Gourang P. Patel

Systemic Steroids in Severe Sepsis and Septic Shock

Despite more than 5 decades of study and debate, the role of corticosteroid treatment in patients with severe sepsis and septic shock remains controversial. Data support a beneficial effect on systemic blood pressure in patients with septic shock. However, the ability of corticosteroid therapy to improve mortality in patients with severe sepsis and septic shock remains controversial, with contradictory results from recent large multicenter clinical trials. Although it appears clear that high-dose corticosteroid treatment provides no benefit and possibly harm in septic patients, the experimental design flaws and biases of recent low-dose (physiologic) steroid treatment trials limit their ability to provide adequate answers to the important questions of which septic patients should be treated, how much steroid to give, and the optimum duration of treatment. Unfortunately, the answer to these important questions is not readily evident based on the current evidence or the application of metaanalysis to the available clinical data. This concise evidence-based review highlights the strengths and weaknesses of the current data to inform the practicing clinician as to which patients are likely to derive significant benefit from corticosteroid treatment, while we await more definitive guidance from future multicenter, prospective, randomized, controlled trials designed to better answer these important therapeutic questions.

Efficacy and safety of dopamine versus norepinephrine in the management of septic shock.

The optimum septic shock vasopressor support strategy is currently debated. This study was performed to evaluate the efficacy and safety of norepinephrine (NE) and dopamine (DA) as the initial vasopressor in septic shock patients who were managed with a specific treatment protocol. A prospective, randomized, open-label, clinical trial was used in a medical intensive care unit comparing DA with NE as the initial vasopressor in fluid-resuscitated 252 adult patients with septic shock. If the maximum dose of the initial vasopressor was unable to maintain the hemodynamic goal, then fixed-dose vasopressin was added to each regimen. If additional vasopressor support was needed to achieve the hemodynamic goal, then phenylephrine was added. The primary efficacy end point was all-cause 28-day mortality. Secondary end points included organ dysfunction, hospital and intensive care unit length of stay, and safety (primarily occurrence of arrhythmias). The 28-day mortality rate was 50% (67/134) with DA as the initial vasopressor compared with 43% (51/118) for NE treatment (P = 0.282). There was a significantly greater incidence of sinus tachycardia with DA (24.6%; 33/134) than NE (5.9%; 7/118) and arrhythmias noted with DA treatment (19.4%; 26/134) compared with NE treatment (3.4%; 4/118; P < 0.0001), respectively. Logistic regression analysis identified Acute Physiologic and Chronic Health Evaluation II score (P < 0.0001) and arrhythmia (P < 0.015) as significant predictors of outcome. In this protocol-directed vasopressor support strategy for septic shock, DA and NE were equally effective as initial agents as judged by 28-day mortality rates. However, there were significantly more cardiac arrhythmias with DA treatment. Patients receiving DA should be monitored for the development of cardiac arrhythmias (NCT00604019).

Reducing Use of Indwelling Urinary Catheters and Associated Urinary Tract Infections

BACKGROUND Use of indwelling urinary catheters can lead to complications, most commonly catheter-associated urinary tract infections. Duration of catheterization is the major risk factor. These infections can result in sepsis, prolonged hospitalization, additional hospital costs, and mortality. OBJECTIVES To implement and evaluate the efficacy of an intervention to reduce catheter-associated urinary tract infections in a medical intensive care unit by decreasing use of urinary catheters. METHODS Indications for continuing urinary catheterization with indwelling devices were developed by unit clinicians. For a 6-month intervention period, patients in a medical intensive care unit who had indwelling urinary catheters were evaluated daily by using criteria for appropriate catheter continuance. Recommendations were made to discontinue indwelling urinary catheters in patients who did not meet the criteria. Days of use of a urinary catheter and rates of catheter-associated urinary tract infections during the intervention were compared with those of the preceding 11 months. RESULTS During the study period, 337 patients had a total of 1432 days of urinary catheterization. With use of guidelines, duration of use was significantly reduced to a mean of 238.6 d/mo from the previous rate of 311.7 d/mo. The number of catheter-associated urinary tract infections per 1000 days of use was a mean of 4.7/mo before the intervention and zero during the 6-month intervention period. CONCLUSIONS Implementation of an intervention to judge appropriateness of indwelling urinary catheters may result in significant reductions in duration of catheterization and occurrences of catheter-associated urinary tract infections.

The effect of time to antifungal therapy on mortality in Candidemia associated septic shock.

