Jasper van Bommel

Early lactate-guided therapy in intensive care unit patients: A multicenter, open-label, randomized controlled trial

RATIONALE It is unknown whether lactate monitoring aimed to decrease levels during initial treatment in critically ill patients improves outcome. OBJECTIVES To assess the effect of lactate monitoring and resuscitation directed at decreasing lactate levels in intensive care unit (ICU) patients admitted with a lactate level of greater than or equal to 3.0 mEq/L. METHODS Patients were randomly allocated to two groups. In the lactate group, treatment was guided by lactate levels with the objective to decrease lactate by 20% or more per 2 hours for the initial 8 hours of ICU stay. In the control group, the treatment team had no knowledge of lactate levels (except for the admission value) during this period. The primary outcome measure was hospital mortality. MEASUREMENTS AND MAIN RESULTS The lactate group received more fluids and vasodilators. However, there were no significant differences in lactate levels between the groups. In the intention-to-treat population (348 patients), hospital mortality in the control group was 43.5% (77/177) compared with 33.9% (58/171) in the lactate group (P = 0.067). When adjusted for predefined risk factors, hospital mortality was lower in the lactate group (hazard ratio, 0.61; 95% confidence interval, 0.43-0.87; P = 0.006). In the lactate group, Sequential Organ Failure Assessment scores were lower between 9 and 72 hours, inotropes could be stopped earlier, and patients could be weaned from mechanical ventilation and discharged from the ICU earlier. CONCLUSIONS In patients with hyperlactatemia on ICU admission, lactate-guided therapy significantly reduced hospital mortality when adjusting for predefined risk factors. As this was consistent with important secondary endpoints, this study suggests that initial lactate monitoring has clinical benefit. Clinical trial registered with www.clinicaltrials.gov (NCT00270673).

Blood lactate monitoring in critically ill patients: a systematic health technology assessment.

Objective: To decide whether the use of blood lactate monitoring in critical care practice is appropriate. We performed a systematic health technology assessment as blood lactate monitoring has been implemented widely but its clinical value in critically ill patients has never been evaluated properly. Data Source: PubMed, other databases, and citation review. Study Selection: We searched for lactate combined with critically ill patients as the target patient population. Two reviewers independently selected studies based on relevance for the following questions: Does lactate measurement: 1) perform well in a laboratory setting? 2) provide information in a number of clinical situations? 3) relate to metabolic acidosis? 4) increase workers’ confidence? 5) alter therapeutic decisions? 6) result in benefit to patients? 7) result in similar benefits in your own setting? 8) result in benefits which are worth the extra costs? Data Extraction and Synthesis: We concluded that blood lactate measurement in critically ill patients: 1) is accurate in terms of measurement technique but adequate understanding of the (an)aerobic etiology is required for its correct interpretation; 2) provides not only diagnostic but also important prognostic information; 3) should be measured directly instead of estimated from other acid‐base variables; 4) has an unknown effect on healthcare workers’ confidence; 5) can alter therapeutic decisions; 6) could potentially improve patient outcome when combined with a treatment algorithm to optimize oxygen delivery, but this has only been shown indirectly; 7) is likely to have similar benefits in critical care settings worldwide; and 8) has an unknown cost‐effectiveness. Conclusions: The use of blood lactate monitoring has a place in risk‐stratification in critically ill patients, but it is unknown whether the routine use of lactate as a resuscitation end point improves outcome. This warrants randomized controlled studies on the efficacy of lactate‐directed therapy.

The prognostic value of blood lactate levels relative to that of vital signs in the pre-hospital setting: a pilot study.

