Non-invasive assessment of fluid responsiveness to guide fluid therapy in patients with sepsis in the emergency department: a prospective cohort study.

BACKGROUND: Little is known about optimal fluid therapy for patients with sepsis without shock who present to the ED. In this study, we aimed to quantify the effect of a fluid challenge on non-invasively measured Cardiac Index (CI) in patients presenting with sepsis without shock. METHODS: In a prospective cohort study, CI, stroke volume (SV) and systemic vascular resistance (SVR) were measured non-invasively in 30 patients presenting with sepsis without shock to the ED of a large teaching hospital in the Netherlands between May 2018 and March 2019 using the ClearSight system. After baseline measurements were performed, a passive leg raise (PLR) was done to simulate a fluid bolus. Measurements were then repeated 30, 60, 90 and 120 s after PLR. Finally, a standardised 500 mL NaCl 0.9% intravenous bolus was administered after which final measurements were done. Fluid responsiveness was defined as >15% increase in CI after a standardised fluid challenge. MEASUREMENTS AND MAIN RESULTS: Seven out of 30 (23%) patients demonstrated a >15% increase in CI after PLR and after a 500 mL fluid bolus. Fluid responders had a higher estimated glomerular filtration rate (eGFR) (64 (44-78) vs 37 (23-47), p=0.009) but otherwise similar patient and treatment characteristics as non-responders. Baseline measurements of cardiac output (CO), CI, SV and SVR were unrelated to PLR fluid responsiveness. The change in CI after PLR was strongly positive correlated to the change in CI after a 500 mL NaCl 0.9% fluid bolus (r=0.88, p<0.001). CONCLUSION: The results of the present study demonstrate that in patients with sepsis in the absence of shock, three out of four patients do not demonstrate a clinically relevant increase in CI after a standardised fluid challenge. Non-invasive CO monitoring in combination with a PLR test has the potential to identify patients who might benefit from fluid resuscitation and may contribute to a better tailored treatment of these patients.

Early hemodynamic resuscitation in septic shock: understanding and modifying oxygen delivery.

In a previous issue of Critical Care, researchers have focused on the venous-to-arterial carbon dioxide difference (Pv-aCO2) as a surrogate marker for systemic perfusion in patients with septic shock. Although the complex mechanisms responsible for an increased Pv-aCO2 in septic shock need to be further unraveled, the potential prognostic value of Pv-aCO2 seems clinically relevant and useful in daily practice in view of its easy availability.

Tissue oxygenation as a target for goal-directed therapy in high-risk surgery: a pilot study.

BACKGROUND: Tissue hypoperfusion occurs frequently during surgery and may contribute to postoperative organ dysfunction. There is a need for perioperative treatment protocols aiming at improving tissue oxygenation (StO2). We hypothesised that intra-operative optimisation of StO2 improves tissue perfusion and thus reduces postoperative complications. Furthermore, we evaluated the feasibility of the optimisation algorithm used. METHODS: We randomized 50 high-risk patients, all >65 years with ASA physical status III, who underwent major abdominal surgery under standardized balanced general anesthesia combined with epidural analgesia. Throughout surgery StO2 was monitored at the thenar eminence using near-infrared spectroscopy. All patients were treated according to a standard care algorithm. In addition, patients in the intervention group were treated with dobutamine if necessary to keep or raise StO2 ≥ 80%. Data were recorded continuously and complications were recorded during hospital stay with a maximum of 28 days. RESULTS: The number of complications was not significantly different between groups (11 vs 20; p = 0.23). Eleven patients in the intervention group had no complication, versus 7 in the control group. There was no significant difference between groups in length of stay in ICU or in hospital. Only ten patients in the intervention group received dobutamine. Administration of dobutamine resulted in a moderate 6 [-3 to 10] % increase of StO2. The overall protocol adherence was 94%. CONCLUSIONS: No statistically significant difference in outcome was realized through intraoperative optimization of StO2 values in this pilot study. The protocol used may be considered feasible for clinical practice. Further research is obligatory to define both the optimal StO2 threshold and intervention to treat tissue hypoperfusion. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01342900. Registered 21 April 2011.

Femoral venous oxygen saturation is no surrogate for central venous oxygen saturation.

