Terry P. Clemmer

A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock.

The use of high-dose corticosteroids in the treatment of severe sepsis and septic shock remains controversial. Our study was designed as a prospective, randomized, double-blind, placebo-controlled trial of high-dose methylprednisolone sodium succinate for severe sepsis and septic shock. Diagnosis was based on the clinical suspicion of infection plus the presence of fever or hypothermia (rectal temperature greater than 38.3 degrees C [101 degrees F] or less than 35.6 degrees C [96 degrees F]), tachypnea (greater than 20 breaths per minute), tachycardia (greater than 90 beats per minute), and the presence of one of the following indications of organ dysfunction: a change in mental status, hypoxemia, elevated lactate levels, or oliguria. Three hundred eighty-two patients were enrolled. Treatment--either methylprednisolone sodium succinate (30 mg per kilogram of body weight) or placebo--was given in four infusions, starting within two hours of diagnosis. No significant differences were found in the prevention of shock, the reversal of shock, or overall mortality. In the subgroup of patients with elevated serum creatinine levels (greater than 2 mg per deciliter) at enrollment, mortality at 14 days was significantly increased among those receiving methylprednisolone (46 of 78 [59 percent] vs. 17 of 58 [29 percent] among those receiving placebo; P less than 0.01). Among patients treated with methylprednisolone, significantly more deaths were related to secondary infection. We conclude that the use of high-dose corticosteroids provides no benefit in the treatment of severe sepsis and septic shock.

A Computer-Assisted Management Program for Antibiotics and Other Antiinfective Agents

BACKGROUND AND METHODS Optimal decisions about the use of antibiotics and other antiinfective agents in critically ill patients require access to a large amount of complex information. We have developed a computerized decision-support program linked to computer-based patient records that can assist physicians in the use of antiinfective agents and improve the quality of care. This program presents epidemiologic information, along with detailed recommendations and warnings. The program recommends antiinfective regimens and courses of therapy for particular patients and provides immediate feedback. We prospectively studied the use of the computerized antiinfectives-management program for one year in a 12-bed intensive care unit. RESULTS During the intervention period, all 545 patients admitted were cared for with the aid of the antiinfectives-management program. Measures of processes and outcomes were compared with those for the 1136 patients admitted to the same unit during the two years before the intervention period. The use of the program led to significant reductions in orders for drugs to which the patients had reported allergies (35, vs. 146 during the preintervention period; P<0.01), excess drug dosages (87 vs. 405, P<0.01), and antibiotic-susceptibility mismatches (12 vs. 206, P<0.01). There were also marked reductions in the mean number of days of excessive drug dosage (2.7 vs. 5.9, P<0.002) and in adverse events caused by antiinfective agents (4 vs. 28, P<0.02). In analyses of patients who received antiinfective agents, those treated during the intervention period who always received the regimens recommended by the computer program (n=203) had significant reductions, as compared with those who did not always receive the recommended regimens (n= 195) and those in the preintervention cohort (n = 766), in the cost of antiinfective agents (adjusted mean,

Sepsis syndrome: a valid clinical entity

102 vs.

Effects of recruitment maneuvers in patients with acute lung injury and acute respiratory distress syndrome ventilated with high positive end-expiratory pressure.

427 and

Sepsis change bundles: converting guidelines into meaningful change in behavior and clinical outcome.

340, respectively; P<0.001), in total hospital costs (adjusted mean,

Randomized, placebo-controlled trial of lisofylline for early treatment of acute lung injury and acute respiratory distress syndrome

26,315 vs.

Hypothermia in the sepsis syndrome and clinical outcome

44,865 and

Effect of ibuprofen in patients with severe sepsis : a randomized, double-blind, multicenter study

35,283; P<0.001), and in the length of the hospital stay days (adjusted mean, 10.0 vs. 16.7 and 12.9; P<0.001). CONCLUSIONS; A computerized antiinfectives-management program can improve the quality of patient care and reduce costs.

Prolonged paralysis after treatment with neuromuscular junction blocking agents

The sepsis syndrome represents a systemic response to infection and is defined as hypothermia (temperature less than 96 degrees F) or hyperthermia (greater than 101 degrees F), tachycardia (greater than 90 beat/min), tachypnea (greater than 20 breath/min), clinical evidence of an infection site and with at least one end-organ demonstrating inadequate perfusion or dysfunction expressed as poor or altered cerebral function, hypoxemia (PaO2 less than 75 torr), elevated plasma lactate, or oliguria (urine output less than 30 ml/h or 0.5 ml/kg body weight.h without corrective therapy). One hundred ninety-one patients with the sepsis syndrome were evaluated prospectively and comprised the placebo group of a multicenter trial of methylprednisolone in sepsis syndrome and septic shock. Forty-five percent of the patients were found to be bacteremic. Thirty-six percent of the patients were in septic shock (sepsis syndrome plus a systolic BP less than 90 mm Hg or a decrease from baseline in systolic BP greater than 40 mm Hg) on study entry. An additional 23% of the patients developed shock after admission with 70% doing so within 24 h of study entry. Shock reversal occurred with a 73% frequency. Twenty-five percent of the patients developed the adult respiratory distress syndrome (ARDS). Mortality for the patients with sepsis syndrome who did not develop shock was 13%. Mortality for the groups of patients with shock on admission and shock postadmission was 27.5% and 43.2%, respectively. Forty-seven percent of the bacteremic patients developed shock after study admission compared to 29.6% of the nonbacteremic patients (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Multicenter Implementation of a Severe Sepsis and Septic Shock Treatment Bundle

ObjectivePositive end-expiratory pressure (PEEP) and recruitment maneuvers (RMs) may partially reverse atelectasis and reduce ventilation-associated lung injury. The purposes of this study were to assess a) magnitude and duration of RM effects on arterial oxygenation and on requirements for oxygenation support (Fio2/PEEP) in patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS) receiving ventilation with low tidal volumes and high levels of PEEP; and b) frequency of adverse respiratory and circulatory events attributable to RMs. DesignProspective, randomized, crossover study. SettingThirty-four intensive care units at 19 hospitals. PatientsSeventy-two patients with early ALI/ARDS. Baseline PEEP and Fio2 were 13.8 ± 3.0 cm H2O and 0.39 ± 0.10, respectively (mean ± sd). InterventionsWe conducted RMs by applying continuous positive airway pressure of 35–40 cm H2O for 30 secs. We conducted sham RMs on alternate days. We monitored oxyhemoglobin saturation by pulse oximetry (SpO2), Fio2/PEEP, blood pressure, and heart rate for 8 hrs after RMs and sham RMs. We examined chest radiographs for barotrauma. Measurements and Main ResultsResponses to RMs were variable. Greatest increments from baseline SpO2 within 10 mins after RMs were larger than after sham RMs (1.7 ± 0.2 vs. 0.6 ± 0.3 %, mean ± sem, p < .01). Systolic blood pressure decreased more within 10 mins after RMs (9.4 ± 1.1 vs. 3.1 ± 1.1 mm Hg, p < .01). Changes in Fio2/PEEP requirements were not significantly different at any time after RMs vs. sham RMs. Barotrauma was apparent on first radiographs after one RM and one sham RM. ConclusionsIn ALI/ARDS patients receiving mechanical ventilation with low tidal volumes and high PEEP, short-term effects of RMs as conducted in this study are variable. Beneficial effects on gas exchange in responders appear to be of brief duration. More information is needed to determine the role of recruitment maneuvers in the management of ALI/ARDS.