Brainstem responses can predict death and delirium in sedated patients in intensive care unit.

OBJECTIVES: In critically ill patients, the assessment of neurologic function can be difficult because of the use of sedative agents. It is not known whether neurologic signs observed under sedation can predict short-term outcomes. The objective of this study was to assess whether abnormal brainstem responses within the first 24 hrs of sedation are associated with mortality and altered mental status postsedation. DESIGN: Observational prospective study including an initial single-center and a subsequent multicenter study to develop and then validate the prognostic models. SETTING: Three mixed and two medical intensive care units. PATIENTS: Mechanically ventilated intensive care unit patients sedated with midazolam (± sufentanyl). INTERVENTIONS: Neurologic examination including the Glasgow Coma Scale, the Assessment to Intensive Care Environment score, cranial nerve examination, response to noxious stimuli, and the cough reflex was performed. MEASUREMENTS AND MAIN RESULTS: Seventy-two patients were included in the initial group and 72 in a subsequent validation study. Neurologic responses were independent of sedative dose. Twenty-two patients in the development cohort and 21 (29%) in the validation group died within 28 days of inclusion. Adjusted for Simplified Acute Physiology Score II score, absent cough reflex was independently associated with 28-day mortality in the development (adjusted odds ratio [OR], 7.80; 95% confidence interval [CI], 2.00-30.4; p = .003) and validation groups (adjusted OR, 5.44; 95% CI, 1.35-22.0; p = .017). Absent oculocephalic response, adjusted for Simplified Acute Physiology Score II score, was independently associated with altered mental status after the withdrawal of sedation in the development (adjusted OR, 4.54; 95% CI, 1.34-15.4; p = .015) and validation groups (adjusted OR, 6.10; 95% CI, 1.18-25.5; p = .012). CONCLUSIONS: Assessment of brainstem responses is feasible in sedated critically ill patients and loss of selected responses is predictive of mortality and altered mental status.

Osmoregulation of vasopressin secretion is altered in the postacute phase of septic shock.

OBJECTIVE: To determine whether septic shock patients have an abnormal reponse to increasing osmolarity. DESIGN: Prospective interventional study. SETTING: Intensive care unit at Raymond Poincaré and Etampes Hospitals. PATIENTS: Normonatremic patients at > 72 hrs from septic shock onset. INTERVENTION: Osmotic challenge consisting of infusing 500 mL of hypertonic saline solution (with cumulative amount of sodium not exceeding 24 g) over 120 mins. MEASUREMENTS AND MAIN RESULTS: Plasma arginine vasopressin levels were measured 15 mins before the test and then four times every 30 mins. A slope of the relation between arginine vasopressin and plasma sodium levels of < 0.5 pg/mEq defined nonresponders. Among the 33 included patients, 17 (52%) were nonresponders. During osmotic challenge, variations throughout the test in plasma sodium levels, blood pressure, and central venous pressure were comparable between the two groups. Arginine vasopressin increased from 4.8 pg/mL [3.3-6.4 pg/mL] to 14.4 pg/mL [11.2-23.3 pg/mL] in responders but only from 2.8 pg/mL [2.3-4.0 pg/mL] to 4.0 pg/mL [3.1-5.3 pg/mL] in nonresponders (p < .0001). Responders had a higher plasma arginine vasopressin levels at baseline and a more severe hematosis alteration. Nonresponders had more frequently bacteremia and liver dysfunction, been referred from the ward and undergone surgery. Critical illness severity, hemodynamic alteration, hydroelectrolytic disturbances, treatment, and outcome did not differ between the two groups. CONCLUSION: Osmoregulation is dramatically altered in half of patients with prolonged septic shock.

Sepsis-associated encephalopathy and its differential diagnosis.

Sepsis is often complicated by an acute and reversible deterioration of mental status, which is associated with increased mortality and is consistent with delirium but can also be revealed by a focal neurologic sign. Sepsis-associated encephalopathy is accompanied by abnormalities of electroencephalogram and somatosensory-evoked potentials, increased in biomarkers of brain injury (i.e., neuron-specific enolase, S-100 beta-protein) and, frequently, by neuroradiological abnormalities, notably leukoencephalopathy. Its mechanism is highly complex, resulting from both inflammatory and noninflammatory processes that affect all brain cells and induce blood-brain barrier breakdown, dysfunction of intracellular metabolism, brain cell death, and brain injuries. Its diagnosis relies essentially on neurologic examination that can lead one to perform specific neurologic tests. Electroencephalography is required in the presence of seizure; neuroimaging in the presence of seizure, focal neurologic signs or suspicion of cerebral infection; and both when encephalopathy remains unexplained. In practice, cerebrospinal fluid analysis should be performed if there is any doubt of meningitis. Hepatic, uremic, or respiratory encephalopathy, metabolic disturbances, drug overdose, withdrawal of sedatives or opioids, alcohol withdrawal delirium, and Wernicke's encephalopathy are the main differential diagnoses of sepsis-associated encephalopathy. Patient management is based mainly on controlling infection, organ system failure, and metabolic homeostasis, at the same time avoiding neurotoxic drugs.