Duc Nam Nguyen

Elevated serum levels of S-100β protein and neuron-specific enolase are associated with brain injury in patients with severe sepsis and septic shock

Objective:We investigated whether serum levels of neuron-specific enolase (NSE) and S-100&bgr; protein could be used to evaluate cerebral injury and to predict outcome in severe sepsis and severe septic shock. Design:Prospective study. Setting:University hospital. Patients and Measurements:In 170 consecutively enrolled patients with severe sepsis and septic shock, serum S-100&bgr; and NSE were measured daily during four consecutive days after intensive care unit admission. Admission Glasgow Coma Scale before sedation and daily Sequential Organ Failure Assessment scores were recorded in all patients. Acute encephalopathy was defined as either a state of agitation, confusion, irritability, and convulsions (type A) or characterized by somnolence, stupor, and coma (type B) and persistently observed during 72 hrs after withdrawing sedation. When clinically indicated, contrast computed tomography or magnetic resonance imaging were performed to evaluate brain injury. Main Results:S-100&bgr; and NSE increased in, respectively, 72 (42%) and 90 (53%) patients. High biomarker levels were associated with the maximum Sequential Organ Failure Assessment scores (p = .001), and the highest values were found in patients who died early, within 4 days of inclusion (p = .005). Low consciousness encephalopathy type B was more frequently observed in patients with elevated S-100&bgr; (p = .004). S-100&bgr; levels of ≥4 &mgr;g/L were associated with severe brain ischemia or hemorrhage, and values of <2 &mgr;g/L were found in patients with diffuse cerebral embolic infarction lesions. High S-100&bgr; levels were associated with higher intensive care unit mortality (p = .04) and represented the strongest independent predictor of intensive care unit survival, whereas NSE and the Glasgow Coma Scale failed to predict fatal outcome. Conclusions:S-100&bgr; and NSE are frequently increased and associated with brain injury in patients with severe sepsis and septic shock. S-100&bgr; levels more closely reflected severe encephalopathy and type of brain lesions than NSE and the Glasgow Coma Scale.

Effects of N-Acetyl-L-Cysteine on Regional Blood Flow during Endotoxic Shock

We previously reported that N-acetyl-L-cysteine (NAC), an oxygen free-radical scavenger, can increase the oxygen extraction capabilities during endotoxic shock when blood flow is progressively reduced. In the present study, we investigated whether the protective effects of NAC are related to an improvement in regional blood flow following endotoxemia. Fourteen anesthetized, saline-infused and ventilated dogs were divided into two groups: 7 dogs received NAC (150 mg/kg, followed by a 20 mg/kg.h infusion), and the other 7 dogs served as a control time-matching group. Thirty minutes later all the dogs received Escherichia coli endotoxin (2 mg/kg) i.v. A saline infusion was started 30 min after endotoxin challenge to restore pulmonary artery occlusion pressure to baseline and maintain it constant. Regional blood flow was measured by ultrasonic volume flowmeter. In the control group, arterial pressure, left ventricular stroke work index and systemic vascular resistance remained lower than baseline. Mesenteric, renal and femoral arterial blood flow increased but only femoral blood flow returned to baseline levels. In the NAC group, cardiac index and left ventricular stroke work index remained higher and systemic and pulmonary vascular resistance were lower than in the control group. Blood flow in mesenteric, renal and especially femoral arteries was higher than in the control group. Fractional blood flow increased only in the femoral artery. PaO2 and PvO2 had similar courses in the two groups. A higher venous admixture was associated with a higher cardiac index and a lower pulmonary vascular resistance in the NAC group. Oxygen delivery and oxygen-uptake were higher in the NAC-treated than in the control animals throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Sodium nitroprusside does not influence tissue oxygen extraction capabilities during a critical reduction in oxygen delivery

By its regulating effects on blood vessel tone, nitric oxide (NO) may play an important role in the coupling of oxygen delivery (DO2) to metabolic rate. We reasoned that if endogenous NO synthesis is an important modulator of oxygen extraction ratio (O2ER), then administration of a NO donor will alter oxygen extraction capabilities during a fall in blood flow. We studied the effects of the NO donor, nitroprusside, on the relationship between DO2 and oxygen uptake (VO2) during an acute reduction in DO2 induced by cardiac tamponade. Twenty-one healthy, anaesthetised, mechanically ventilated dogs were randomly divided into 3 groups. Group 1 (n = 7) served as control; Groups 2 and 3 were given sodium nitroprusside at 1.0 microgram/kg.min (n = 7), and 2.5 micrograms/kg.min intravenously (n = 7), respectively. All animals were given normal saline i.v. at a rate of 20 ml/kg.h throughout the study. Cardiac tamponade was induced by bolus injections of normal saline into the pericardial space. In the control animals the critical DO2 (DO2crit) was found at 10.1 +/- 1.5 ml/kg.min and critical O2ER (O2ERcrit) at 63.3 +/- 10.9%. Nitroprusside at the lower dose decreased systemic vascular resistance but did not significantly influence arterial pressure, cardiac output, DO2 or VO2; neither DO2crit nor O2ERcrit was altered (9.3 +/- 2.9 ml/kg.min and 70.4 +/- 20.9%). Nitroprusside at the higher dose induced significant decreases in mean arterial pressure and systemic vascular resistance, but had no significant effect on cardiac output. DO2crit (9.2 +/- 2.0 ml/kg.min) and O2ERcrit (59.8 +/- 13.2%) were similar to the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Cortisol is an associated-risk factor of brain dysfunction in patients with severe sepsis and septic shock

