Faculty Bibliography

OBJECTIVE: In critically ill patients, elevated blood lactate at admission is associated with poor outcome, but after aneurysmal subarachnoid hemorrhage, this has not been investigated. We studied the association between early circulating lactate and glucose with delayed cerebral ischemia and poor outcome. Lactate and glucose were both studied, hypothesizing that both may be increased due to sympathetic activation after subarachnoid hemorrhage similar to critically ill patients. DESIGN: Retrospective cohort study. SETTING: ICUs of two academic hospitals in the Netherlands. PATIENTS: Patients with aneurysmal subarachnoid hemorrhage admitted to the ICU within 24 hours after the bleed surviving beyond 48 hours after ICU admission and who had at least one lactate measurement within 24 hours after admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In 285 patients, maximal lactate and glucose levels within the first 24 hours after admission were determined. Early lactate and glucose were related with delayed cerebral ischemia-related infarction and poor outcome (a modified Rankin Scale score of 4, 5, or death at 3 mo). Delayed cerebral ischemia occurred in 84 patients (29%), and 106 patients (39%) had poor outcome. Multivariable analyses were performed with adjustment of established predictors for delayed cerebral ischemia and outcome: age, sex, World Federation of Neurological Surgeons grade at admission and Hijdra sum scores. Early lactate and glucose were strongly related (Spearman rho = 0.55; p < 0.001). Lactate and glucose were both independently associated with delayed cerebral ischemia and poor outcome in multivariable analyses with either lactate or glucose as covariates. When both lactate and glucose were included, only glucose showed an independent association with delayed cerebral ischemia (odds ratio, 1.14; 95% CI, 1.01-1.28) and only lactate showed an independent association with poor outcome (odds ratio, 1.42; 95% CI, 1.11-1.81). CONCLUSIONS: Early lactate and glucose levels after aneurysmal subarachnoid hemorrhage are associated with delayed cerebral ischemia and poor outcome, suggesting that they may be considered in conjunction with other parameters for future prognostic models.

Fluid therapy after initial resuscitation in critically ill, septic patients may lead to harmful overloading and should therefore be guided by indicators of an increase in stroke volume (SV), i.e. fluid responsiveness. Our objective was to investigate whether tissue perfusion and oxygenation are able to monitor fluid responsiveness, even after initial resuscitation. Thirty-five critically ill, septic patients underwent infusion of 250 mL of colloids, after initial fluid resuscitation. Prior to and after fluid infusion, SV, cardiac output sublingual microcirculatory perfusion (SDF: sidestream dark field imaging) and skin perfusion and oxygenation (laser Doppler flowmetry and reflectance spectroscopy) were measured. Fluid responsiveness was defined by a >/=5 or 10% increase in SV upon fluids. In responders to fluids, SDF-derived microcirculatory and skin perfusion and oxygenation increased, but only the increase in cardiac output, mean arterial and pulse pressure, microvascular flow index and relative Hb concentration and oxygen saturation were able to monitor a SV increase. Our proof of principle study demonstrates that non-invasively assessed tissue perfusion and oxygenation is not inferior to invasive hemodynamic measurements in monitoring fluid responsiveness. However skin reflectance spectroscopy may be more helpful than sublingual SDF.

PURPOSE: Microvascular perfusion may be a non-invasive indicator of fluid responsiveness. We aimed to investigate which of the microvascular perfusion parameters truly reflects fluid responsiveness independent of sympathetic reflexes. METHODS: Fifteen healthy volunteers underwent a postural change from head up tilt (HUT) to the supine position, diminishing sympathetic tone, followed by a 30 degrees passive leg raising (PLR) with unaltered tone. Prior to and after the postural changes, stroke volume (SV) and cardiac output (CO) were measured, as well as sublingual microcirculatory perfusion (sidestream dark field imaging), skin perfusion, and oxygenation (laser Doppler flowmetry and reflectance spectroscopy). RESULTS: In responders (subjects with >10 % increase in CO), the HUT to supine change increased CO, SV, and pulse pressure, while heart rate, systemic vascular resistance, and mean arterial pressure decreased. Additionally, microvascular flow index, laser Doppler flow, and microvascular hemoglobin oxygen saturation and concentration also increased. CONCLUSION: When preload and forward flow increase in association with a decrease in sympathetic activity, microvascular blood flow increases in the skin and in the sublingual area. When preload and forward flow increase with little to no change in sympathetic activity, only sublingual functional capillary density increases. Therefore, our results indicate that sublingual functional capillary density is the best parameter to use when evaluating fluid responsiveness independent of changes in sympathetic tone.

CONTEXT: Because anticipation of death is common within the intensive care unit, attention must be paid to the prevention of distressing signs and symptoms, enabling the patient to die peacefully. In the relevant studies on this subject, there has been a lack of focus on measuring determinants of comfort in this population. OBJECTIVES: To evaluate whether dying without distressing signs after the withdrawal of life-sustaining measures is possible using a newly introduced protocol and to analyze the potential influence of opioids and sedatives on time till death. METHODS: This was a prospective observational study, in two nonacademic Dutch intensive care units after the introduction of a national protocol for end-of-life care. The study lasted two years and included adult patients in whom mechanical ventilation and/or vasoactive medication was withdrawn. Exclusion criteria included all other causes of death. RESULTS: During the study period, 450 patients died; of these, 305 patients were eligible, and 241 were included. Ninety percent of patients were well sedated before and after withdrawal. Severe terminal restlessness, death rattle, or stridor was seen in less than 6%. Dosages of opioids and sedatives increased significantly after withdrawal, but did not contribute to a shorter time till death according the regression analysis. CONCLUSION: The end-of-life protocol seems effective in realizing adequate patient comfort. Most patients in whom life-sustaining measures are withdrawn are well sedated and show few signs of distress. Dosages of opioids and sedatives increase significantly during treatment withdrawal but do not contribute to time until death. Dying with a minimum of distressing signs is thus practically possible and ethically feasible.