Faculty Bibliography

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.

PURPOSE: To study and compare the relationship between end-expiratory lung volume (EELV) and changes in end-expiratory lung impedance (EELI) measured with electrical impedance tomography (EIT) at the basal part of the lung at different PEEP levels in a mixed ICU population. METHODS: End-expiratory lung volume, EELI and tidal impedance variation were determined at four PEEP levels (15-10-5-0 cm H2O) in 25 ventilated ICU patients. The tidal impedance variation and tidal volume at 5 cm H2O PEEP were used to calculate change in impedance per ml; this ratio was then used to calculate change in lung volume from change in EELI. To evaluate repeatability, EELV was measured in quadruplicate in five additional patients. RESULTS: There was a significant but relatively low correlation (r = 0.79; R2 = 0.62) and moderate agreement (bias 194 ml, SD 323 ml) between DeltaEELV and change in lung volume calculated from the DeltaEELI. The ratio of tidal impedance variation and tidal volume differed between patients and also varied at different PEEP levels. Good agreement was found between repeated EELV measurements and washin/washout of a simulated nitrogen washout technique. CONCLUSION: During a PEEP trial, the assumption of a linear relationship between change in global tidal impedance and tidal volume cannot be used to calculate EELV when impedance is measured at only one thoracic level just above the diaphragm.

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 (delta-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 delta-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.

BACKGROUND: Hyperlactatemia and its reduction after admission in the intensive care unit (ICU) have been related to survival. Because it is unknown whether this equally applies to different groups of critically ill patients, we compared the prognostic value of repeated lactate levels (a) in septic patients versus patients with hemorrhage or other conditions generally associated with low-oxygen transport (LT) (b) in hemodynamically stable versus unstable patients. METHODS: In this prospective observational two-center study (n = 394 patients), blood lactate levels at admission to the ICU (Lac(T0)) and the reduction of lactate levels from T = 0 to T = 12 hours (DeltaLac(T0-12)) and from T = 12 to T = 24 hours (DeltaLac(T12-24)), were related to in-hospital mortality. RESULTS: Reduction of lactate was associated with a lower mortality only in the sepsis group (DeltaLac(T0-12): hazard ratio [HR] 0.34, p = 0.004 and DeltaLac(T12-24): HR 0.24, p = 0.003), but not in the LT group (DeltaLac(T0-12); HR 0.78, p = 0.52 and DeltaLac(T12-24); HR 1.30, p = 0.61). The prognostic values of Lac(T0), DeltaLac(T0-12), and DeltaLac(T12-24) were similar in hemodynamically stable and unstable patients (p = 0.43). CONCLUSIONS: Regardless of the hemodynamic status, lactate reduction during the first 24 hours of ICU stay is associated with improved outcome only in septic patients, but not in patients with hemorrhage or other conditions generally associated with LT. We hypothesize that in this particular group a reduction in lactate is not associated with improved outcome due to irreversible damage at ICU admission.

OBJECTIVE: Compare duration of mechanical ventilation (MV), weaning time, ICU-LOS (ICU-LOS), efficacy and safety of remifentanil-based regimen with conventional sedation and analgesia. DESIGN: Centre randomised, open-label, crossover, 'real-life' study. SETTING: 15 Dutch hospitals. PATIENTS: Adult medical and post-surgical ICU patients with anticipated short-term (2-3 days) MV. INTERVENTIONS: Patient cohorts were randomised to remifentanil-based regimen (n = 96) with propofol as required, for a maximum of 10 days, or to conventional regimens (n = 109) of propofol, midazolam or lorazepam combined with fentanyl or morphine. MEASUREMENTS AND MAIN RESULTS: Outcomes were weaning time, duration of MV, ICU-LOS, sedation- and analgesia levels, intensivist/ICU nurse satisfaction, adverse events, mean arterial pressure, heart rate. Median duration of ventilation (MV) was 5.1 days with conventional treatment versus 3.9 days with remifentanil (NS). The remifentanil-based regimen reduced median weaning time by 18.9 h (P = 0.0001). Median ICU-LOS was 7.9 days versus 5.9 days, respectively (NS). However, the treatment effects on duration of MV and ICU stay were time-dependent: patients were almost twice as likely to be extubated (P = 0.018) and discharged from the ICU (P = 0.05) on day 1-3. Propofol doses were reduced by 20% (P = 0.05). Remifentanil also improved sedation-agitation scores (P < 0.0001) and intensivist/ICU nurse satisfaction (P < 0.0001). All other outcomes were comparable. CONCLUSIONS: In patients with an expected short-term duration of MV, remifentanil significantly improves sedation and agitation levels and reduces weaning time. This contributes to a shorter duration of MV and ICU-LOS.

Important ethical aspects apply to the process of obtaining consent in emergency critical care research: the incapacity of almost all patients for giving informed consent and the emergency and life-threatening nature of the conditions involved, resulting in short therapeutic time frames. We argue that deferred proxy consent is the preferable substitute for informed patient consent in emergency critical care research. However, researchers can face two problems when using this consent procedure. First, can proxies give a valid judgment for consent or refusal in the acute phase of the life-threatening illness of their relative, and second, what should researchers do with already obtained data when study procedures are finished (e.g., because the patient has died) before proxies can be informed and consent be sought? We propose approaching the relatives with information about the trial and asking them for consent only if it is ethically valid to do so. The first psychological distress may prohibit a complete understanding of the information, which is necessary for a true and valid informed proxy consent. In addition, we recommend using the study data if study procedures are finished before proxies can be informed and consent be sought, provided sufficient privacy measures have been applied.

