Document Detail

A large Venous-Arterial PCO(2) Is Associated with Poor Outcomes in Surgical Patients.
Jump to Full Text
MedLine Citation:
PMID:  22007204     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Background. This study evaluated whether large venous-arterial CO(2) gap (PCO(2) gap) preoperatively is associated to poor outcome. Method. Prospective study which included adult high-risk surgical patients. The patients were pooled into two groups: wide [P(v-a)CO(2)] versus narrow [P(v-a)CO(2)]. In order to determine the best value to discriminate hospital mortality, it was applied a ROC (receiver operating characteristic) curve for the [P(v-a)CO(2)] values collected preoperatively, and the most accurate value was chosen as cut-off to define the groups. Results. The study included 66 patients. The [P(v-a)CO(2)] value preoperatively that best discriminated hospital mortality was 5.0 mmHg, area = 0.73. Preoperative patients with [P(v-a)CO(2)] more than 5.0 mmHg presented a higher hospital mortality (36.4% versus 4.5% P = 0.004), higher prevalence of circulatory shock (56.8% versus 22.7% P = 0.01) and acute renal failure postoperatively (27.3% versus 4.5% P = 0.02), and longer hospital length of stays 20.0 (14.0-30.0) versus 13.5 (9.0-25.0) days P = 0.01. Conclusions. The PCO(2) gap values more than 5.0 mmHg preoperatively were associated with worse postoperatively outcome.
Authors:
João M Silva; Amanda M Ribas R Oliveira; Juliano Lopes Segura; Marcel Henrique Ribeiro; Carolina Nacevicius Sposito; Diogo O Toledo; Ederlon Rezende; Luiz M Sá Malbouisson
Related Documents :
21833684 - Shoulder adhesive capsulitis: manipulation and arthroscopic arthrolysis or intra-articu...
22205554 - Comparison of the effects of different intravenous fat emulsions in patients with syste...
6165754 - Long-term results of dorsal stabilization in the rheumatoid wrist.
21714794 - Development of a refractory gastro-oesophageal reflux score using an administrative cla...
7517304 - Transverse keratotomy combined with spherical photorefractive keratectomy for compound ...
22157324 - Systemic antibiotic therapy for chronic osteomyelitis in adults.
Publication Detail:
Type:  Journal Article     Date:  2011-10-05
Journal Detail:
Title:  Anesthesiology research and practice     Volume:  2011     ISSN:  1687-6970     ISO Abbreviation:  Anesthesiol Res Pract     Publication Date:  2011  
Date Detail:
Created Date:  2011-10-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101532982     Medline TA:  Anesthesiol Res Pract     Country:  United States    
Other Details:
Languages:  eng     Pagination:  759792     Citation Subset:  -    
Affiliation:
Anestesiologia e Cuidados Intensivos, Hospital do Servidor Público Estadual, 04039-901 São Paulo, SP, Brazil.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

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

Full Text
Journal Information
Journal ID (nlm-ta): Anesthesiol Res Pract
Journal ID (publisher-id): ARP
ISSN: 1687-6962
ISSN: 1687-6970
Publisher: Hindawi Publishing Corporation
Article Information
Download PDF
Copyright © 2011 João M. Silva Jr. et al.
open-access:
Received Day: 23 Month: 5 Year: 2011
Revision Received Day: 31 Month: 7 Year: 2011
Accepted Day: 4 Month: 8 Year: 2011
Print publication date: Year: 2011
Electronic publication date: Day: 5 Month: 10 Year: 2011
Volume: 2011E-location ID: 759792
ID: 3189458
PubMed Id: 22007204
DOI: 10.1155/2011/759792