IntroductionA limitation of pre-hospital monitoring is that vital signs often do not change until a patient is in a critical stage. Blood lactate levels are suggested as a more sensitive parameter to evaluate a patients condition. The aim of this pilot study was to find presumptive evidence for a relation between pre-hospital lactate levels and in-hospital mortality, corrected for vital sign abnormalities.MethodsIn this prospective observational study (n = 124), patients who required urgent ambulance dispatching and had a systolic blood pressure below 100 mmHg, a respiratory rate less than 10 or more than 29 breaths/minute, or a Glasgow Coma Scale (GCS) below 14 were enrolled. Nurses from Emergency Medical Services measured capillary or venous lactate levels using a hand-held device on arrival at the scene (T1) and just before or on arrival at the emergency department (T2). The primary outcome measured was in-hospital mortality.ResultsThe average (standard deviation) time from T1 to T2 was 27 (10) minutes. Non-survivors (n = 32, 26%) had significantly higher lactate levels than survivors at T1 (5.3 vs 3.7 mmol/L) and at T2 (5.4 vs 3.2 mmol/L). Mortality was significantly higher in patients with lactate levels of 3.5 mmol/L or higher compared with those with lactate levels below 3.5 mmol/L (T1: 41 vs 12% and T2: 47 vs 15%). Also in the absence of hypotension, mortality was higher in those with higher lactate levels. In a multivariable Cox proportional hazard analysis including systolic blood pressure, heart rate, GCS (all at T1) and delta lactate level (from T1 to T2), only delta lactate level (hazard ratio (HR) = 0.20, 95% confidence interval (CI) = 0.05 to 0.76, p = 0.018) and GCS (HR = 0.93, 95% CI = 0.88 to 0.99, p = 0.022) were significant independent predictors of in-hospital mortality.ConclusionsIn a cohort of patients that required urgent ambulance dispatching, pre-hospital blood lactate levels were associated with in-hospital mortality and provided prognostic information superior to that provided by the patients vital signs. There is potential for early detection of occult shock and pre-hospital resuscitation guided by lactate measurement. However, external validation is required before widespread implementation of lactate measurement in the out-of-hospital setting.

The prognostic value of the subjective assessment of peripheral perfusion in critically ill patients

Objective:The physical examination of peripheral perfusion based on touching the skin or measuring capillary refill time has been related to the prognosis of patients with circulatory shock. It is unclear, however, whether monitoring peripheral perfusion after initial resuscitation still provides information on morbidity in critically ill patients. Therefore, we investigated whether subjective assessment of peripheral perfusion could help identify critically ill patients with a more severe organ or metabolic dysfunction using the Sequential Organ Failure Assessment (SOFA) score and lactate levels. Design:Prospective observational study. Setting:Multidisciplinary intensive care unit in a university hospital. Patients:Fifty consecutive adult patients admitted to the intensive care unit. Interventions:None. Measurements and Main Results:Patients were considered to have abnormal peripheral perfusion if the examined extremity had an increase in capillary refill time (>4.5 seconds) or it was cool to the examiner hands. To address reliability of subjective inspection and palpation of peripheral perfusion, we also measured forearm-to-fingertip skin-temperature gradient (Tskin-diff), central-to-toe temperature difference (Tc-toe), and peripheral flow index. The measurements were taken within 24 hours of admission to the intensive care after hemodynamic stability was obtained (mean arterial pressure >65 mm Hg). Changes in SOFA score during the first 48 hours were analyzed (&dgr;-SOFA). Individual SOFA score was significantly higher in patients with abnormal peripheral perfusion than in those with normal peripheral perfusion (9 ± 3 vs. 7 ± 2, p < 0.05). Tskin-diff, Tc-toe, and peripheral flow index were congruent with the subjective assessment of peripheral perfusion. The proportion of patients with &dgr;-SOFA score >0 was significantly higher in patients with abnormal peripheral perfusion (77% vs. 23%, p < 0.05). The logistic regression analysis showed that the odds of unfavorable evolution are 7.4 (95% confidence interval 2–19; p < 0.05) times higher for a patient with abnormal peripheral perfusion. The proportion of hyperlactatemia was significantly different between patients with abnormal and normal peripheral perfusion (67% vs. 33%, p < 0.05). The odds of hyperlactatemia by logistic regression analysis are 4.6 (95% confidence interval 1.4–15; p < 0.05) times higher for a patient with abnormal peripheral perfusion. Conclusions:Subjective assessment of peripheral perfusion with physical examination following initial hemodynamic resuscitation in the first 24 hours of admission could identify hemodynamically stable patients with a more severe organ dysfunction and higher lactate levels. Patients with abnormal peripheral perfusion had significantly higher odds of worsening organ failure than did patients with normal peripheral perfusion following initial resuscitation.

