Paul A. van Beest

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

BackgroundLow 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.MethodsIn 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.ResultsData 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%.ConclusionThe 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.

Clinical review : use of venous oxygen saturations as a goal - a yet unfinished puzzle

Shock is defined as global tissue hypoxia secondary to an imbalance between systemic oxygen delivery and oxygen demand. Venous oxygen saturations represent this relationship between oxygen delivery and oxygen demand and can therefore be used as an additional parameter to detect an impaired cardiorespiratory reserve. Before appropriate use of venous oxygen saturations, however, one should be aware of the physiology. Although venous oxygen saturation has been the subject of research for many years, increasing interest arose especially in the past decade for its use as a therapeutic goal in critically ill patients and during the perioperative period. Also, there has been debate on differnces between mixed and central venous oxygen saturation and their interchangeability. Both mixed and central venous oxygen saturation are clinically useful but both variables should be used with insightful knowledge and caution. In general, low values warn the clinician about cardiocirculatory or metabolic impairment and should urge further diagnostics and appropriate action, whereas normal or high values do not rule out persistent tissue hypoxia. The use of venous oxygen saturations seems especially useful in the early phase of disease or injury. Whether venous oxygen saturations should be measured continuously remains unclear. Especially, continuous measurement of central venous oxygen saturation as part of the treatment protocol has been shown a valuable strategy in the emergency department and in cardiac surgery. In clinical practice, venous oxygen saturations should always be used in combination with vital signs and other relevant endpoints.

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

IntroductionControversy remains regarding the relationship between central venous saturation (ScvO2) and mixed venous saturation (SvO2) and their use and interchangeability in patients with sepsis or septic shock. We tested the hypothesis that ScvO2 does not reliably predict SvO2 in sepsis. Additionally we looked at the influence of the source (splanchnic or non-splanchnic) of sepsis on this relationship.MethodsIn this prospective observational two-center study we concurrently determined ScvO2 and SvO2 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 ScvO2 and SvO2, including the difference, i.e. the gradient, between ScvO2 and SvO2 (ScvO2 - SvO2). Additionally, we compared the mean differences between ScvO2 and SvO2 of both splanchnic and non-splanchnic group.ResultsA total of 265 paired blood samples were obtained. ScvO2 overestimated SvO2 by less than 5% with wide limits of agreement. For changes in ScvO2 and SvO2 results were similar. The distribution of the (ScvO2 - SvO2) (< 0 or ≥ 0) was similar in survivors and nonsurvivors. The mean (ScvO2 - SvO2) in the splanchnic group was similar to the mean (ScvO2 - SvO2) in the non-splanchnic group (0.8 ± 3.9% vs. 2.5 ± 6.2%; P = 0.30). O2ER (P = 0.23) and its predictive value for outcome (P = 0.20) were similar in both groups.ConclusionsScvO2 does not reliably predict SvO2 in patients with severe sepsis. The trend of ScvO2 is not superior to the absolute value in this context. A positive difference (ScvO2 - SvO2) is not associated with improved outcome.

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.

The incidence of low venous oxygen saturation on admission in the ICU: a multicenter observational study in the Netherlands

BackgroundLow 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.MethodsIn 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.ResultsData 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%.ConclusionThe 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.

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.

Tissue oxygen saturation as a goal, but when and where should we measure it?

Global tissue hypoxia as a result from systemic inflammatory response or circulatory failure is an important indicator of shock preceding multiple organ dysfunction syndrome (MODS). The development of MODS determines outcome of the septic patient [1]. Unrecognized and untreated global tissue hypoxia increases morbidity and mortality. Accurate detection of global tissue hypoxia is therefore of vital importance. Physical findings, conventional hemodynamic monitoring and urinary output are important factors, but usually fail at detecting global tissue hypoxia [2, 3]. A decreased central venous saturation (ScvO2) obtained from a central venous catheter can reveal a mismatch between oxygen supply and oxygen demand, hence global tissue hypoxia [1]. Decreased ScvO2 values predict poor prognosis in septic shock [4, 5]. However, low ScvO2 values are uncommon in the setting of an intensive care unit (ICU) and additional monitoring is necessary [6]. In recent years, monitoring of tissue oxygenation by nearinfrared spectroscopy has become available and has been applied in several clinical settings in order to detect global tissue hypoxia non-invasively [7]. In this issue of Journal of Clinical Monitoring and Computing Nardi et al. [8] explore the use of this technology with the aim of implementing tissue oxygen saturation (StO2) as an additional goal for hemodynamic optimisation. An association between low StO2 values and bad outcome has been described before [7] and Nardi et al. suggest that a treatment algorithm which includes StO2 may lead to treatment intensification after finishing the resuscitation bundle as suggested by international guidelines [1]. The purpose of their pilot study with 30 subjects was assessing the feasibility of StO2 monitoring in this particular setting as preparation for a larger multicentre study (NCT00167596). Several issues should be discussed here: Patients were randomized into two groups (control vs. treatment). All patients received treatment according to the Surviving Sepsis Campaign (SSC), i.e. early goal-directed therapy (EGDT) [1, 4] and the patients in the treatment arm additionally received transfusion or dobutamine to increase StO2 (target StO2 C 80 %). Such design is as clinically practical as it is unfortunate: not only did both groups receive blood transfusions and dobutamine infusions but they also received equal amounts and dosages thereof. Hence it is not surprising that they found no difference in both primary and secondary endpoints in this underpowered study. From a monitoring viewpoint it is regrettable that StO2 was not monitored and blinded in the control arm as well. As a consequence information on StO2 values is lacking and more importantly the influence of treatment on StO2 values is unknown. On top of that, in none of the patients StO2 was monitored during early resuscitation. Although this was not the primary scope of the study, persistence of low StO2 values after early treatment is prone to bad outcome [9, 10]. Consequently questions arise on how to incorporate StO2 monitoring into future sepsis resuscitation protocols. Should StO2 primarily be used as a diagnostic or also as a therapeutic monitoring tool? Exactly when should StO2 monitoring be commenced? In other words, should StO2 monitoring be placed after completion of the current EGDT protocol or should StO2 rather be the first step after presentation? This is the commentary to Olivier Nardi et al. (doi:10.1007/s10877013-9432-y).