A large Venous-Arterial PCO2 Is Associated with Poor Outcomes in Surgical Patients
João M. Silva, Jr.1*
Amanda M. Ribas R. Oliveira2
Juliano Lopes Segura3
Marcel Henrique Ribeiro3
Carolina Nacevicius Sposito3
Diogo O. Toledo2
Ederlon Rezende2
Luiz M. Sá Malbouisson4
1Anestesiologia e Cuidados Intensivos, Hospital do Servidor Público Estadual, 04039-901 São Paulo, SP, Brazil
2De Terapia Intensiva, Hospital do Servidor Público Estadual, 04039-901 São Paulo, SP, Brazil
3Anestesiologia, Hospital do Servidor Público Estadual, 04039-901 São Paulo, SP, Brazil
4De Terapia Intensiva, Hospital das Clínicas, 05403-900 São Paulo, SP, Brazil
Correspondence: *João M. Silva Jr.: joao.s@globo.com
[other] Academic Editor: William McBride

1. Introduction

Although every year millions of surgeries are performed all around the world, few patients that undergo major surgeries are judged to be of high risk for postoperative complications and death [1]. An observational study reported that only 12.5% of all surgical procedures are considered high risk, but over 80% of the deaths which occurred were in the high-risk group [1]. Despite the high mortality rate, less than 15% of those patients are admitted to intensive care units (ICU) [1], which shows that the individual risk may easily be underestimated and that high-risk patients may not be recognized.

The mechanisms by which inflammatory response and tissue hypoperfusion occur in major surgery are still not entirely clear, but evidence indicates that oxygen requirements increase significantly as a result of the injury and metabolic response to the trauma caused by the surgery. However, very often high-risk patients are not able to increase their cardiac output and thus the oxygen delivery [2]. Therefore, those patients will more likely develop tissue hypoperfusion and severe systemic inflammatory response and death due to the organ dysfunction [3].

Surgical patients with a high risk for complications admitted to an ICU frequently die as a primary or secondary consequence of hypoperfusion-related organ dysfunction or severe infections [4, 5]. However, predictors of death caused by tissue hypoperfusion are still not studied very much in high-risk surgery patients. The [P(v-a)CO2] has been reversely correlated to cardiac output in surgical patients [68]. In a recent review, Lamia et al. [9] showed that PCO2 gap is a blood flow marker to remove total CO2 produced by the peripheral tissue. Cuschieri et al. [10] have found a reverse correlation between [P(cv-a)CO2] and cardiac index with a central venous blood sample and suggested that, for this purpose, a sample of central venous blood could be used instead of blood from the pulmonary artery.

In the literature, we find only very few prospective clinical studies with surgical patients, which have evaluated the real impact from [P(v-a)CO2] as complications and death preoperative marker in this population. Therefore, the objective of this study was to evaluate the role of PCO2 gap as a predictor for complications and death in high-risk surgical patients.


2. Methods

The study was performed in a tertiary hospital. It was approved by the local Ethics and Research Committees, and a written postinformed consent was obtained from each patient or legal responsible. The study design was a post hoc analysis applying a cut point derived from the data, with the following inclusion criteria: (1) patients aged 18 years or older and (2) surgeries which required a central venous catheter in intraoperative and intensive care in postoperative phase. Patients were selected during the preanesthetic evaluation. High-risk surgeries were patients undergoing surgeries with requested ICU postoperative stay and at least one of the following:

  1. severe cardiorespiratory comorbidities (coronary insufficiency, chronic obstructive pulmonary disease, previous stroke),
  2. surgery scheduled for neoplasm resection (esophagectomy, total gastrectomy) longer than 8 hours,
  3. above 70 years-old, with evidence of physiological reserve impairment involving at least one vital organ,
  4. acute renal failure (blood urea nitrogen > 100 mg/dL or creatinine > 3 mg/dL),
  5. advanced vascular disease, or aortal involvement,
  6. massive acute intraoperative blood loss predicted,
  7. severe nutritional disorders patients.

Patients undergoing palliative surgery, with low life expectancy, liver failure (Child B or C), patients with a functional class IV heart failure or an echocardiogram-measured ejection fraction of less than 30%, and those who did not accept participating in the study were excluded. The patients with a functional class IV heart failure or ejection fraction of less than 30% could present flow alteration due to underlying disease, which is not related to surgery procedure.

