Circulating presepsin (soluble CD14 subtype) as a marker of host response in patients with severe sepsis or septic shock: data from the multicenter, randomized ALBIOS trial.

PURPOSE: Presepsin is a soluble fragment of the cluster-of-differentiation marker protein 14 (CD14) involved in pathogen recognition by innate immunity. We evaluated the relation between its circulating concentration, host response, appropriateness of antibiotic therapy, and mortality in patients with severe sepsis. METHODS: Plasma presepsin was measured 1, 2, and 7 days after enrollment of 997 patients with severe sepsis or septic shock in the multicenter Albumin Italian Outcome Sepsis (ALBIOS) trial. They were randomized to albumin or crystalloids. We tested with univariate and adjusted models the association of single measurements of presepsin or changes over time with clinical events, organ dysfunctions, appropriateness of antibiotic therapy, and ICU or 90-day mortality. RESULTS: Presepsin concentration at baseline (946 [492-1,887] ng/L) increased with the SOFA score, the number of prevalent organ dysfunctions or failures, and the incidence of new failures of the respiratory, coagulation, liver, and kidney systems. The concentration decreased in ICU over 7 days in patients with negative blood cultures, and in those with positive blood cultures and appropriate antibiotic therapy; it increased with inappropriate antibiotic therapy (p = 0.0009). Baseline presepsin was independently associated with, and correctly reclassified, the risk of ICU and 90-day mortality. Increasing concentrations of presepsin from day 1 to day 2 predicted higher ICU and 90-day mortality (adjusted p < 0.0001 and 0.01, respectively). Albumin had no effect on presepsin concentration. CONCLUSIONS: Presepsin is an early predictor of host response and mortality in septic patients. Changes in concentrations over time seem to reflect the appropriateness of antibiotic therapy.

Drainage of pleural effusion in mechanically ventilated patients: time to measure chest wall compliance?

PURPOSE: Pleural effusion (PE) is commonly encountered in mechanically ventilated, critically ill patients and is generally addressed with evacuation or by fluid displacement using increased airway pressure (P(AW)). However, except when massive or infected, clear evidence is lacking to guide its management. The aim of this study was to investigate the effect of recruitment maneuvers and drainage of unilateral PE on respiratory mechanics, gas exchange, and lung volume. MATERIALS AND METHODS: Fifteen critically ill and mechanically ventilated patients with unilateral PE were enrolled. A 3-step protocol (baseline, recruitment, and effusion drainage) was applied to patients with more than 400 mL of PE, as estimated by chest ultrasound. Predefined subgroup analysis compared patients with normal vs reduced chest wall compliance (C(CW)). Esophageal and P(AW)s, respiratory system, lung and C(CW)s, arterial blood gases, and end-expiratory lung volumes were recorded. RESULTS: In the whole case mix, neither recruitment nor drainage improved gas exchange, lung volume, or tidal mechanics. When C(CW) was normal, recruitment improved lung compliance (81.9 [64.8-104.1] vs 103.7 [91.5-111.7] mL/cm H2O, P < .05), whereas drainage had no significant effect on total respiratory system mechanics or gas exchange, although it measurably increased lung volume (1717 vs 2150 mL, P < .05). In the setting of reduced C(CW), however, recruitment had no significant effect on total respiratory system mechanics or gas exchange, whereas pleural drainage improved respiratory system and C(CW)s as well as lung volume (42.7 [38.9-50.0] vs 47.0 [43.8-63.3], P < .05 and 97.4 [89.3-97.9] vs 126.7 [92.3-153.8] mL/cm H2O, P < .05 and 1580 vs 1750 mL, P < .05, respectively). CONCLUSIONS: Drainage of a moderate-sized effusion should not be routinely performed in unselected population of critically ill patients. We suggest that measurement of C(CW) may help in the decision-making process.

Severe water intoxication secondary to the concomitant intake of non-steroidal anti-inflammatory drugs and desmopressin: a case report and review of the literature.

Most of the clinical data on the safety profile of desmopressin (DDAVP), which is an effective treatment for both polyuric conditions and bleeding disorders, originate from studies on the tailoring of drug treatment, whereas few reports exist describing severe side effects secondary to drug-drug interaction. We herein describe a case of severe hyponatremia complicated by seizure and coma due to the intake of non-steroidal anti-inflammatory drugs (NSAIDs) in a patient on DDAVP replacement therapy for central diabetes insipidus (DI). A 50-yr-old Caucasian man, with congenital central DI, developed an episode of generalized tonic-clonic seizure, resulting in coma immediately after being admitted to the Emergency Unit for weakness and emesis. Based on his medical history and clinical findings, water intoxication secondary to ketoprofen intake (200 mg/day for the last 3 days) concomitant with DDAVP replacement therapy (Minirin(®) 60 mcg 4 tablets a day) was hypothesized as being the cause of the severe euvolemic hypotonic hyponatremia (natremia 113 mEq/l, plasma osmolality 238 mOsm/Kg). After standard emergency procedures, appropriate gradual restoration of serum sodium levels to the normal range was achieved in 72 hours. Hydratation was maintained according to water excretion and desmopressin therapy was re-introduced. We discuss this case report in the context of the published literature. The present report first highlights the potentially life-threatening side effects associated with over-the-counter NSAIDs during DDAVP replacement therapy for central DI. Risks and benefits of co-treatment should be carefully considered and therapeutic alternatives to NSAIDs should be recommended to patients with central DI in order to improve DDAVP safety.