The timely administration of appropriate antifungal therapy for Candida bloodstream infections (CBSI) improves clinical outcomes. However, little data exist on the effect of antifungal therapy in patients with septic shock and candidemia. We describe antifungal treatment of patients with septic shock due to CBSI and its impact on in-hospital mortality. We retrospectively reviewed medical records of hospitalized patients identified with at least one positive blood culture for Candida between January 2003 and June 2007. All septic shock patients received vasopressor therapy and had candidemia within 72 hours of refractory shock. Data collected included demographics, comorbidities, antibiotic exposure, in-hospital mortality, and intensive care-related factors. Acute Physiology and Chronic Health Evaluation II scores were calculated. Time to antifungal therapy was defined as the interval between time of collection of the first positive Candida blood culture and the time when appropriate antifungal therapy was initiated. Univariate and multivariate analyses were performed to identify variables associated with in-patient mortality. Classification and regression tree analysis was used to identify the mortality breakpoint between early and late antifungal therapy. Septic shock developed in 23% (31 of 135) patients with CBSI. In-hospital mortality was 68%. Nonalbicans Candida spp. accounted for 48% of blood isolates. Appropriate antifungal therapy was administered to 24 patients; 15 (63%) of these patients died. Classification and regression tree analysis revealed that patients who received appropriate antifungal therapy within 15 hours of collecting the first positive Candida blood culture had improved survival (P = 0.03). Early, appropriate antifungal therapy improves survival among patients with septic shock due to CBSI.

Comparison of outcomes from daptomycin or linezolid treatment for vancomycin-resistant enterococcal bloodstream infection: A retrospective, multicenter, cohort study.

BACKGROUND The optimal treatment for bloodstream infections (BSIs) with vancomycin-resistant enterococci (VRE) is unknown. OBJECTIVE This study examined outcomes in patients treated with daptomycin or linezolid for VRE BSI. METHODS A retrospective, multicenter, cohort study was performed via chart review. Hospitalized patients treated for VRE BSI with daptomycin or linezolid from September 1, 2003, to June 30, 2007, were identified via pharmacy and microbiology reports at each institution. Patients aged <18 years or with polymicrobial bacteremia were excluded from analysis. Linezolid and daptomycin were included because the participating institutions used either of the 2 agents as first-line treatment for VRE BSI. Univariate and multivariate analyses were performed to determine the effect of drug selection on mortality and duration of BSI. Duration of BSI was defined as the amount of time from the draw date of the first positive blood culture to the draw date of the first finalized negative blood culture. Adverse events were not assessed. RESULTS One-hundred one patients from 3 participating US hospitals experiencing VRE BSI were identified. Sixty-seven patients were treated with daptomycin and 34 with linezolid. Baseline characteristics appeared comparable between the daptomycin- and linezolidtreated groups, with the exception of shock (P = 0.049), prior vancomycin treatment (P = 0.002), and prior linezolid treatment (P < 0.001), all of which occurred significantly more often in daptomycin-treated patients. Inpatient mortality occurred in 31 daptomycin- and 10 linezolid-treated patients (46.3% vs 29.4%; P = NS). Linear regression found that shock (P = 0.015), infective endocarditis (P = 0.021), and concurrent rifampin or gentamicin treatment (P = 0.01) were associated with prolonged duration of positive cultures. Logistic regression revealed that shock (odds ratio [OR] = 14.24; P = 0.008), infection with Enterococcus faecium (OR = 53.10; P = 0.024), previous linezolid treatment (OR = 6.63; P = 0.031), concurrent rifampin or gentamicin treatment (OR = 6.48; P = 0.046), and a nonline source of infection (OR = 6.67; P = 0.019) were associated with increased mortality. CONCLUSIONS In this retrospective cohort analysis, there were no significant differences in mortality of VRE BSI between patients receiving daptomycin or linezolid. Underlying comorbidities appeared to best predict outcome; however, given the retrospective nature of this study, larger, prospective, randomized, comparative studies are needed to control for potential biases and determine definitive outcome differences between these 2 antimicrobials.

New treatment strategies for severe sepsis and septic shock.

Purpose of reviewSevere sepsis and septic shock are common causes of morbidity and mortality in critically ill patients. The complexities of the septic cascade continue to emerge and may identify new targets for innovative patient management. This review will highlight some of the recent advances in our management of the patient with sepsis. Recent findingsThe early administration of adequate antibiotic therapy, effective source control, and goal-directed hemodynamic resuscitation are the cornerstone of successful management. Prevention of the complications of critical illness and maintenance of normal glucose levels are also important elements of effective management. In patients with vasopressor-dependent septic shock, evaluation for inadequate cortisol response and the provision of physiologic doses of replacement steroids for those found to be deficient may result in improved survival. Administration of drotrecogin alfa (activated), (activated protein C) has been shown to improve survival in patients with severe sepsis and septic shock who have a high risk of mortality. Because of its anticoagulant properties, caution must be exercised with the use of activated protein C in those patients who meet the contraindications for its use or who have risk factors for increased bleeding complications. SummarySignificant advances have been made in our understanding of the septic cascade and our ability to manage patients with severe sepsis and septic shock. Despite these advances, significant morbidity and mortality continue. In addition, there is also considerable impact on the financial and overall function of the patient.