The effect of the transfusion of stored RBCs on intestinal microvascular oxygenation in the rat

BACKGROUND: Although it is known that the transfusion of stored RBCs does not always improve tissue O2 consumption under conditions of limited tissue oxygenation, the efficiency of O2 delivery to the microcirculation by stored RBCs has never been determined.

Association between blood lactate levels, Sequential Organ Failure Assessment subscores, and 28-day mortality during early and late intensive care unit stay: A retrospective observational study

Objectives:To evaluate whether the level and duration of increased blood lactate levels are associated with daily Sequential Organ Failure Assessment (SOFA) scores and organ subscores and to evaluate these associations during the early and late phases of the intensive care unit stay. Design:Retrospective observational study. Setting:Mixed intensive care unit of a university hospital. Patients:134 heterogeneous intensive care unit patients. Interventions:None. Measurements and Main Results:We calculated the area under the lactate curve above 2.0 mmol/L (lactateAUC>2). Daily SOFA scores were collected during the first 28 days of intensive care unit stay to calculate initial (day 1), maximal, total and mean scores. Daily lactateAUC>2 values were related to both daily SOFA scores and organ subscores using mixed-model analysis of variance. This was also done separately during the early (<2.75 days) and late (>2.75 days) phase of the intensive care unit stay. Compared with normolactatemic patients (n = 78), all median SOFA variables were higher in patients with hyperlactatemia (n = 56) (initial SOFA: 9 [interquartile range 4–12] vs. 4 [2–7]; maximal SOFA: 10 [5–13] vs. 5 [2–9]; total SOFA: 28 [10–70] vs. 9 [3–41]; mean SOFA: 7 [4–10] vs. 4 [2–6], all p < .001). The overall relationship between daily lactateAUC>2 and daily SOFA was an increase of 0.62 SOFA-points per 1 day·mmol/L of lactateAUC>2 (95% confidence interval, 0.41–0.81, p < .00001). During early intensive care unit stay, the relationship between lactateAUC>2 and SOFA was 1.01 (95% confidence interval, 0.53–1.50, p < .0005), and during late intensive care unit stay, this was reduced to 0.50 (95% confidence interval, 0.28–0.72, p < .0005). Respiratory (0.30, 0.22–0.38, p < .001) and coagulation (0.13, 0.09–0.18, p < .001) subscores were most strongly associated with lactateAUC>2. Conclusions:Blood lactate levels were strongly related to SOFA scores. This relationship was stronger during the early phase of intensive care unit stay, which provides additional indirect support for early resuscitation to prevent organ failure. The results confirm that hyperlactatemia can be considered as a warning signal for organ failure.

Low tissue oxygen saturation at the end of early goal-directed therapy is associated with worse outcome in critically ill patients

IntroductionThe prognostic value of continuous monitoring of tissue oxygen saturation (StO2) during early goal-directed therapy of critically ill patients has not been investigated. We conducted this prospective study to test the hypothesis that the persistence of low StO2 levels following intensive care admission is related to adverse outcome.MethodsWe followed 22 critically ill patients admitted with increased lactate levels (>3 mmol/l). Near-infrared spectroscopy (NIRS) was used to measure the thenar eminence StO2 and the rate of StO2 increase (RincStO2) after a vascular occlusion test. NIRS dynamic measurements were recorded at intensive care admission and each 2-hour interval during 8 hours of resuscitation. All repeated StO2 measurements were further compared with Sequential Organ Failure Assessment (SOFA), Acute Physiology and Chronic Health Evaluation (APACHE) II and hemodynamic physiological variables: heart rate (HR), mean arterial pressure (MAP), central venous oxygen saturation (ScvO2) and parameters of peripheral circulation (physical examination and peripheral flow index (PFI)).ResultsTwelve patients were admitted with low StO2 levels (StO2 <70%). The mean scores for SOFA and APACHE II scores were significantly higher in patients who persisted with low StO2 levels (n = 10) than in those who exhibited normal StO2 levels (n = 12) at 8 hours after the resuscitation period (P < 0.05; median (interquartile range): SOFA, 8 (7 to 11) vs. 5 (3 to 8); APACHE II, 32(24 to 33) vs. 19 (15 to 25)). There was no significant relationship between StO2 and mean global hemodynamic variables (HR, P = 0.26; MAP, P = 0.51; ScvO2, P = 0.11). However, there was a strong association between StO2 with clinical abnormalities of peripheral perfusion (P = 0.004), PFI (P = 0.005) and RincStO2 (P = 0.002). The persistence of low StO2 values was associated with a low percentage of lactate decrease (P < 0.05; median (interquartile range): 33% (12 to 43%) vs. 43% (30 to 54%)).ConclusionsWe found that patients who consistently exhibited low StO2 levels following an initial resuscitation had significantly worse organ failure than did patients with normal StO2 values, and found that StO2 changes had no relationship with global hemodynamic variables.