At the time of the inclusion, the Multiple-Organ Dysfunction Syndrome (MODS) [11] and Acute Physiology And Chronic Health Evaluation (APACHE II) [12] scores were also evaluated by taking the worst values of their variables. An echocardiogram, which is an integral part of preoperative evaluation of high-risk surgical patients in our institution, was performed to measure the ejection fraction and the presence or absence of systolic or diastolic ventricular dysfunction, considering the increasingly clear literature data on their similarities regarding mortality and morbidity [1316].

At the day of the surgery, patients were equipped with central venous (positioned with the tip within the superior vena cava) and arterial catheters. A chest X-ray confirmed central venous catheter position. Before anesthesia induction, in intraoperatively and postoperatively central venous and arterial blood samples were collected to measure [P(v-a)CO2].

The surgical team decided on which therapy should be used during the intraoperative period. In the postoperative phase, the intensive care physician's goal was to improve the perfusion parameters according to standard in local institution; he had no knowledge about preoperative [P(v-a)CO2].

The primary endpoint was hospital mortality; all patients were therefore monitored until they were discharged from hospital. The secondary endpoint was to check for the presence of an organ dysfunction, shock (need of vasoactive drugs for over 1 hour, despite volemic resuscitation), acute pulmonary dysfunction (PaO2/FiO2 ratio < 200), renal failure (increase of creatinine by 50% or urinary output of less than 400 mL in 24 hours), confusion (change in behavior, memory lapses, or psychomotor agitation), and platelet dysfunction (platelets reduced by 30% compared to the basal value) in up to 24 hours in the postoperative period. Diagnosis of postoperative infection was based on international consensus guidelines and/or use of antibiotic [17]. The infections incidence during ICU length of stay and the time of mechanical ventilation were verified, besides the hospital length of stay.

Based on the best [P(v-a)CO2] value which discriminated hospital mortality, the patients were allocated in two groups: narrow [P(v-a)CO2] (group 1) and wide [P(v-a)CO2] (group 2).

2.1. Statistical Analysis

Initially, we described the demographic, clinical, and physiological characteristics from patients that were included in the study. Frequencies were calculated to describe categorical variables. Quantitative variables were described by using measures of central tendency and dispersion.

The statistical method to be used in the assessment of each variable was chosen based on its distribution. Categorical variables were analyzed through the Chi-square test, and continuous variables through the mean with the Student's t-test for normal distribution and continuous variables with irregular distribution were analyzed by means of the Mann-Whitney Test. P  values < 0.05 (two-tailed) were considered significant. ROC curves were used to test the discrimination power of the groups in predicting clinical evolution (the capacity of correctly classifying survivors and nonsurvivors) and to determine the best cut-off value of tissue perfusion in connection with hospital mortality. SPSS 13.0 was used to analyze those calculations. Group 01 patients were compared to those of group 02. Box plots were created to compare survivors and nonsurvivors in [P(v-a)CO2] in different time points through Mann-Whitney test.

To determine the risk of hospital death we developed a multivariable Cox proportional hazard model in the population. Variables were included in the model if they reached a significance level of P < 0.05 in univariate analysis or were clinically relevant. Mortality estimative curve was created using the Cox method and compared by Cox regression.


3. Results

Over a period of 6 months, the study included 66 patients, of which 37 males and 29 females, with an average age of 65.6 years old. Elective surgeries were more frequent (Table 1).

During surgery, 50% of patients received blood transfusions, 32.5% vasoactive drugs, and 54.5% of them had complications, where circulatory shock was most prevalent (Table 2).

