Document Detail

New conclusive data on human myocardial dysfunction induced by acidosis.
Jump to Full Text
MedLine Citation:
PMID:  23134672     Owner:  NLM     Status:  Publisher    
ABSTRACT: Acidosis is one of the major consequences of hemodynamic instability in shock state patients directly associated with multiple organ failure evolution and death. Most studies on the hemodynamic consequences of acidosis have been experimental, nonhuman studies with severe acidosis, and thus far from the most common clinical situations. Schotola and colleagues offer a new approach to human failing myocardium where the authors highlight, ex vivo, the deleterious hemodynamic consequences of mild acidosis. Their work strengthens the current view of the urgent need to discover new efficient and nondeleterious therapy for the treatment of acidosis.
Antoine Kimmoun; Nicolas Ducrocq; Bruno Levy
Publication Detail:
Type:  EDITORIAL     Date:  2012-9-28
Journal Detail:
Title:  Critical care (London, England)     Volume:  16     ISSN:  1466-609X     ISO Abbreviation:  Crit Care     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-11-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9801902     Medline TA:  Crit Care     Country:  -    
Other Details:
Languages:  ENG     Pagination:  160     Citation Subset:  -    
INSERM, Groupe Choc, contrat Avenir INSERM, U961, Faculté de Médecine, 54511 Vandoeuvre les Nancy, France.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): Crit Care
Journal ID (iso-abbrev): Crit Care
ISSN: 1364-8535
ISSN: 1466-609X
Publisher: BioMed Central
Article Information
Download PDF
Copyright ©2012 BioMed Central Ltd
Print publication date: Year: 2012
Electronic publication date: Day: 28 Month: 9 Year: 2012
pmc-release publication date: Day: 28 Month: 9 Year: 2013
Volume: 16 Issue: 5
First Page: 160 Last Page: 160
PubMed Id: 23134672
ID: 3682263
Publisher Id: cc11520
DOI: 10.1186/cc11520

New conclusive data on human myocardial dysfunction induced by acidosis
Antoine Kimmoun123 Email:
Nicolas Ducrocq123 Email:
Bruno Levy123 Email:
1INSERM, Groupe Choc, contrat Avenir INSERM, U961, Faculté de Médecine, 54511 Vandoeuvre les Nancy, France
2CHU Nancy, Service de Réanimation Médicale Brabois, Pole Cardiovasculaire et Réanimation Médicale, Hôpital Brabois, 54511 Vandoeuvre les Nancy, France
3Université de Lorraine, 54000 Nancy, France

During the shock state, understanding the mechanisms of acidosis, its hemodynamic and inflammatory consequences as well as the best therapeutic approach remain an ongoing debate. In the previous issue, Schotola and colleagues provide, for the first time, new and en-lightening data on the consequence of acidosis in isolated human failing myocardium [1].

Over the past two decades, the mortality rate from a shock state has decreased; for instance, in septic shock from 30% to around 20% [2,3]. This improvement stems from many factors, including early management, more aggressive resuscitation with specific goals (volemic expansion, targeted main arterial pressure, blood transfusion, and so forth) and a better identification of prognostic factors such as acidosis [4]. As a major metabolic consequence of shock states, acidosis is also known to be a high predictor of in hospital mortality [5]. Both a cause and a consequence, this acidosis impairs cardiac and vascular function through various cellular and molecular mechanisms. Intracellular acidosis, which reduces myofilament sensitivity to Ca2+, is thus one of the crucial factors involved in myocardial dysfunction [6]. A low pH value also induces vessel hyporeactivity mediated by a number of factors such as nitric oxide, peroxynitrite, activation of KATP channels and modification of catecholamine signaling [7].

Although it has long been known that cardiovascular function is impaired by acidosis, the bulk of the studies have been mostly experimental, and only a few human studies have been relevant on this subject [8-10]. In the present study by Schotola and colleagues, the authors obtained ventricular trabeculae from human right ventricles explanted from failing hearts. These trabeculae were mounted in a chamber in which the development of isometric force was recorded and the tissues superfused with a HEPES solution at pH 7.20 and 7.40. The response to incremental doses of isoproterenol, a B mimetic agent, was also recorded. Their major finding was a reduction in cardiac contractility at pH 7.20 and a rightward shift of the pH 7.20 curve compared with the 7.40 curve in response to increasing doses of isoproterenol. Therefore, without providing actual new pathophysiological information regarding cardiac depression in acidotic patients, this study definitely confirms the deleterious effects of a moderate and common acidosis on the failing human heart. Obviously, these experimental conditions (that is, ex vivo fragments of myocardium, artificial organic acidosis) are far from the clinical situation. However, this study confirms all other previous results. Furthermore, given that the hemodynamic consequences of common mild acidosis on altered myocardium are important, physicians should be alarmed in the presence of severe acidosis. In shock patients, hemodynamic treatment in order to treat acidosis should be a primary goal for the physician. Finally, it would be of interest, albeit ethically complex, to determine whether this mild acidosis has the same impact not only on preserved human myocardium but also on both preserved and altered arterial vessels.

The management of acidosis remains a complex challenge. The main treatment must involve the correction of the underlying disease at the origin of acidosis. However, buffering severe acidosis by sodium bicarbonate is known to be associated with severe deleterious effects. One such effect is paradoxical intracellular acidosis. Bollaert and colleagues demonstrated that sodium bicarbonate infusion in acidotic rats decreases the intracellular pH [11]. Moreover, sodium bicarbonate infusion increases carbon dioxide, which is highly diffusible in cells (HCO3-+ H+ <=> H2CO3 and H2CO3 <=> CO2 + H2O). Carbon dioxide increases dramatically and exacerbates cardiovascular dysfunction [12]. Another deleterious effect is that hypocalcemia is worsened by bicarbonate infusion, which probably also impairs cardiovascular function [9]. A final example is hydric and sodium overload, which often occurs during sodium bicarbonate infusion.

