (1)
Correlation of H2S with vasopressor requirements
relationship between H2S and dose of vasopressors (noradrenaline, epinephrine) used
Measured: ICU treatmennt 30days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2010 (estimated)
- Study startJan 2010
- Primary completionJan 2012
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for MortalityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Centre Ljubljana
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Podbregar Matej, University Medical Centre Ljubljana
- Investigators
- Matej Podbregar, MD PhD, Principal investigator, University Medical Centre Ljubljana
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01088490
- Sponsor's protocol ID
- H2S_1
- Acronym
- H2S-1
- Status last verified
- Dec 2014
- First submitted
- 12 Mar 2010
- Last updated
- 5 Dec 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Lowicka E, Beltowski J. Hydrogen sulfide (H2S) - the third gas of interest for pharmacologists. Pharmacol Rep. 2007 Jan-Feb;59(1):4-24.
PubMed 17377202Hui Y, Du J, Tang C, Bin G, Jiang H. Changes in arterial hydrogen sulfide (H(2)S) content during septic shock and endotoxin shock in rats. J Infect. 2003 Aug;47(2):155-60. doi: 10.1016/s0163-4453(03)00043-4.
PubMed 12860150Mok YY, Atan MS, Yoke Ping C, Zhong Jing W, Bhatia M, Moochhala S, Moore PK. Role of hydrogen sulphide in haemorrhagic shock in the rat: protective effect of inhibitors of hydrogen sulphide biosynthesis. Br J Pharmacol. 2004 Dec;143(7):881-9. doi: 10.1038/sj.bjp.0706014. Epub 2004 Oct 25.
PubMed 15504752Li L, Bhatia M, Zhu YZ, Zhu YC, Ramnath RD, Wang ZJ, Anuar FB, Whiteman M, Salto-Tellez M, Moore PK. Hydrogen sulfide is a novel mediator of lipopolysaccharide-induced inflammation in the mouse. FASEB J. 2005 Jul;19(9):1196-8. doi: 10.1096/fj.04-3583fje. Epub 2005 Apr 29.
PubMed 15863703Lawrence NS, Davis J, Compton RG. Analytical strategies for the detection of sulfide: a review. Talanta. 2000 Aug 16;52(5):771-84. doi: 10.1016/s0039-9140(00)00421-5.
PubMed 18968036Zhang H, Zhi L, Moore PK, Bhatia M. Role of hydrogen sulfide in cecal ligation and puncture-induced sepsis in the mouse. Am J Physiol Lung Cell Mol Physiol. 2006 Jun;290(6):L1193-201. doi: 10.1152/ajplung.00489.2005. Epub 2006 Jan 20.
PubMed 16428267Collin M, Thiemermann C. Hydrogen sulfide and sulfite: novel mediators in the pathophysiology of shock and inflammation. Shock. 2005 Dec;24(6):595-6. doi: 10.1097/01.shk.0000188328.59770.25. No abstract available.
PubMed 16317393Abe K, Kimura H. The possible role of hydrogen sulfide as an endogenous neuromodulator. J Neurosci. 1996 Feb 1;16(3):1066-71. doi: 10.1523/JNEUROSCI.16-03-01066.1996.
PubMed 8558235Goslar T, Mars T, Podbregar M. Total plasma sulfide as a marker of shock severity in nonsurgical adult patients. Shock. 2011 Oct;36(4):350-5. doi: 10.1097/SHK.0b013e31822bcfd0.
