Central Venous Pressure Value Can Assist in Adjusting Norepinephrine Dosage After the Initial Resuscitation of Septic Shock

0
0
0

Central Venous Pressure Value Can Assist in Adjusting Norepinephrine Dosage After the Initial Resuscitation of Septic Shock

Authors: Dong-Kai Li, Wei Du
Affiliation: Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China

Introduction

Septic shock is a life-threatening condition. The new definitions for sepsis and septic shock (Sepsis – 3) have been published. Norepinephrine (NE) is a commonly used vasopressor in septic shock. However, after achieving the initial resuscitation goals (30 mL/kg fluid resuscitation and mean arterial pressure (MAP) > 65 mmHg), it is unclear how to adjust the NE dosage. This study aimed to explore the dosing strategy of NE based on central venous pressure (CVP) and the difference between usual MAP and current MAP (dMAP).

Background on Septic Shock

Sepsis is defined as a life-threatening organ dysfunction due to a dysregulated host response to infection. Septic shock is characterized by persistent hypotension requiring vasopressors (like NE) to maintain MAP ≥ 65 mmHg and elevated lactate levels. Optimal hemodynamic management is crucial as hypotensive patients have higher mortality. High NE dosage may cause myocardial injury, but it is also needed to correct hypotension. Tissue perfusion, indicated by lactate levels, is an important outcome measure.

Importance of MAP and CVP

MAP is the driving pressure for tissue perfusion. An adequate MAP is essential for organ perfusion in septic shock patients. CVP is a surrogate for volume status and right ventricular function. Previous studies have shown that the patient’s usual MAP is a good reference for microcirculation improvement. But how to use these parameters (CVP and MAP) to adjust NE dosage after initial resuscitation is the focus of this study.

Methods

Study Design and Setting

This was a retrospective observational study conducted in a 15 – bed mixed intensive care unit (ICU) of a tertiary care university hospital. The study included septic shock patients who had received 30 mL/kg fluid resuscitation, had MAP > 65 mmHg, and required NE.

Patient Selection

Patients admitted from June 2013 to June 2017 were eligible. Exclusion criteria included: <30 mL/kg fluid given within 3 hours after septic shock diagnosis, MAP < 65 mmHg, changes in therapy strategy (such as fluid challenges, inotrope changes, blood product transfusion, mechanical ventilation strategy changes, sedation/analgesia strategy changes) between study intervals, and incomplete data or inability to acquire usual MAP level.

Data Collection

  • Time Points: Time 1 (T1) was set before NE dosage adjustment, and Time 2 (T2) was set after adjustment (interval < 6 hours).
  • Parameters Collected: Demographic information, blood gas parameters (arterial oxygen saturation (SaO₂), arterial oxygen tension (PaO₂), arterial carbon dioxide tension (PaCO₂), standard base excess (SBE), arterial blood lactate, central venous oxygen tension (PvO₂), central venous carbon dioxide tension (PvCO₂), central venous oxygen saturation (SvO₂)), hemodynamic parameters (heart rate (HR), blood pressure, CVP), and calculation of central venous-to-arterial carbon dioxide difference (Pcv – a CO₂ = PvCO₂ – PaCO₂) and the ratio of P(v – a)CO₂/C(a – v)O₂.

Statistical Analysis

Linear regression analysis was used to determine the association between baseline characteristics (CVP, dMAP, etc.) and changes in lactate (dLac = LacT₂ – LacT₁). Mann – Whitney U test was used for comparisons when appropriate. A P < 0.05 was considered statistically significant.

Results

Baseline Characteristics

  • Patient Cohort: Out of 1560 patients initially considered, 1184 were included (600 in NE dosage increase group and 584 in NE dosage decrease group).
  • General Characteristics: The mean age was 59.3 ± 15.8 years, 63.4% were male. The most common source of infection was pneumonia (40.8%).

Factors Related to Lactate Changes

  • Linear Regression Results: In both NE dosage increase and decrease groups, CVP at T1 and dMAP at T1 were significantly related to dLac. In the NE dosage increase group, the correlation coefficient for CVP was 0.132 (P < 0.0005), and for dMAP was – 0.021. In the NE dosage decrease group, the correlation coefficient for CVP was 0.083 (P < 0.0005), and for dMAP was – 0.013 (P = 0.002).
  • Grouping Based on CVP and dMAP: Patients were divided into four groups:
    • LC HM (low CVP, high MAP): CVP 0 mmHg. Decreasing NE dosage reduced lactate levels more than increasing NE dosage (P < 0.001).
    • HC HM (high CVP, high MAP): CVP ≥ 10 mmHg, dMAP > 0 mmHg. Decreasing NE dosage also reduced lactate levels more than increasing (P = 0.001).
    • LC LM (low CVP, low MAP): CVP < 10 mmHg, dMAP ≤ 0 mmHg. Neither increasing nor decreasing NE dosage had a significant effect on dLac (P = 0.5).
    • HC LM (high CVP, low MAP): CVP ≥ 10 mmHg, dMAP ≤ 0 mmHg. Both increasing and decreasing NE dosage led to increased lactate levels, but the increase was more severe with NE dosage increase (P < 0.001).

Discussion

Interpretation of Results

  • LC HM and HC HM Groups: In these groups (where MAP was relatively high compared to usual), decreasing NE dosage was beneficial as it reduced lactate levels. This may be because in these cases, the increased NE dosage (which can cause vasoconstriction) was not necessary for maintaining perfusion, and reducing it improved tissue perfusion (as indicated by lactate clearance).
  • HC LM Group: Here, both NE dosage adjustments led to increased lactate. This could be due to the combination of high CVP (indicating possible volume overload or right ventricular dysfunction) and low MAP (compared to usual). Increasing NE dosage may further exacerbate microcirculatory dysfunction, while decreasing it may not be sufficient to maintain perfusion.
  • LC LM Group: More parameters are needed to guide NE dosage adjustment as neither increase nor decrease had a clear effect on lactate.

Comparison with Previous Studies

This study differs from previous ones as it focuses on using CVP and dMAP (a combination of volume status and perfusion pressure reference) to guide NE dosage adjustment after initial resuscitation. Previous studies often focused on specific hemodynamic targets (like CVP, ScvO₂, or MAP alone). The Surviving Sepsis Campaign guidelines do not provide clear numerical references for MAP and CVP to guide such adjustments.

Limitations

  • Single – Center Retrospective Design: Although a relatively large cohort (1184 patients) was studied, it was a single – center study. Results may not be generalizable to all settings.
  • Lactate as a Marker: While lactate is a commonly used marker for tissue perfusion in sepsis (due to microcirculatory differences), it is not a direct measure of microcirculation. Prospective studies monitoring microcirculation changes are needed to confirm the conclusions.

Conclusions

After septic shock patients (Sepsis – 3) are resuscitated to initial recovery goals, CVP and dMAP are significantly related to lactate changes (dLac). The combination of CVP and MAP (referring to usual levels) can help doctors make decisions on whether to increase or decrease NE dosage. For example, in LC HM and HC HM groups, decreasing NE dosage may be beneficial, while in HC LM group, increasing NE dosage should be cautious. This provides a practical approach for clinicians to optimize NE dosage in septic shock patients after initial resuscitation.

Future Directions

Future research should focus on prospective studies with microcirculation monitoring (such as orthogonal polarization spectral imaging or sidestream dark – field imaging) to further validate the role of CVP and MAP in NE dosage adjustment. Additionally, multi – center studies can increase the generalizability of the findings.

doi: 10.1097/CM9.0000000000000238 (available at doi.org/10.1097/CM9.0000000000000238)

Was this helpful?

0 / 0