Two small randomized, controlled clinical studies describe the inefficiency of this treatment in restoring the hemodynamic balance in critically ill patients [9,10]. Other treatments such as Carbicarb, an equimolar solution of sodium bicarbonate and sodium carbonate, or THAM (trometamol; tris-hydroxymethyl aminomethane), a biologically inert amino alcohol of low toxicity that buffers carbon dioxide and acids in vitro and in vivo, have also been studied for the treatment of metabolic or respiratory acidosis, although not in shock state patients [8,13].

For all of these reasons, bicarbonate therapy is not recommended even with pH <7.15. In fact, the Surviving Sepsis Campaign guidelines only recommend against its use for pH ≥7.15 [4]. Currently, there are no relevant published studies regarding the effect of bicarbonate therapy for pH <7.15. Nevertheless, while the underlying disease remains the main course of treatment, there is an urgent need to research a new symptomatic approach to acidosis management.

Competing interests

The authors declare that they have no competing interests.

Schotola H,Toischer K,Popov AF,Renner A,Schmitto JD,Gummert J,Quintel M,Bauer M,Maier LS,Sossalla S,Mild metabolic acidosis impairs the beta-adrenergic response in isolated human failing myocardiumCrit CareYear: 201216R15310.1186/cc1146822889236
Bernard GR,Vincent JL,Laterre PF,LaRosa SP,Dhainaut JF,Lopez-Rodriguez A,Steingrub JS,Garber GE,Helterbrand JD,Ely EW,Fisher CJ Jr,Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study groupEfficacy and safety of recombinant human activated protein C for severe sepsisN Engl J MedYear: 20011669970910.1056/NEJM20010308344100111236773
Ranieri VM,Thompson BT,Barie PS,Dhainaut JF,Douglas IS,Finfer S,Gardlund B,Marshall JC,Rhodes A,Artigas A,Payen D,Tenhunen J,Al-Khalidi HR,Thompson V,Janes J,Macias WL,Vangerow B,Williams MD,Group P-SS,Drotrecogin alfa (activated) in adults with septic shockN Engl J MedYear: 2012162055206410.1056/NEJMoa120229022616830
Dellinger RP,Levy MM,Carlet JM,Bion J,Parker MM,Jaeschke R,Reinhart K,Angus DC,Brun-Buisson C,Beale R,Calandra T,Dhainaut JF,Gerlach H,Harvey M,Marini JJ,Marshall J,Ranieri M,Ramsay G,Sevransky J,Thompson BT,Townsend S,Vender JS,Zimmerman JL,Vincent JL,et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008Crit Care MedYear: 20081629632710.1097/01.CCM.0000298158.12101.4118158437
Lee SW,Hong YS,Park DW,Choi SH,Moon SW,Park JS,Kim JY,Baek KJ,Lactic acidosis not hyperlactatemia as a predictor of in hospital mortality in septic emergency patientsEmerg Med JYear: 20081665966510.1136/emj.2007.05555818843064
Liou YM,Chang JC,Differential pH effect on calcium-induced conformational changes of cardiac troponin C complexed with cardiac and fast skeletal isoforms of troponin I and troponin TJ BiochemYear: 20041668369210.1093/jb/mvh17515632309
Levy B,Collin S,Sennoun N,Ducrocq N,Kimmoun A,Asfar P,Perez P,Meziani F,Vascular hyporesponsiveness to vasopressors in septic shock: from bench to bedsideIntensive Care MedYear: 2010162019202910.1007/s00134-010-2045-820862451
Leung JM,Landow L,Franks M,Soja-Strzepa D,Heard SO,Arieff AI,Mangano DT,Safety and efficacy of intravenous Carbicarb in patients undergoing surgery: comparison with sodium bicarbonate in the treatment of mild metabolic acidosis. SPI Research Group. Study of Perioperative IschemiaCrit Care MedYear: 199416154015497924363
Cooper DJ,Walley KR,Wiggs BR,Russell JA,Bicarbonate does not improve hemodynamics in critically ill patients who have lactic acidosis. a prospective, controlled clinical studyAnn Intern MedYear: 1990164924982156475
Mathieu D,Neviere R,Billard V,Fleyfel M,Wattel F,Effects of bicarbonate therapy on hemodynamics and tissue oxygenation in patients with lactic acidosis: a prospective, controlled clinical studyCrit Care MedYear: 1991161352135610.1097/00003246-199111000-000081935152
Bollaert PE,Robin-Lherbier B,Mallie JP,Nace L,Escanye JM,Larcan A,Effects of sodium bicarbonate on striated muscle metabolism and intracellular pH during endotoxic shockShockYear: 19941619620010.1097/00024382-199403000-000077735951
Berger DS,Fellner SK,Robinson KA,Vlasica K,Godoy IE,Shroff SG,Disparate effects of three types of extracellular acidosis on left ventricular functionAm J PhysiolYear: 1999162 Pt 2H582H5949950860
Nahas GG,Sutin KM,Fermon C,Streat S,Wiklund L,Wahlander S,Yellin P,Brasch H,Kanchuger M,Capan L,Manne J,Helwig H,Gaab M,Pfenninger E,Wetterberg T,Holmdahl M,Turndorf H,Guidelines for the treatment of acidaemia with THAMDrugsYear: 19981619122410.2165/00003495-199855020-000039506241

Article Categories:
  • Commentary

Previous Document:  Pro-anorexia and pro-recovery photo sharing: a tale of two warring tribes.
Next Document:  A descriptive study on health workforce performance after decentralisation of health services in Uga...