A ROC curve was created in order to establish the best [P(v-a)CO2] value, which discriminated hospital mortality in this population, where [P(v-a)CO2] = 5.0 mmHg was the cut-off between narrow [P(v-a)CO2] and wide [P(v-a)CO2], presenting sensitivity of 93.3% and specificity of 50.2%, ROC area of 0.73, P(area = 0.5) = 0.0006, 95% CI = 0.61 to 0.84 (Figure 1). Moreover, comparative ROC curves from lactate, BE and ScvO2 can demonstrate that [P(v-a)CO2] had the greatest AUC, respectively, 0.53 (0.41 to 0.67), 0.56 (0.43 to 0.69), and 0.71 (0.59 to 0.82).

A Box plot graphic has compared survivors and non survivors in pre-, intra-, and postoperatively; it could show that only the preoperatively period presented statistical significance between them (Figure 2).

Thus, when comparing the groups with narrow [P(v-a)CO2] and wide [P(v-a)CO2], although they present the same pre- and intraoperative demographic and clinical data, except for a lower ScvO2 and a higher ventricular dysfunction in patients with [P(v-a)CO2] ≥ 5.0 mmHg, we find that patients with [P(v-a)CO2] ≥ 5.0 mmHg had a higher hospital mortality and a higher incidence of complications in the postoperative period, mainly circulatory shock, renal failure, and ICU infection. (Tables 1, 2, 3, and 4)

When patients with [P(v-a)CO2] < 5.0 mmHg and [P(v-a)CO2] ≥ 5.0 mmHg were compared, the group with [P(v-a)CO2] ≥ 5.0 mmHg had a lower survival probability, even when it was adjusted by MODS, ScvO2, ventricular dysfunction heart. HR = 2.07 IC95% 1.14–3.77 (Figure 3).


4. Discussion

Despite the large quantity of resources that are directed towards assessing perioperative risk and of cardiovascular complications, this study shows that a simple analysis of PCO2 gap ≥ 5.0 mmHg in the preoperative period is an important marker for postoperative complications, mainly shock, renal failure, infection, increased length hospital stay, and hospital mortality. Currently, few parameters are used at bed side to assess tissue hypoxia, such as urinary output, base differences, and blood lactate, but those parameters show that hypoperfusion is already installed and may be late to guide the onset of a hemodynamic resuscitation [18]. However, in this study, [P(v-a)CO2] has proven to be an early parameter to identify worse outcome in surgery patients.

The worse outcome of these patients can be explained by previous reports that have suggested the PCO2 gap as a marker for tissue hypoxia [19, 20]. In an animal model for acute hemorrhage, Van der Linden et al. [21] found a significant correlation between blood lactate and PCO2 gap. A progressive increase of [P(v-a)CO2] was observed during the dependence period of oxygen consumption and delivery (VO2/DO2) in another experimental model with progressive flow reduction [22]. High [P(v-a)CO2] values have been reported during cardiac arrest and cardiopulmonary resuscitation [19, 23]. However, in all those studies, tissue hypoxia was secondary to the reduction of blood flow.

Circulatory failure is followed by tissue CO2 accumulation. Tissue CO2 increases as a consequence of an accumulation of the carbon dioxide produced by the aerobic metabolism and by the tissue bicarbonate buffer effect, which is necessary to correct the excess of hydrogen ions during the anaerobic metabolism. When the cell concentration of bicarbonate ion (HCO3) and hydrogen ion (H+) rises, HCO3 diffuses out of red blood cells into the plasma, but H+ cannot diffuse easily because the cell membrane is relatively impermeable to cations. Some of H+ liberated are bound to hemoglobin (Hb). This reaction occurs because reduced Hb is a better acceptor of H+ than the oxygenated Hb. In the peripheral blood the loading of CO2 is facilitated by the presence of reduced Hb (Haldane effect) [9].

Low blood flow can result in tissue hypercapnia. Under anaerobic metabolism conditions, it is expected that the production of CO2 (VCO2) decreases less than the consumption of O2 (VO2). In other words, the VCO2/VO2 ratio (respiratory quotient) should increase. According to the Fick equation, a low blood flow may result in an increase of [P(v-a)CO2], even without any additional production of CO2. This can be explained by the CO2-stagnation phenomenon [24] due to the slower microcirculation blood flow, which is larger than normal CO2 production; hypercapnia tends to be generated in the venous circulation.

