Combining central venous-to-arterial partial pressure of carbon dioxide difference and central venous oxygen saturation to guide resuscitation in septic shock

doi:10.1016/j.jcrc.2013.07.049

Journal of Critical Care

Volume 28, Issue 6, December 2013, Pages 1110.e1-1110.e5

https://doi.org/10.1016/j.jcrc.2013.07.049 Get rights and content

Abstract

Purpose

Central venous oxygen saturation (Scvo₂) is a useful therapeutic target when treating septic shock. We hypothesized that combining Scvo₂ and central venous-to-arterial partial pressure of carbon dioxide difference (△ Pco₂) may provide additional information about survival.

Materials and Methods

We performed a retrospective analysis of 172 patients treated for septic shock. All patients were treated using goal-directed therapy to achieve Scvo₂ ≥ 70%. After 6 hours of treatment, we divided patients into 4 groups based on Scvo₂ (< 70% or ≥ 70%) and △ Pco₂ (< 6 mm Hg or ≥ 6 mm Hg).

Results

Overall, 28-day mortality was 35.5%. For patients in whom the Scvo₂ target was not achieved at 6 hours, mortality was 50.0%, compared with 29.5% in those in whom Scvo₂ exceeded 70% (P = .009). In patients with Scvo₂ ≥ 70%, mortality was lower if △ Pco₂ was < 6 mm Hg than if △ Pco₂ was ≥ 6 mm Hg (56.1% vs 16.1%, respectively; P < .001) and 6-hour lactate clearance was superior (0.01 ± 0.61 vs 0.21 ± 0.31, respectively; P = .016).

Conclusions

The combination of Scvo₂ and △ Pco₂ appears to predict outcome in critically ill patients resuscitated from septic shock better than Scvo₂ alone. Patients who meet both targets appear to clear lactate more efficiently.

Introduction

Restoring adequate tissue perfusion and oxygenation are fundamental to achieving good outcomes in patients with shock [1]. Resuscitation may be guided by indicators of tissue hypoxia, such as central venous oxygen saturation (c), which reflects important changes in the relationship between delivery and consumption of oxygen (Do₂/Vo₂). Significant fluctuations in Scvo₂ may occur during sepsis, and high Scvo₂ values do not necessarily reflect changes in cellular oxygen utilization and perfusion of the microcirculation. Persistent tissue hypoperfusion caused by microcirculatory and mitochondrial failure may occur in the presence of normal or increased Scvo₂ [2], which may therefore limit the usefulness of Scvo₂ in clinical practice.

Central or mixed venous–arterial carbon dioxide partial pressure difference (△ Pco₂) has also been used to guide the treatment of shock [3]. △ Pco₂ is the difference between the partial pressure of co₂ in mixed venous blood or central venous blood (Pvco₂ or Pcvco₂) and the partial pressure of co₂ in arterial blood (Paco₂): △ Pco₂ = Pvco₂ – Paco₂. Paco₂ and Pvco₂ represent only a fraction of arterial co₂ content (Caco₂) and central venous co₂ content (Cvco₂), respectively, but as the relationship between partial pressure and content of co₂ is almost linear under normal physiological conditions, Pco₂ can be taken as a measure of Cco₂. At the cellular level, co₂ is a normal terminal product of oxidative metabolism. Thus, in the absence of a shunt, Cco₂ in the effluent venous blood must be higher than in the afferent arterial blood. Therefore, the difference between central venous blood and arterial blood Pco₂ (△ Pco₂) may be considered as a marker of the global hemodynamic status.

The Fick equation applied to co₂ indicates that the co₂ excretion (equivalent to co₂ production in a steady state) equals the product of cardiac output (CO) and the difference between the co₂ content in mixed venous blood (Cvco₂) and in arterial blood (Caco₂): Vco₂ = CO × (Cvco₂–Caco₂). In the equation △ Pco₂ = Vco₂ × k/CO, k is assumed to be constant, and △ Pco₂ is linearly related to co₂ production and inversely related to CO [4]. Therefore, if cardiac output is low, △ Pco₂ is expected to be abnormally high (> 6 mm Hg; [5]).