Objectives. To investigate cortisol levels in brain dysfunction in patients with severe sepsis and septic shock. Methods. In 128 septic and sedated patients, we studied brain dysfunction including delirium and coma by the evaluation of Richmond Agitation Sedation Scale (RASS), the Confusion Method Assessment in the ICU (CAM-ICU) after sedation withdrawal and the measurement of serum S100B biomarker of brain injury. Serum cortisol and S100B were measured within 12 hours after ICU admission and daily over the next four days. Results. Brain dysfunction was observed in 50% (64/128) before but in 84% (107/128) of patients after sedation withdrawal, and was more common in the patients older than 57 years (P = 0.009). Both cortisol (P = 0.007) and S100B levels (P = 0.028) were higher in patients with than patients without brain dysfunction. Cortisol levels were associated with ICU mortality (hazard ratio = 1.17, P = 0.024). Multivariate logistic regression showed that cortisol (odds ratio (OR): 2.34, 95% CI (2.01, 3.22), P = 0.02) and the combination effect of cortisol with age (OR: 1.004, 95% CI (1.002, 1.93), P = 0.038) but not S100B were associated with brain dysfunction. Conclusions. Cortisol was an associated-risk factor of brain dysfunction in patients with severe sepsis and septic shock.

High prolactin levels are associated with more delirium in septic patients

PURPOSES We investigated whether high prolactin levels were associated with delirium in septic patients because neuropsychiatric disorders are frequently associated with hyperprolactinemia. MATERIALS AND METHODS Prolactin levels were measured daily for 4 days in 101 patients with sepsis. Delirium was assessed using the Richmond Agitation Sedation Scale and the Confusion Assessment Method in the ICU. RESULTS Delirium developed in 79 patients (78%) and was more common in patients older than 65 years. Prolactin levels were higher in patients with delirium than in those without over the 4 days of observation (P = .032). In patients with delirium, higher prolactin levels were associated with a lower incidence of nosocomial infection (P = .006). Multivariable logistic regression showed that the Sequential Organ Failure Assessment score at intensive care unit admission (odds ratio, 1.24; 95% confidence interval, 1.04-1.48; P = .002) and the combined effect of prolactin levels with age (odds ratio, 1.018; 95% confidence interval, 1.01-1.031; P = .006) were associated with the development of delirium. CONCLUSIONS High prolactin levels may be a risk factor for delirium in septic patients.

Hypotension and a positive fluid balance are associated with delirium in patients with shock

The pathogenesis of delirium in critically ill patients is multifactorial. How hypotension and hypoxemia affect brain function and whether they can promote delirium remains unclear. A high cumulative positive fluid balance may also have a negative effect on brain function and promote delirium. We hypothesized that delirium would be more likely to develop in patients with low systemic arterial pressure, hypoxemia and a higher positive fluid balance, and investigated these associations in a prospective observational cohort study in patients with shock. After initial resuscitation, episodes of hypotension, defined as a mean arterial pressure (MAP) <65 mmHg or diastolic pressure <60 mmHg, and hypoxemia, defined as peripheral oxygen saturation (SpO2) <90% for more than one minute or any arterial oxygen concentration (PaO2) <90 mmHg, were recorded during the first 5 days of the ICU stay. Fluid balance was evaluated daily and the 5-day cumulative fluid balance recorded. Delirium was assessed using the Confusion Assessment Method for the ICU. A total of 252 patients were admitted with shock during the study period; 185 (73%) developed delirium. Patients who developed delirium also had more episodes of hypotension with a low MAP (p = 0.013) or diastolic pressure (p = 0.018) during the first five days of the ICU stay than those who did not. Patients with a higher cumulative fluid balance during the same period were also more likely to develop delirium (p = 0.01); there was no significant difference in the occurrence of hypoxemia between groups. Joint modeling, combining a linear-mixed model and an adjusted Cox survival model showed that low diastolic pressure (alpha effect = -0.058±0.0013, p = 0.043) and a positive cumulative fluid balance (alpha effect = 0.04±0.003, p = 0.021) were independently associated with delirium. In conclusion, low diastolic pressure and a cumulative positive fluid balance but not hypoxemia were independently associated with development of delirium in patients with shock.