The relation of near-infrared spectroscopy with changes in peripheral circulation in critically ill patients

Objective:We conducted this observational study to investigate tissue oxygen saturation during a vascular occlusion test in relationship with the condition of peripheral circulation and outcome in critically ill patients. Design:Prospective observational study. Setting:Multidisciplinary intensive care unit in a university hospital. Patients:Seventy-three critically ill adult patients admitted to the intensive care unit. Interventions:None. Measurements and Main Results:Patients were followed every 24 hrs until day 3 after intensive care admission. Near-infrared spectroscopy was used to measure thenar tissue oxygen saturation, tissue oxygen saturation deoxygenation rate, and tissue oxygen saturation recovery rate after the vascular occlusion test. Measurements included heart rate, mean arterial pressure, forearm-to-fingertip skin-temperature gradient, and physical examination of peripheral perfusion with capillary refill time. Patients were stratified according to the condition of peripheral circulation (abnormal: forearm-to-fingertip skin-temperature gradient ≥4 and capillary refill time >4.5 secs). The outcome was defined based on the daily Sequential Organ Failure Assessment score and blood lactate levels. Upon intensive care unit admission, 35 (47.9%) patients had abnormal peripheral perfusion (forearm-to-fingertip skin-temperature gradient >4 or capillary refill time >4.5 secs). With the exception of the tissue oxygen saturation deoxygenation rate, tissue oxygen saturation baseline and tissue oxygen saturation recovery rate were statistically lower in patients who exhibited abnormal peripheral perfusion than in those with normal peripheral perfusion: 72 ± 9 vs. 81 ± 9; p = .001 and 1.9 ± 0.7 vs. 3.2 ± 0.9; p = .001, respectively. When a mixed-model analysis was performed over time for estimate (s) calculation, adjusted to the condition of disease, we did not find a significant clinical effect between vascular occlusion test-derived tissue oxygen saturation measurements (as response variables) and mean systemic hemodynamic variables (as independent variables): tissue oxygen saturation vs. heart rate: s (95% confidence interval) = 0.007 (–0.08; 0.09); tissue oxygen saturation vs. mean arterial pressure: s (95% confidence interval) = –0.02 (–0.12; 0.08); tissue oxygen saturation deoxygenation rate vs. heart rate: s (95% confidence interval) = 0.002 (–0.0004; 0.006); tissue oxygen saturation deoxygenation rate vs. mean arterial pressure: s (95% confidence interval) – 0.0007 (–0.003; 0.004); tissue oxygen saturation recovery rate vs. heart rate: s (95% confidence interval) = –0.009 (–0.02; –0.0015); tissue oxygen saturation recovery rate vs. mean arterial pressure: s (95% confidence interval) = 0.01 (0.002; 0.018). However, there was a strong association between tissue oxygen saturation baseline and tissue oxygen saturation recovery rate with abnormal peripheral perfusion: tissue oxygen saturation vs. abnormal peripheral perfusion: s (95% confidence interval) = –10.1 (–13.9; –6.2); tissue oxygen saturation recovery rate vs. abnormal peripheral perfusion: s (95% confidence interval) =−10.1 (−13.9; −6.2); tissue oxygen saturation recovery rate vs. abnormal peripheral perfusion: s (95% confidence interval) = −1.1 (−1.4; −0.81). Poor outcome was more closely related to abnormalities in peripheral perfusion than to tissue oxygen saturation-derived parameters. Conclusions:We found that the condition of peripheral circulation in critically ill patients strongly influences tissue oxygen saturation resting values and the tissue oxygen saturation reoxygenation rate but not the tissue oxygen saturation deoxygenation rate. In addition, changes in near-infrared spectroscopy-derived variables were independent of condition of disease and were not accompanied by any major differences in systemic hemodynamic variables.