INTRODUCTION: To assess potential metabolic and microcirculatory alterations in critically ill patients, near-infrared spectroscopy (NIRS) has been used, in combination with a vascular occlusion test (VOT), for the non-invasive measurement of tissue oxygen saturation (StO2), oxygen consumption, and microvascular reperfusion and reactivity. The methodologies for assessing StO2 during a VOT, however, are very inconsistent in the literature and, consequently, results vary from study to study, making data comparison difficult and potentially inadequate. Two major aspects concerning the inconsistent methodology are measurement site and probe spacing. To address these issues, we investigated the effects of probe spacing and measurement site using 15 mm and 25 mm probe spacings on the thenar and the forearm in healthy volunteers and quantified baseline, ischemic, reperfusion, and hyperemic VOT-derived StO2 variables. METHODS: StO2 was non-invasively measured in the forearm and thenar in eight healthy volunteers during 3-minute VOTs using two InSpectra tissue spectrometers equipped with a 15 mm probe or a 25 mm probe. VOT-derived StO2 traces were analyzed for base-line, ischemic, reperfusion, and hyperemic parameters. Data were categorized into four groups: 15 mm probe on the forearm (F15 mm), 25 mm probe on the forearm (F25 mm), 15 mm probe on the thenar (T15 mm), and 25 mm probe on the thenar (T25 mm). RESULTS: Although not apparent at baseline, probe spacing and measurement site significantly influenced VOT-derived StO2 variables. For F15 mm, F25 mm, T15 mm, and T25 mm, StO2 ownslope was -6.4 +/- 1.7%/minute, -10.0 +/- 3.2%/minute, -12.5 +/- 3.0%/minute, and -36.7 +/- 4.6%/minute, respectively. StO2 upslope was 105 +/- 34%/minute, 158 +/- 55%/minute, 226 +/- 41%/minute, and 713 +/- 101%/minute, and the area under the hyperemic curve was 7.4 +/- 3.8%.minute, 10.1 +/- 4.9%.minute, 12.6 +/- 4.4%.minute, and 21.2 +/- 2.7%.minute in these groups, respectively. Furthermore, the StO2 parameters of the hyperemic phase of the VOT, such as the area under the curve, significantly correlated to the minimum StO2 during ischemia. CONCLUSIONS: NIRS measurements in combination with a VOT are measurement site-dependent and probe-dependent. Whether this dependence is anatomy-, physiology-, or perhaps technology-related remains to be elucidated. Our study also indicated that reactive hyperemia depends on the extent of ischemic insult.

INTRODUCTION: The 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. METHODS: We 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)). RESULTS: Twelve 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%)). CONCLUSIONS: We 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.

During recent years increasing attention has been given to the quality of survival in critical care. Health-related quality of life (HRQOL) is an important issue both for patients and their families. Furthermore, admission to the intensive care unit can have adverse psychological effects in critically ill patients. Recent studies conducted in critically ill patients have measured HRQOL. However, usually absent from such reports are evaluations of conceptual issues, addressing factors such as why HRQOL should be measured in critically ill patients, how to define and standardize domains of HRQOL, whether proxies can provide useful information about HRQOL in critically ill patients, whether response shift occurs in critically ill patients, and whether post-traumatic stress disorder (PTSD) occurs in critically ill patients. Some studies reported moderate agreement between patients and their proxies, although lower levels of agreement may be reported for psychosocial or physical functioning. Response shift (adaptation and change in perception) appears to be an important phenomenon and likely to be present, but it is seldom measured when estimating HRQOL in critically ill patients. Furthermore, vigilance for symptoms of PTSD and early interventions to prevent PTSD are needed.

BACKGROUND: Severe sepsis is frequently complicated by organ failure and accompanied by high mortality. Patients surviving severe sepsis can have impaired health-related quality of life (HRQOL). The time course of changes in HRQOL in severe sepsis survivors after discharge from the intensive care unit (ICU) and during a general ward stay have not been studied. METHODS: We performed a long-term prospective study in a medical-surgical ICU. Patients with severe sepsis (n = 170) admitted for >48 h were included in the study. We used the Short-form 36 to evaluate the HRQOL of severe sepsis patients before ICU and hospital stay and at 3 and 6 mo after ICU discharge. Furthermore, we compared the results for ICU admission and 6 mo after ICU discharge with those of an age-matched general Dutch population. RESULTS: At 6 mo after ICU discharge, 95 patients could be evaluated (eight patients were lost to follow-up, 67 died). HRQOL showed a multidimensional decline during the ICU stay and gradual improvement over the 6 mo after ICU discharge for the social functioning, vitality, role-emotional, and mental health dimensions. However, 6 mo after ICU discharge, scores for the physical functioning, role-physical, and general health dimensions were still significantly lower than preadmission values. Physical and Mental Component Scores changed significantly over time. In particular, the Mental Component Score showed a small decline at ICU discharge but recovered rapidly, and at 6 mo after ICU discharge had improved to near normal values. In addition, Short-form 36 scores were lower than those in a matched general population in six of the eight dimensions, with the exception of social functioning and bodily pain. Interestingly, the preadmission HRQOL in surviving patients was already lower in three of the eight dimensions (role-physical, mental health, and vitality) when compared with the general population. CONCLUSIONS: Severe sepsis patients demonstrate a sharp decline of HRQOL during ICU stay and a gradual improvement during the 6 mo after ICU discharge. Recovery begins after ICU discharge to the general ward. Nevertheless, recovery is incomplete in the physical functioning, role-physical, and general health dimensions at 6 mo after ICU discharge compared with preadmission status.