PubMed 21897337
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hydrogen Sulfide as Prognostic Factor
- ClinicalTrials.gov ID
- NCT01088490
- Acronym / sponsor ID
- H2S-1 / H2S_1
- Keywords
- Hydrogen sulfide, critically ill, mortality
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University Medical Centre LjubljanaUniversity, hospital or other
- Study start
- Jan 2010
- Primary completion
- Jan 2012 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 17 Mar 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| critically ill | – | –Critically ill patients admitted to ICU |
Who may qualify
- Ages
- 18 to 95 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Critically ill patients how are admitted in shock or hemodynamicaly unstable ino intensive care
Key inclusion criteria (1 listed)
- shock ( systemic arterial pressure less then 120mmHg, elevated lactate > 2.5mmol/L)
Key exclusion criteria (1 listed)
- patients admitted due to intoxication with H2S
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Prognostic value of H2S
Time frame: In hospital; ICU mortality 30days
relationship between H2S and mortality of patients during intensive care treatment, comparison of H2S and lactate prognostic value
1 secondary outcome
Correlation of H2S with vasopressor requirements
Time frame: ICU treatmennt 30days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2014.
- Background: PubMed 17377202Lowicka E, Beltowski J. Hydrogen sulfide (H2S) - the third gas of interest for pharmacologists. Pharmacol Rep. 2007 Jan-Feb;59(1):4-24.
- Background: PubMed 12860150Hui Y, Du J, Tang C, Bin G, Jiang H. Changes in arterial hydrogen sulfide (H(2)S) content during septic shock and endotoxin shock in rats. J Infect. 2003 Aug;47(2):155-60. doi: 10.1016/s0163-4453(03)00043-4.
- Background: PubMed 15504752Mok YY, Atan MS, Yoke Ping C, Zhong Jing W, Bhatia M, Moochhala S, Moore PK. Role of hydrogen sulphide in haemorrhagic shock in the rat: protective effect of inhibitors of hydrogen sulphide biosynthesis. Br J Pharmacol. 2004 Dec;143(7):881-9. doi: 10.1038/sj.bjp.0706014. Epub 2004 Oct 25.
- Background: PubMed 15863703Li L, Bhatia M, Zhu YZ, Zhu YC, Ramnath RD, Wang ZJ, Anuar FB, Whiteman M, Salto-Tellez M, Moore PK. Hydrogen sulfide is a novel mediator of lipopolysaccharide-induced inflammation in the mouse. FASEB J. 2005 Jul;19(9):1196-8. doi: 10.1096/fj.04-3583fje. Epub 2005 Apr 29.
- Background: PubMed 18968036Lawrence NS, Davis J, Compton RG. Analytical strategies for the detection of sulfide: a review. Talanta. 2000 Aug 16;52(5):771-84. doi: 10.1016/s0039-9140(00)00421-5.
- Background: PubMed 16428267Zhang H, Zhi L, Moore PK, Bhatia M. Role of hydrogen sulfide in cecal ligation and puncture-induced sepsis in the mouse. Am J Physiol Lung Cell Mol Physiol. 2006 Jun;290(6):L1193-201. doi: 10.1152/ajplung.00489.2005. Epub 2006 Jan 20.
- Background: PubMed 16317393Collin M, Thiemermann C. Hydrogen sulfide and sulfite: novel mediators in the pathophysiology of shock and inflammation. Shock. 2005 Dec;24(6):595-6. doi: 10.1097/01.shk.0000188328.59770.25. No abstract available.
- Background: PubMed 8558235Abe K, Kimura H. The possible role of hydrogen sulfide as an endogenous neuromodulator. J Neurosci. 1996 Feb 1;16(3):1066-71. doi: 10.1523/JNEUROSCI.16-03-01066.1996.
- Derived from this study: PubMed 21897337Goslar T, Mars T, Podbregar M. Total plasma sulfide as a marker of shock severity in nonsurgical adult patients. Shock. 2011 Oct;36(4):350-5. doi: 10.1097/SHK.0b013e31822bcfd0.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matej Podbregar, MD PhD principal investigator
University Medical Centre Ljubljana
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Mortality and Shock, run by University Medical Centre Ljubljana at 1 site in Slovenia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Slovenia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prognostic value of H2S (time frame: In hospital; ICU mortality 30days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01088490, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2014.