Critically ill patients with an elevated 6-hour lactate clearance rate have been found to have an improved outcome compared with those with slower lactate clearance [6]. The lactate clearance rate is therefore also clinically useful as an indicator of outcome in severe sepsis and septic shock. The aim of this study was to test the hypothesis that combining Scvo₂ and △ Pco₂ may provide additional information about survival and the ability to clear lactate.

Section snippets

Patients

We retrospectively obtained the data of a series of adults admitted to our 15-bed intensive care unit (ICU) septic shock between January 2010 and December 2012 who were diagnosed with septic shock. The study was approved by the Institutional Ethics Committee, which ruled that as the laboratory tests undertaken and the data collected as part of the study were part of routine clinical practice, informed consent was not required.

Patients are admitted to our ICU from the emergency department, and

Results

Complete follow-up data sets were collected from 172 patients; 110 (64.0%) were men. Their mean age was 61.0 ± 18.7 years and the mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 20.2 ± 9.6 on the first day. Septic shock was caused by pneumonia in 51 patients (29.7%), intra-abdominal abscess in 64 (37.2%), septicemia in 45 (26.2%) and urinary tract infection in two (1.2%); the cause could not be identified in ten patients (5.8%). The influence of goal-directed

Discussion

Septic shock is common and is associated with substantial mortality and substantial consumption of health care resources. The transition from the systemic inflammatory response syndrome to severe sepsis and septic shock involves numerous pathogenic changes, including circulatory abnormalities that result in global tissue hypoxia [10]. The influence of correcting these pathogenic deficiencies has been the focus of many previous studies; in particular, it is well recognized that adopting a

Conclusions

Compared with using Scvo₂ alone, the combination of △ Pco₂ and Scvo₂ may provide additional information about survival and the ability to clear lactate. Elevated △ Pco₂ predicts a worse prognosis and delayed lactate clearance in patients with septic shock and a normal Scvo₂. Prospective randomized trials are needed to examine the pathophysiological mechanisms that underpin our findings. The importance of △ Pco₂ for outcomes might warrant its inclusion as a target in goal-directed treatment

References (15)

W.C. Shoemaker et al.
Role of oxygen debt in the development of organ failure sepsis, and death in high-risk surgical patients
Chest
(1992)
J. Bakker et al.
Veno-arterial carbon dioxide gradient in human septic shock
Chest
(1992)
J. Bakker et al.
Blood lactate levels are superior to oxygen-derived variables in predicting outcome in human septic shock
Chest
(1991)
D. Nichols et al.
Oxygen delivery and consumption: a macrocirculatory perspective
Critical care clinics
(2010)
J.V. Pope et al.
Multicenter study of central venous oxygen saturation (ScvO(2)) as a predictor of mortality in patients with sepsis
Annals of emergency medicine
(2010)
F. Vallee et al.
Central venous-to-arterial carbon dioxide difference: an additional target for goal-directed therapy in septic shock?
Intensive Care Med
(2008)
X. Monnet et al.
Lactate and veno-arterial carbon dioxide difference/arterial-venous oxygen difference ratio, but Not central venous oxygen saturation. Predict increase in oxygen consumption in fluid responders
Crit Care Med
(2013)

There are more references available in the full text version of this article.

Cited by (47)