Therefore, [P(v-a)CO2] is proportional to CO2 production and inversely related to cardiac output (Fick equation). Anaerobic CO2 production occurs when tissue hypoxia is present, mainly to protect bicarbonate ions against excess protons, produced as a secondary consequence of adenosine triphosphate hydrolysis [25].

In this respect, an increased [P(v-a)CO2] value has been reported in patients with low cardiac output and no global tissue hypoxia, as demonstrated by the normal lactate levels that were found [26]. This emphasizes the lack of specificity of [P(v-a)CO2] in detecting tissue hypoxia. In this study, we observed that even patients with inadequate [P(v-a)CO2] values presented normal lactate or base difference values. Serum lactate has been traditionally accepted like an indicator of anaerobic metabolism and of tissue hypoxia, but it has to be emphasized that, under normal conditions, the liver is capable of increasing the metabolism of the produced lactate; this means that, in hypoxia and anaerobic metabolism situations, a few hours may elapse between the onset of the phenomenon and the detection of elevated lactate levels in the blood [27], which explains why the lactate may not be as early as of the [P(v-a)CO2].

Otherwise, a normal [P(v-a)CO2] value may be associated with global tissue hypoxia in normal or hyperdynamic states, which was demonstrated by some authors [28]. This fact explains why an elevated venous flow is sufficient to clear the CO2 that is produced by the hypoxic cell, even if the production of CO2 is higher than normal due to the anaerobiosis that generates CO2 [24]. Indeed, Vallet and colleagues evidenced that PCO2 gap increased during low blood flow-induced tissue hypoxia (ischemic hypoxia) while it remained unchanged during hypoxemia-induced hypoxia (hypoxic hypoxia) [29]. We emphasize once again the poor sensitivity of [P(v-a)CO2] to detect tissue hypoxia in some cases. However, in this study, patients with an inadequate [P(v-a)CO2] had a lower ScvO2, which may be explained by the fact that ScvO2 is influenced by different variables [30], such as low blood flow; this might be occurring with the sample in question. This hypothesis is substantiated by a higher percentage of ventricular dysfunction in this group.

The prevalence of ventricular dysfunction in this study was evaluated, considering both the systolic and diastolic ventricular dysfunction, since their evolution as for morbidity and mortality is similar [1316]. A greater prevalence of ventricular dysfunction was found in the inadequate [P(v-a)CO2] group. The EF—close to 65% in both groups—reflects a predominant diastolic dysfunction, which substantiates current data, which present diastolic dysfunction as a more relevant prognosis predictor than EF per se. [3134].

However, Vallée et al. [35] found that a ScvO2 of over 70% in septic patients was not enough to reach adequate resuscitation, and that [P(v-a)CO2] ≥6.0 mmHg could be helpful to identify patients that were not adequately resuscitated. Mekontso-Dessap et al. [24] demonstrated that, under conditions of tissue hypoperfusion, defined as a blood lactate level of >2.0 mmol/L, a PvCO2-PaCO2/Ca-vO2 ratio of >1.4 was the best predictor of hyperlactatemia and a good prognostic index.

Thus, it is important to detect early a risk factor for low oxygen delivery due to low blood flow evaluated by PCO2 gap ≥5.0 mmHg in surgery patients, because changes in clinical management may be made in order to avoid an unfavorable outcome in this population. Several clinical studies have documented that and aggressive early resuscitation using defined protocols improve the patient's outcome [36, 37]. These studies used therapy strategies to increase the cardiac function and keep organ perfusion, which reduced the ICU length of stay, accelerated the recovery of the gastrointestinal function, and reduced the mortality rate in high-risk surgery patients [38]. Therefore, [P(v-a)CO2] could help identify patients that require such optimizations in the preoperative phase and specific measures taken in the preoperative or intraoperative period to ensure that the increase of blood flow could bring benefits to the postoperative period and improve the prognosis.