OBJECTIVE: The purpose of our study was to determine if central venous oxygen saturation and femoral venous oxygen saturation can be used interchangeably during surgery and in critically ill patients. DESIGN: Prospective observational controlled study. SETTING: Nonacademic university-affiliated teaching hospital in The Netherlands. PATIENTS: One hundred cardiac outpatients, 30 high-risk surgical patients, and 30 critically ill patients. INTERVENTIONS: None. METHODS AND MAIN RESULTS: We concurrently determined femoral venous oxygen saturation and central venous oxygen saturation in a group of 100 stable cardiac patients, which served as control group. Furthermore, we determined simultaneously femoral venous oxygen saturation and central venous oxygen saturation in 30 surgical patients and in 30 critically ill patients and evaluated changes over time. Correlation and agreement of femoral venous oxygen saturation and central venous oxygen saturation were assessed, including the difference between femoral venous oxygen saturation and central venous oxygen saturation.Despite significant correlation between obtained values of femoral venous oxygen saturation and central venous oxygen saturation (rs = 0.55; p < .001), the limits of agreement were wide in the control group (mean bias 2.7% ± 7.9%; 95% limits of agreement -12.9% to 18.2%). In both the surgical and critically ill patients, limits of agreement (mean bias of -1.9% ± 9.3%; 95% limits of agreement -20.0% to 16.3%, and mean bias of 4.6% ± 14.3%; 95% limits of agreement -23.5% to 32.6%, respectively) were wide. Results for changes of femoral venous oxygen saturation and central venous oxygen saturation were similar. During initial treatment of critically ill patients, the difference between femoral venous oxygen saturation and central venous oxygen saturation including its range of variation diminished. CONCLUSION: There is lack of agreement between femoral venous oxygen saturation and central venous oxygen saturation in both stable and unstable medical conditions. Thus, femoral venous oxygen saturation should not be used as surrogate for central venous oxygen saturation.

No agreement of mixed venous and central venous saturation in sepsis, independent of sepsis origin.

INTRODUCTION: Controversy remains regarding the relationship between central venous saturation (ScvO(2)) and mixed venous saturation (SvO(2)) and their use and interchangeability in patients with sepsis or septic shock. We tested the hypothesis that ScvO(2) does not reliably predict SvO(2) in sepsis. Additionally we looked at the influence of the source (splanchnic or non-splanchnic) of sepsis on this relationship. METHODS: In this prospective observational two-center study we concurrently determined ScvO(2) and SvO(2) in a group of 53 patients with severe sepsis during the first 24 hours after admission to the intensive care units in 2 Dutch hospitals. We assessed correlation and agreement of ScvO(2) and SvO(2), including the difference, i.e. the gradient, between ScvO(2) and SvO(2) (ScvO(2) - SvO(2)). Additionally, we compared the mean differences between ScvO(2) and SvO(2) of both splanchnic and non-splanchnic group. RESULTS: A total of 265 paired blood samples were obtained. ScvO(2) overestimated SvO(2) by less than 5% with wide limits of agreement. For changes in ScvO(2) and SvO(2) results were similar. The distribution of the (ScvO(2) - SvO(2)) (< 0 or ≥ 0) was similar in survivors and nonsurvivors. The mean (ScvO(2) - SvO(2)) in the splanchnic group was similar to the mean (ScvO(2) - SvO(2)) in the non-splanchnic group (0.8 ± 3.9% vs. 2.5 ± 6.2%; P = 0.30). O(2)ER (P = 0.23) and its predictive value for outcome (P = 0.20) were similar in both groups. CONCLUSIONS: ScvO(2) does not reliably predict SvO(2) in patients with severe sepsis. The trend of ScvO(2) is not superior to the absolute value in this context. A positive difference (ScvO(2) - SvO(2)) is not associated with improved outcome.

The incidence of low venous oxygen saturation on admission to the intensive care unit: a multi-center observational study in The Netherlands.

BACKGROUND: Low mixed or central venous saturation (S(c)vO2) can reveal global tissue hypoxia and therefore can predict poor prognosis in critically ill patients. Early goal directed therapy (EGDT), aiming at an ScvO2 >/= 70%, has been shown to be a valuable strategy in patients with sepsis or septic shock and is incorporated in the Surviving Sepsis Campaign guidelines. METHODS: In this prospective observational multi-center study, we determined central venous pressure (CVP), hematocrit, pH, lactate and ScvO2 or SvO2 in a heterogeneous group of critically ill patients early after admission to the intensive care units (ICUs) in three Dutch hospitals. RESULTS: Data of 340 acutely admitted critically ill patients were collected. The mean SvO2 value was > 65% and the mean ScvO2 value was > 70%. With mean CVP of 10.3 +/- 5.5 mmHg, lactate plasma levels of 3.6 +/- 3.6 and acute physiology, age and chronic health evaluation (APACHE II) scores of 21.5 +/- 8.3, the in-hospital mortality of the total heterogeneous population was 32.0%. A subgroup of septic patients (n = 125) showed a CVP of 9.8 +/- 5.4 mmHg, mean ScvO2 values of 74.0 +/- 10.2%, where only 1% in this subgroup revealed a ScvO2 value < 50%, and lactate plasma levels of 2.7 +/- 2.2 mmol/l with APACHE II scores 20.9 +/- 7.3. Hospital mortality of this subgroup was 26%. CONCLUSION: The incidence of low ScvO2 values for acutely admitted critically ill patients is low in Dutch ICUs. This is especially true for patients with sepsis/septic shock.