Pcv-aCO<inf>2</inf> and procalcitonin levels for the early diagnosis of bloodstream infections caused by gram-negative bacteria
2022, American Journal of the Medical Sciences
Citation Excerpt :
This may be due to different pathogen infections cause different circulation disorders,7 and GN bacteria infections are more prone to circulatory failure, leading to poor tissue perfusion.19 As we know, Pcv-aCO2 has been considered an evaluation indicator of tissue perfusion.20 Weil et al. found that Pcv-aCO2 was significantly elevated in patients who underwent cardiac arrest, which is clearly associated with poor tissue perfusion.21
The central venous-to-arterial carbon dioxide difference (Pcv-aCO₂) is a biomarker for tissue perfusion, but the diagnostic value of Pcv-aCO₂ in bacteria bloodstream infections (BSI) caused by gram-negative (GN) bacteria remains unclear. This study evaluated the expression levels and diagnostic value of Pcv-aCO₂ and procalcitonin (PCT) in the early stages of GN bacteria BSI.
Patients with BSI admitted to the intensive care unit at Guangdong Provincial People's Hospital between August 2014 and August 2017 were enrolled. Pcv-aCO₂ and PCT levels were evaluated in GN and gram-positive (GP) bacteria BSI patients.
A total of 132 patients with BSI were enrolled. The Pcv-aCO₂ (8.32 ± 3.59 vs 4.35 ± 2.24 mmHg p = 0.001) and PCT (30.62 ± 34.51 vs 4.92 ± 6.13 ng/ml p = 0.001) levels were significantly higher in the GN group than in the GP group. In the diagnosis of GN bacteria BSI, the area under the receiver operating characteristic curve (AUROC) for Pcv-aCO₂ was 0.823 (95% confidence interval (CI): 0.746–0.900). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 71.90%, 88.00%, 74.07% and 78.21%, respectively. The AUROC for PCT was 0.818 (95% CI: 0.745–0.890). The sensitivity, specificity, PPV and NPV were 57.90%, 94.67%, 71.93% and 74.67%, respectively.
Pcv-aCO₂ and PCT have similar and high diagnostic value for the early diagnosis of BSI caused by GN bacteria.
Acute hyperventilation increases oxygen consumption and decreases peripheral tissue perfusion in critically ill patients
2021, Journal of Critical Care
Citation Excerpt :
Similarly, mixed venous PaCO2 and central venous PaCO2 was taken samples at different locations, so the results are different and the comparison may be controversial. However, there are many literatures shows that the central venous Pv-aCO2 could also reflect the relationship between DO2 and VO2 and guide the resuscitation of shock [3,40]. Third, although only 54 patients were evaluated, this is still the largest among similar studies [8,17,18].
This study aimed to evaluate the effects of acute hyperventilation on central venous-to-arterial carbon dioxide tension difference (Pv-aCO₂), central venous oxygen saturation (ScvO₂), central venous-to-arterial CO₂ difference/arterial-central venous O₂ difference ratio (CO₂GAP-Ratio), and peripheral perfusion index (PI) in hemodynamically stable critically ill patients.
Fifty-four mechanically ventilated patients were evaluated. The cardiac index, Pv-aCO₂, ScvO₂, CO₂GAP-Ratio, PI, and arterial and venous blood gas parameters were measured in the first set of measurements. Then, alveolar ventilation was increased by raising the respiratory rate (10 breaths/min). After a 30 min hyperventilation period, the second set of measurements was recorded.
Acute hyperventilation induces an increase in Pv-aCO₂ (from 3.87 ± 1.31 to 8.44 ± 1.81 mmHg, P < 0.001) and a decrease in ScvO₂(from 71.78 ± 4.82 to 66.47 ± 5.74%, P < 0.001). The CO₂GAP-Ratio was significantly increased(from 0.97 ± 0.40 to 1.74 ± 0.46, P < 0.001), and the PI showed a remarkable decrease caused by acute hyperventilation(from 1.82 ± 1.14 to 1.40 ± 0.99，P = 0.04). Hyperventilation-induced ∆_Pv-aCO₂ was negatively correlated with ∆PaCO₂(r = −0.572, P<0.001). The change in ∆_PaCO₂ was correlated with ∆_ScvO₂(r = 0.450, P<0.001). However, the left ventricular outflow tract velocity time integral (LVOT-VTI) remained unchanged during hyperventilation.
Acute hyperventilation induced an increase in oxygen consumption and decreased peripheral tissue perfusion in patients. For critical care patients, it is necessary to pay attention to the influence of hyperventilation on peripheral tissue perfusion indices and oxygen consumption indices.
P(v-a)CO2/C(a-v)O2-directed resuscitation does not improve prognosis compared with SvO2 in severe sepsis and septic shock: A prospective multicenter randomized controlled clinical study