Lactate: An unusually sensitive parameter of ensuing organ failure?

To the Editor: With interest we read the article on the association among blood lactate levels, Sequential Organ Failure Assessment subscores, and mortality by Jansen et al (1). Their retrospective results indeed suggest blood lactate levels are related to Sequential Organ Failure Assessment scores, particularly during the early phase of an intensive care unit (ICU) stay. Although the findings of Jansen et al are interesting, we would like to raise some concerns. First, the authors demonstrated differences in outcome based on area under the lactate curve (AUC) between survivors and nonsurvivors. The upper normal lactate limit was defined as 2.0 mmol/L, which was also used to compute the AUC. In survivors (n 105), the median AUC was 0 for all used lactate values (initial, maximal, total, and mean lactate). In nonsurvivors (n 29), the median AUC varied between 0 and 0.5, including the AUC of total lactate (AUC, 0.5; interquartile range, 0–2.7). We assume that the units used in this table are days/mmol/L. To understand the real lactate load, we also assumed the median length of stay in the ICU of nonsurvivors equaled the median ICU length of stay of the total population (2.75 days). This means a median total lactate load of only 2.2 mmol/L during 1 day in nonsurvivors. We think it hard to understand these values in relation to the reported differences in clinical outcome. If such a small level above the upper normal limit would mean such a strong difference in outcome, we should consider a large abasement of the normal upper limit. That is unlikely to happen. On the other hand, the AUC might prove to be an extremely sensitive parameter. Indeed, shorter duration of hyperlactemia (“lactime”) (2) and higher lactate clearance (3) are important, but if we overpraise lactate as a prognostic parameter, we would neglect the complexity of the origin of lactate both in general and in critically ill patients (4, 5). Second, Jansen et al described a clinically relevant association in the early phase of ICU stay between failure of the cardiovascular system and lactate-derived parameters. They suggested that hyperlactatemia in critically ill ICU patients illustrates the severity of the initial cardiovascular collapse. This may indicate the presence of hypoperfused organ systems without simultaneous global hypotension (6, 7). However, the Sequential Organ Failure Assessment cardiovascular subscore is not only determined by systolic blood pressure (mm Hg), but also by the use of vasopressors (in g/kg/min). The difference in use of vasopressors between survivors and nonsurvivors is not obvious from the presented data. This is unfortunate, because others have prospectively shown that patients with higher lactate clearance had favorable outcome but with inconsistent differences in either the use of vasopressors in survivors compared with nonsurvivors or patient assigned to standard therapy or early goal-directed therapy (3, 8). We agree with the authors that prospective studies are needed to improve insight in the causal relationship between hyperlactemia and individual organ dysfunction. The authors have not disclosed any potential conflicts of interest.

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.

Colloids and crystalloids: The story continues

e676 www.ccmjournal.org October 2014 • Volume 42 • Number 10 3. Udy AA, Roberts JA, Boots RJ, et al: Augmented renal clearance: Implications for antibacterial dosing in the critically ill. Clin Pharmacokinet 2010; 49:1–16 4. Carlier M, Carrette S, Roberts JA, et al: Meropenem and piperacillin/tazobactam prescribing in critically ill patients: Does augmented renal clearance affect pharmacokinetic/pharmacodynamic target attainment when extended infusions are used? Crit Care 2013; 17:R84 5. Baptista JP, Sousa E, Martins PJ, et al: Augmented renal clearance in septic patients and implications for vancomycin optimisation. Int J Antimicrob Agents 2012; 39:420–423 6. Claus BO, Hoste EA, Colpaert K, et al: Augmented renal clearance is a common finding with worse clinical outcome in critically ill patients receiving antimicrobial therapy. J Crit Care 2013; 28:695–700 7. Roberts JA, Paul SK, Akova M, et al; DALI Study: DALI: Defining antibiotic levels in intensive care unit patients: Are current β-lactam antibiotic doses sufficient for critically ill patients? Clin Infect Dis 2014; 58:1072–1083