Pulse and systolic pressure variation assessment in partially assisted ventilatory support.

OBJECTIVE: The use of pulse pressure variation (PPV) and systolic pressure variation (SPV) is possible during controlled ventilation (MV). Even in acute respiratory failure, controlled MV tends to be replaced by assisted ventilatory support. We tested if PPV and SPV during flow triggered synchronized intermittent mechanical ventilation (SIMV) could be as accurate as in controlled MV. METHODS: Prospective case-controlled study. Thirty patients who met criteria of weaning from controlled MV. Twenty minutes pressure support ventilation with 3 min(-1) flow triggered SIMV breathes (10 ml kg(-1)) T1, then three consecutive breaths in controlled MV (respiratory rate 12 min(-1),10 ml kg(-1)) T2. PPV and SPV were measured in T1 and T2. Correlation and Bland-Altman analysis were used to compare respective values of PPV and SPV in the two modes of ventilation. RESULTS: Significant correlations were found between dynamic indices in SIMV during pressure support ventilation and those in controlled MV mode. The mean differences between two measurements were: PPV 0.6+/-2.8% (limit of agreement: -5.0 and 6.2), SPV 0.5+/-2.3 mmHg (limit of agreement: -4.0 and 5.1). CONCLUSIONS: PPV and SPV measured during SIMV fitted with the findings in controlled MV. Dynamic indexes could be accurately monitored in patients breathing with assisted respiratory assistance adding an imposed large enough SIMV breath.

Sedation in the critically ill ventilated patient: possible role of enteral drugs.

OBJECTIVE: Sedation by the enteral route is unusual in intensive medicine. We analysed the feasibility/efficacy of long-term enteral sedation in ventilated critically ill patients. DESIGN: Prospective interventional cohort study. SETTING: General ICU. PATIENTS AND PARTICIPANTS: Forty-two patients needing ventilation and sedation for at least 4 days. INTERVENTIONS: At admission, sedation was induced with propofol or midazolam. Enteral hydroxyzine (+/- enteral lorazepam) was added in all patients within the second day. Intravenous drugs were gradually withdrawn, trying to maintain only enteral sedation after the initial 48 h. Analgesia was provided with continuous IV fentanyl. MEASUREMENTS AND RESULTS: Sedation level was assessed evaluating, on a daily basis, patients' compliance to the invasive care and comparing observed vs planned Ramsay scores three times a day. Excluding the first 2 days of patient-stabilisation and fast titration of sedation level, 577 days with ventilatory support were analysed. In 460 days (79.7%) total enteral sedation was given. This percentage rose to 94.2% when the requested Ramsay was 2 (347 days). Daily sedation was judged as adequate in 82.8% of days of total enteral sedation. Thirty-one patients had total enteral as the exclusive route of sedation. CONCLUSIONS: After 24-48 h, enteral sedation may replace, totally/in part, IV sedation in ventilated patients. Total enteral sedation easily fits the target when a Ramsay score 2 is planned. When a deeper sedation is needed, a mixed regimen is effective and lowers IV drug dosages. No side effects were reported.

Short-term noninvasive pressure support ventilation prevents ICU admittance in patients with acute cardiogenic pulmonary edema.

STUDY OBJECTIVES: Noninvasive ventilation, although effective as treatment for patients with acute cardiogenic pulmonary edema when prolonged for hours, is of limited use in the emergency department (ED). The aim of the study was to determine whether a short attempt at noninvasive pressure support ventilation avoids ICU admittance and to identify lack of response prediction variables. DESIGN: Prospective inception cohort study. SETTING: ED of a university hospital. PATIENTS: Fifty-eight consecutive patients with cardiogenic pulmonary edema who had been unresponsive to medical treatment and were admitted between January 1999 and December 2000. INTERVENTIONS: Pressure support ventilation was instituted through a full-face mask until the resolution of respiratory failure. A 15-min "weaning test" was performed to evaluate clinical stability. Responder patients were transferred to a medical ward. Nonresponding patients were intubated and were admitted to the ICU. MAIN OUTCOME MEASURES: The included optimal length of intervention, the avoidance of ICU admittance, the incidence of myocardial infarction, and predictive lack of response criteria. RESULTS: Patients completed the trial (mean [+/- SD] duration, 96 +/- 40 min). None of the responders (43 patients; 74%) was subsequently ventilated or was admitted to the ICU. Two new episodes of myocardial infarction were observed. Thirteen of 58 patients died. A mean arterial pressure of < 95 mm Hg (odds ratio [OR], 10.6; 95% confidence interval [CI], 1.8 to 60.8; p < 0.01) and COPD (OR, 9.4; 95% CI, 1.6 to 54.0; p < 0.05) at baseline predicted the lack of response to noninvasive ventilation. CONCLUSIONS: A short attempt at noninvasive ventilation is effective in preventing invasive assistance. A 15-min weaning test can identify patients who will not need further invasive ventilatory support. COPD and hypotension at baseline are negative predictive criteria.