Cumulative lactate and hospital mortality in ICU patients.

BACKGROUND: Both hyperlactatemia and persistence of hyperlactatemia have been associated with bad outcome. We compared lactate and lactate-derived variables in outcome prediction. METHODS: Retrospective observational study. Case records from 2,251 consecutive intensive care unit (ICU) patients admitted between 2001 and 2007 were analyzed. Baseline characteristics, all lactate measurements, and in-hospital mortality were recorded. The time integral of arterial blood lactate levels above the upper normal threshold of 2.2 mmol/L (lactate-time-integral), maximum lactate (max-lactate), and time-to-first-normalization were calculated. Survivors and nonsurvivors were compared and receiver operating characteristic (ROC) analysis were applied. RESULTS: A total of 20,755 lactate measurements were analyzed. Data are srpehown as median [interquartile range]. In nonsurvivors (n = 405) lactate-time-integral (192 [0-1881] min·mmol/L) and time-to-first normalization (44.0 [0-427] min) were higher than in hospital survivors (n = 1846; 0 [0-134] min·mmol/L and 0 [0-75] min, respectively; all p < 0.001). Normalization of lactate <6 hours after ICU admission revealed better survival compared with normalization of lactate >6 hours (mortality 16.6% vs. 24.4%; p < 0.001). AUC of ROC curves to predict in-hospital mortality was the largest for max-lactate, whereas it was not different among all other lactate derived variables (all p > 0.05). The area under the ROC curves for admission lactate and lactate-time-integral was not different (p = 0.36). CONCLUSIONS: Hyperlactatemia is associated with in-hospital mortality in a heterogeneous ICU population. In our patients, lactate peak values predicted in-hospital mortality equally well as lactate-time-integral of arterial blood lactate levels above the upper normal threshold.

Central venous-arterial pCO2 difference as a tool in resuscitation of septic patients.

PURPOSE: To investigate the interchangeability of mixed and central venous-arterial carbon dioxide differences and the relation between the central difference (pCO2 gap) and cardiac index (CI). We also investigated the value of the pCO2 gap in outcome prediction. METHODS: We performed a post hoc analysis of a well-defined population of 53 patients with severe sepsis or septic shock. Mixed and central venous pCO2 were determined earlier at a 6 h interval (T = 0 to T = 4) during the first 24 h after intensive care unit (ICU) admittance. The population was divided into two groups based on pCO2 gap (cut off value 0.8 kPa). RESULTS: The mixed pCO2 difference underestimated the central pCO2 difference by a mean bias of 0.03 ± 0.32 kPa (95 % limits of agreement: -0.62-0.58 kPa). We observed a weak relation between pCO2 gap and CI. The in hospital mortality rate was 21 % (6/29) for the low gap group and 29 % (7/24) for the high gap group; the odds ratio was 1.6 (95 % CI 0.5-5.5), p = 0.53. At T = 4 the odds ratio was 5.3 (95 % CI 0.9-30.7); p = 0.08. CONCLUSIONS: From a practical perspective, the clinical utility of central venous pCO2 values is of potential interest in determining the venous-arterial pCO2 difference. The likelihood of a bad outcome seems to be enhanced when a high pCO2 gap persists after 24 h of therapy.

Measurement of lactate in a prehospital setting is related to outcome.

OBJECTIVE: We evaluated the relationship of lactate measured in a preclinical setting with outcome. Simultaneously, we evaluated the feasibility of implementing blood lactate measurement in a prehospital setting as part of a quality improvement project. METHODS: Chart review of patients from whom serum lactate levels prospectively were obtained in a prehospital setting. Total population was divided into two groups, that is, a shock group and a non-shock group according to the predefined shock symptoms. The shock group was divided into two groups, that is, a lactate less than 4 mmol/l (subgroup I) and a lactate of at least 4 mmol/l (subgroup II). RESULTS: In about 50% of possible cases, lactate was measured in the prehospital setting. Median lactate in subgroup I (n = 74) was 3.2 (1.5-3.9) mmol/l versus 5.0 (4.0-20.0) mmol/l in subgroup II (n = 61) (P<0.0001). Significant differences were found in length of stay in intensive care unit (P = 0.03) or hospital (P = 0.04) and mortality (subgroup I 12.2% vs. subgroup II 44.3%; P = 0.002). In normotensive shock patients showing a lactate of at least 4 mmol/l (n = 27), the mortality was higher compared with normotensive shock patients with a lactate less than 4 mmol/l (n = 31) (35 vs. 7%; P<0.001). CONCLUSION: Implementation of lactate measurement in prehospital setting is feasible, and potentially clinical relevant. Lactate measured in a preclinical setting is related to outcome. Subsequent studies should evaluate whether treatment of shock patients based on prehospital lactate measurement will improve outcome.