However, in this study, the [P(v-a)CO2] value that best discriminated mortality was lower than of those described previously in the literature. This can be probably explained by the fact that those studies discussed more severe patients with septic conditions that required high oxygen delivery, contrary to what was shown in the study in question, since their patients were in the preoperative period of elective surgeries, with low APACHE II values, most of them in ASA II physical condition. In addition, values of the inadequate [P(v-a)CO2] found in this evaluation may eventually mean that the patients were not well enough to undergo major surgeries, but tolerable for basal activities, which are not comparable to the stress experienced in a surgical procedure.

Another aspect that has to be discussed is related to the fact that inadequate [P(v-a)CO2] was found only in the preoperative and not in the intraoperative phase; it is important to highlight that in the intraoperative period some variables may interfere in the measurement of [P(v-a)CO2], such as the anesthesia and hypothermia that might occur during surgery; they may reduce cell respiration and, thus, CO2 production. Hypothermia reduces metabolism by 7% per grade, with reduction of ATP formation and reduction of cellular oxygen and cerebral glucose requirements, in addition, decrease in CO2 production and O2 consumption [39].

Other aspects can bring impact to change in [P(v-a)CO2], due to CO2 dissociation curve, which is curvilinear more than oxygen dissociation curve, and temperature, hematocrit, oxygen saturation, and pH influence the PCO2/CO2 content relationship an example is showed when metabolic acidosis worsens; the relationship is shifted to the right; it means that the same CO2 content value can determinate superior PCO2 value [9].

Besides, although in most studies that evaluated [P(v-a)CO2] patients were monitored by means of a pulmonary artery catheter [24], absence of this tool in this study does not limit the results that were found. By the other hand, the gastric tonometry has also been utilized as carbon dioxide monitoring [40], but this method assesses the regional tissue dysoxia, differently of the proposal from present study which has aimed to measure the systemically problem. Therefore, since the study's objective does not require the measures that are evaluated by these devices, this way can be cheaper.

The complications, except infection, were evaluated in 24 hours only, which makes a limitation, but the length of ICU stay of all patients was short, that is, median 3.0 days.

The sample sizes as well as the observational character of this study are limiting factors. Future researches are needed to validate this finding.

Therefore, patients who underwent major surgeries and that—in the preoperative period—presented a PCO2 gap ≥5 mmHg had a worse prognosis in the postoperative. This marker may turn out to be important to stratify risk and suggests a useful additional tool for perioperative management.


Conflict of Interests

The authors declare that there is no conflict of interests.


Authors' Contribution

J. M. S. Jr. conceived of this study, participated in the design of the study, performed the statistical analysis, and drafted the paper. A. M. R. R. Oliveira participated in the design of the study, performed the collection of data and the statistical analysis, and drafted the paper. J. L. Segura, M. H. Ribeiro, and C. N. Sposito performed the collection of data. D. O. Toledo, E. Rezende, and L. M. S. Malbouisson helped in revising of the draft, the paper and helped in the final revision of writing the paper. All authors read and approved the final paper.