2018, Journal of Critical Care
Citation Excerpt :
We used P(v-a)CO2 instead of C(v − a)CO2 in the formula, but the relationship between P(v-a)CO2 and C(v − a)CO2 is not always linear and depends on pH and hemoglobin saturation. Ospina-Tascon et al. [23] confirmed that C(v − a)CO2/C(a-v)O2, but not P(v-a)CO2/C(a-v)O2, was an independent predictor of mortality at day 28. Therefore, C(v − a)CO2/C(a-v)O2-directed therapy may be more accurate.
The present study examined the value of P(v-a)CO2/C(a-v)O2 compared with ScvO2 as a target for clinical resuscitation of severe sepsis/septic shock.
228 patients were randomly divided into a P(v-a)CO2/C(a-v)O2-targeted and a ScvO2-targeted therapy group. The effects on hemodynamics, interventional intensity, and outcome were recorded and analyzed.
The mean arterial pressure (MAP) of the P(v-a)CO2/C(a-v)O2-targeted therapy group was significantly higher at 3 h, 12 h, 24 h, and 3 days (P < .05). The P(v-a)CO2/C(a-v)O2 of the ScvO2-targeted therapy group was significantly higher at each time point after resuscitation (P < .05). However, the CVP, lactate, urine output, ScvO2, and P(v-a)CO2 were not significantly improved. The P(v-a)CO2/C(a-v)O2-targeted therapy group used a smaller fluid volume and required fewer red blood cell transfusions and vasoactive drugs, but these results were also not significant. There were no differences between 28-day and 60-day mortality, APACHEII and SOFA scores, ICU length of stay, residence length of stay, number of days free of vasoactive drugs, or number of ventilator-free days. Post hoc tests revealed no significant differences between these two groups in 28-day survival.
P(v-a)CO2/C(a-v)O2-directed resuscitation did not improve prognosis compared with ScvO2 in severe sepsis and septic shock.
ClinicalTrials.gov Identifier NCT01877798
Early fluid loading for septic patients: Any safety limit needed?
2018, Chinese Journal of Traumatology - English Edition
Early adequate fluid loading was the corner stone of hemodynamic optimization for sepsis and septic shock. Meanwhile, recent recommended protocol for fluid resuscitation was increasingly debated on hemodynamic stability vs risk of overloading. In recent publications, it was found that a priority was often given to hemodynamic stability rather than organ function alternation in the early fluid resuscitation of sepsis. However, no safety limits were used at all in most of these reports. In this article, the rationality and safety of early aggressive fluid loading for septic patients were discussed. It was concluded that early aggressive fluid loading improved hemodynamics transitorily, but was probably traded off with a follow-up organ function impairment, such as worsening oxygenation by reduction of lung aeration, in a part of septic patients at least. Thus, a safeguard is needed against unnecessary excessive fluids in early aggressive fluid loading for septic patients.
The Evolution of Central Venous-to-arterial Carbon Dioxide Difference (PCO<inf>2</inf> Gap) during Resuscitation Affects ICU Outcomes: A Prospective Observational Study
2024, Indian Journal of Critical Care Medicine
A review of using CO<inf>2</inf>-derived variables to detect tissue hypoperfusion during cardiopulmonary bypass
2024, Perfusion (United Kingdom)

View all citing articles on Scopus

^☆: The authors declare that they have no conflict of interest.

View full text

Electronic ArticleCombining central venous-to-arterial partial pressure of carbon dioxide difference and central venous oxygen saturation to guide resuscitation in septic shock☆

Abstract

Purpose

Materials and Methods

Results

Conclusions

Introduction

Section snippets

Patients

Results

Discussion

Conclusions

Chest

Chest

Chest

Critical care clinics

Multicenter study of central venous oxygen saturation (ScvO(2)) as a predictor of mortality in patients with sepsis

Annals of emergency medicine

Central venous-to-arterial carbon dioxide difference: an additional target for goal-directed therapy in septic shock?

Intensive Care Med

Lactate and veno-arterial carbon dioxide difference/arterial-venous oxygen difference ratio, but Not central venous oxygen saturation. Predict increase in oxygen consumption in fluid responders

Crit Care Med

Electronic Article
Combining central venous-to-arterial partial pressure of carbon dioxide difference and central venous oxygen saturation to guide resuscitation in septic shock☆