Persistent peripheral and microcirculatory perfusion alterations after out-of-hospital cardiac arrest are associated with poor survival*

Objective: To evaluate sublingual microcirculatory and peripheral tissue perfusion parameters in relation to systemic hemodynamics during and after therapeutic hypothermia following out-of-hospital cardiac arrest. Design: Prospective observational study. Setting: Intensive cardiac care unit at a university teaching hospital. Subjects: We followed 80 patients, of whom 25 were included after out-of-hospital cardiac arrest. Intervention: In all patients, we induced therapeutic hypothermia to 33°C during the first 24 hrs of admission. Measurements and Main Results: Complete hemodynamic measurements were obtained directly on intensive cardiac care unit admission (baseline), during induced hypothermia (T1), directly after rewarming (T2), and another 24 hrs later (T3). In addition, the sublingual microcirculation was observed using sidestream dark-field imaging, and peripheral tissue perfusion was monitored with the peripheral perfusion index, capillary refill time, tissue oxygen saturation, and forearm-to-fingertip skin temperature gradient. During hypothermia, all sublingual microcirculatory parameters decreased significantly together with peripheral capillary refill time and the peripheral perfusion index, followed by a significant increase at T2. Changes in sublingual and peripheral tissue perfusion parameters were significantly related to changes in central body temperature, but not to changes in systemic hemodynamic variables such as cardiac index or mean arterial pressure. Surprisingly, these parameters were significantly lower in nonsurvivors (n = 6) at admission and after rewarming. Persistent alterations in these parameters were related with the prevalence of organ dysfunction and were highly predictive of mortality. Conclusions: Following out-of-hospital cardiac arrest, the early postresuscitation phase is characterized by abnormalities in sublingual microcirculation and peripheral tissue perfusion, which are caused by vasoconstriction due to induced systemic hypothermia and not by impaired systemic blood flow. Persistence of these alterations is associated with organ failure and death, independent of systemic hemodynamics.

Critical hematocrit in intestinal tissue oxygenation during severe normovolemic hemodilution.

BackgroundA critical point in oxygen supply for microvascular oxygenation during normovolemic hemodilution has not been identified. The relation between organ microvascular oxygen partial pressure (&mgr;Po2) and organ oxygen consumption (&OV0312;o2) during a decreasing oxygen delivery (Do2) is not well understood. The present study was designed to determine the systemic hematocrit and organ Do2 values below which organ &mgr;Po2 and &OV0312;o2 cannot be preserved by regulatory mechanisms during normovolemic hemodilution. MethodsEighteen male Wistar rats were randomized between an experimental group (n = 12), in which normovolemic hemodilution was performed with pasteurized protein solution (PPS), and a control group (n = 6). Systemic hemodynamic and intestinal oxygenation parameters were monitored. Intestinal &mgr;Po2 was measured using the oxygen-dependent quenching of palladium-porphyrin phosphorescence. ResultsBaseline values in hemodilution and control group were similar. Hemodilution decreased hematocrit to 6.2 ± 0.8% (mean ± SD). Constant central venous pressure measurements suggested maintenance of isovolemia. Despite an increasing mesenteric blood flow, intestinal Do2 decreased immediately. Initially, &mgr;Po2 was preserved, whereas mesenteric venous Po2 (Pmvo2) decreased; below a hematocrit of 15%, &mgr;Po2 decreased significantly below Pmvo2. Critical Do2 was 1.5 ± 0.5 ml·kg−1·min−1 for &OV0312;o2, and 1.6 ± 0.5 ml·kg−1·min−1 for &mgr;Po2. Critical hematocrit values for &OV0312;o2 and &mgr;Po2 were 15.8 ± 4.6% and 16.0 ± 3.5%, respectively. ConclusionsIntestinal &mgr;Po2 and &OV0312;o2 were limited by a critical decrease in Do2 and hematocrit at the same time. Beyond these critical points not only shunting of oxygen from the microcirculation could be demonstrated, but also a significant correlation between intestinal &mgr;Po2 and &OV0312;o2.