References
1. Jhanji S,Thomas B,Ely A,Watson D,Hinds CJ,Pearse RM. Mortality and utilisation of critical care resources amongst high-risk surgical patients in a large NHS trustAnaesthesiaYear: 200863769570018489613
2. Shoemaker WC,Appel PL,Kram HB,Waxman K,Lee TS. Prospective trial of supranormal values of survivors as therapeutic goals in high-risk surgical patientsChestYear: 1988946117611863191758
3. Older P,Smith R,Courtney P,Hone R. Preoperative evaluation of cardiac failure and ischemia in elderly patients by cardiopulmonary exercise testingChestYear: 199310437017048365279
4. Mayr VD,Dünser MW,Greil V,et al. Causes of death and determinants of outcome in critically ill patientsCritical CareYear: 2006106, 154
5. Tran DD,Groeneveld AB,van der Meulen J,Nauta JJ,van Schijndel RJS,Thijs LG. Age, chronic disease, sepsis, organ system failure, and mortality in a medical intensive care unitCritical Care MedicineYear: 19901854744792328591
6. Groeneveld AB,Vermeij CG,Thijs LG. Arterial and mixed venous blood acid-base balance during hypoperfusion with incremental positive end-expiratory pressure in the pigAnesthesia and AnalgesiaYear: 19917355765821952138
7. Durkin R,Gergits MA,Reed JF III,Fitzgibbons J. The relationship between the arteriovenous carbon dioxide gradient and cardiac indexJournal of Critical CareYear: 1993842172218305959
8. Brandi LS,Giunta F,Pieri M,Sironi AM,Mazzanti T. Venous-arterial PCO2 and pH gradients in acutely ill postsurgical patientsMinerva AnestesiologicaYear: 19956193453508919829
9. Lamia B,Monnet X,Teboul JL. Meaning of arterio-venous PCO2 difference in circulatory shockMinerva AnestesiologicaYear: 200672659760416682934
10. Cuschieri J,Rivers EP,Donnino MW,et al. Central venous-arterial carbon dioxide difference as an indicator of cardiac indexIntensive Care MedicineYear: 200531681882215803301
11. Marshall JC,Cook DJ,Christou NV,Bernard GR,Sprung CL,Sibbald WJ. Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcomeCritical Care MedicineYear: 19952310163816527587228
12. Knaus WA,Draper EA,Wagner DP,Zimmerman JE. APACHE II: a severity of disease classification systemCritical Care MedicineYear: 198513108188293928249
13. Tsutsui H,Tsuchihashi-Makaya M,Kinugawa S. Clinical characteristics and outcomes of heart failure with preserved ejection fraction: lessons from epidemiological studiesJournal of CardiologyYear: 2010551132220122544
14. Bhatia RS,Tu JV,Lee DS,et al. Outcome of heart failure with preserved ejection fraction in a population-based studyNew England Journal of MedicineYear: 2006355326026916855266
15. Fonarow GC,Stough WG,Abraham WT,et al. Characteristics, treatments, and outcomes of patients with preserved systolic function hospitalized for heart failure: a report from the OPTIMIZE-HF registryJournal of the American College of CardiologyYear: 200750876877717707182
16. Tsuchihashi-Makaya M,Hamaguchi S,Kinugawa S,et al. Characteristics and outcomes of hospitalized patients with heart failure and reduced vs preserved ejection fraction. Report from the Japanese cardiac registry of heart failure in cardiology (JCARE-CARD)Circulation JournalYear: 200973101893190019644216
17. Levy MM,Fink MP,Marshall JC,et al. 2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conferenceCritical Care MedicineYear: 20033141250125612682500
18. Rezende E,Silva JM Jr.,Isola AM,Campos EV,Amendola CP,Almeida SL. Epidemiology of severe sepsis in the emergency department and difficulties in the initial assistanceClinicsYear: 200863445746418719755
19. Weil MH,Rackow EC,Trevino R,Grundler W,Falk JL,Griffel MI. Difference in acid-base state between venous and arterial blood during cardiopulmonary resuscitationNew England Journal of MedicineYear: 198631531531563088448
20. Johnson BA,Weil MH. Redefining ischemia due to circulatory failure as dual defects of oxygen deficits and of carbon dioxide excessesCritical Care MedicineYear: 19911911143214381935165
21. van der Linden P,Rausin I,Deltell A,et al. Detection of tissue hypoxia by arteriovenous gradient for PCO2 and pH in anesthetized dogs during progressive hemorrhageAnesthesia and AnalgesiaYear: 19958022692757818112
22. Zhang H,Vincent JL. Arteriovenous differences in PCO2 and pH are good indicators of critical hypoperfusionAmerican Review of Respiratory DiseaseYear: 199314848678718214940
23. Adrogue HJ,Rashad MN,Gorin AB,Yacoub J,Madias NE. Assessing acid-base status in circulatory failure. Differences between arterial and central venous bloodNew England Journal of MedicineYear: 198932020131213162535633
24. Mekontso-Dessap A,Castelain V,Anguel N,et al. Combination of venoarterial PCO2 difference with arteriovenous O2 content difference to detect anaerobic metabolism in patientsIntensive Care MedicineYear: 200228327227711904655
25. Randall HM Jr.,Cohen JJ. Anaerobic CO2 production by dog kidney in vitroThe American Journal of PhysiologyYear: 196621124935054288380
26. Teboul JL,Mercat A,Lenique F,Berton C,Richard C. Value of the venous-arterial Pco2 gradient to reflect the oxygen supply to demand in humans: effects of dobutamineCritical Care MedicineYear: 1998266100710109635647
27. Nguyen HB,Rivers EP,Knoblich BP,et al. Early lactate clearance is associated with improved outcome in severe sepsis and septic shockCritical Care MedicineYear: 20043281637164215286537
28. Bakker J,Vincent JL,Gris P,Leon M,Coffernils M,Kahn RJ. Veno-arterial carbon dioxide gradient in human septic shockChestYear: 199210125095151735281
29. Vallet B,Teboul JL,Cain S,Curtis S. Venoarterial CO(2) difference during regional ischemic or hypoxic hypoxiaJournal of Applied PhysiologyYear: 20008941317132111007564
30. Silva JM Jr.,Toledo DO,Magalhães DD,et al. Influence of tissue perfusion on the outcome of surgical patients who need blood transfusionJournal of Critical CareYear: 200924342643419327957
31. Little WC,Oh JK. Echocardiographic evaluation of diastolic function can be used to guide clinical careCirculationYear: 2009120980280919720946
32. Nagueh SF,Appleton CP,Gillebert TC,et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiographyJournal of the American Society of EchocardiographyYear: 200922210713319187853
33. Brucks S,Little WC,Chao T,et al. Relation of anemia to diastolic heart failure and the effect on outcomeAmerican Journal of CardiologyYear: 20049381055105715081458
34. Sturgess DJ,Marwick TH,Joyce C,et al. Prediction of hospital outcome in septic shock: a prospective comparison of tissue Doppler and cardiac biomarkersCritical CareYear: 2010142p. R44
35. Vallée F,Vallet B,Mathe O,et al. Central venous-to-arterial carbon dioxide difference: an additional target for goal-directed therapy in septic shock?Intensive Care MedicineYear: 200834122218222518607565
36. Fenwick E,Wilson J,Sculpher M,Claxton K. Pre-operative optimisation employing dopexamine or adrenaline for patients undergoing major elective surgery: a cost-effectiveness analysisIntensive Care MedicineYear: 200228559960812029409
37. Mythen MG,Webb AR. Perioperative plasma volume expansion reduces the incidence of gut mucosal hypoperfusion during cardiac surgeryArchives of SurgeryYear: 199513044234297535996
38. Kern JW,Shoemaker WC. Meta-analysis of hemodynamic optimization in high-risk patientsCritical Care MedicineYear: 20023081686169212163777
39. Aslami H,Juffermans NP. Induction of a hypometabolic state during critical illness—a new concept in the ICU?Netherlands Journal of MedicineYear: 201068519019820508267
40. Marik PE. Regional carbon dioxide monitoring to assess the adequacy of tissue perfusionCurrent Opinion in Critical CareYear: 200511324525115928474

Article Categories:
  • Clinical Study


Previous Document:  Sense and nonsense of an extended pelvic lymph node dissection in prostate cancer.
Next Document:  Spinal cord stimulation: the clinical application of new technology.