Impact of the Implementation of a Sepsis Protocol for the Management of Fluid-Refractory Septic Shock: A Single-Center, Before-and-After Study

BACKGROUND Evidence-based guidelines have been published for the acute management of severe sepsis and septic shock. Key goals of institution-driven protocols include timely fluid resuscitation and antibiotic selection, as well as source control. OBJECTIVE This study assessed the impact of a sepsis protocol on the timeliness of antibiotic administration, the adequacy of fluid resuscitation, and 28-day mortality in patients with fluid-refractory septic shock. METHODS This was a single-center, before-and-after study (18 months before July 2007 and 18 months after) with prospective data collection evaluating the outcomes of a sepsis protocol in adult patients with fluid-refractory septic shock. All patients received a fluid challenge and antibiotics; those who did not were excluded from this analysis. Preprotocol findings led to the development of the sepsis protocol, which emphasized fluid resuscitation, timely administration of antibiotic therapy, and collection of specimens for culture at the onset of septic shock. In the pre- and postprotocol phases of the study, data were collected prospectively and analyzed for demographic characteristics; Acute Physiology and Chronic Health Evaluation (APACHE) II score; appropriateness of fluid resuscitation; antibiotic use; number of vasopressor, ventilator, and intensive care unit (ICU) days; and 28-day mortality. Outcomes were measured prospectively at any time during the patients hospital admission. The primary end points were the time to administration of antimicrobial therapy and the appropriateness of fluid resuscitation before and after implementation of the sepsis protocol. RESULTS A total of 118 patients were included in the analysis: 64 and 54 in the pre- and postprotocol groups, respectively. Patients in the preprotocol group were primarily women (53% [34/64]) and had a mean (SD) age of 61 (15.5) years and a mean APACHE II score of 28 (6.0). Patients in the postprotocol group were primarily men (54% [29/54]) and had a mean age of 52 (18.0) years and a mean APACHE II score of 27 (6.4). Implementation of the sepsis protocol resulted in a greater percentage of patients receiving timely antibiotic therapy (ie, within 4.5 hours of refractory shock; 85% [46/54] vs 56% [36/64]; P = 0.001) and adequate fluid resuscitation (72% [39/54] vs 31% [20/64]; P < 0.001) compared with the preprotocol group. Post hoc analysis found significant decreases in the number of vasopressor days (mean [SD], 3.8 [2.7] to 1.4 [1.5]; P < 0.001), ventilator days (9.1 [12.2] to 2.7 [4.0]; P < 0.001), and ICU days (12.3 [12.6] to 4.9 [3.9]; P < 0.001) in the postprotocol group. In-hospital mortality was not significantly different between the groups (survival 46% [28/61] before vs 54% [33/61] after the protocol). Multivariate analysis for predictors of in-hospital mortality identified an interval between shock and empiric antibiotic administration of >4.5 hours (odds ratio [OR] = 5.54; 95% CI, 1.91-16.07; P < 0.002), vasopressor duration in days (OR = 1.27; 95% CI, 1.01-1.59; P = 0.037), APACHE II score (OR = 1.14; 95% CI, 1.05-1.24; P = 0.003), and type of infection (community vs nosocomial, OR = 0.18; 95% CI, 0.05-0.61; P = 0.006) as significant predictors. The 28-day mortality decreased from 61% (39/64) to 33% (18/54) after implementation of the protocol (P = 0.004). CONCLUSION Implementation of a sepsis protocol emphasizing early administration of antibiotic therapy and adequate fluid resuscitation was associated with improved clinical outcomes and lower 28-day mortality in patients with fluid-refractory septic shock at this institution.

The application of intermittent pneumatic compression devices for thromboprophylaxis: AN observational study found frequent errors in the application of these mechanical devices in ICUs.

Objective Because venous thromboembolism (VTE) can be a devastating consequence of critical illness, patients should receive thromboprophylaxis using chemical or mechanical strategies or both. Mechanical strategies such as intermittent pneumatic compression (IPC) devices are in widespread use; this study sought to assess clinicians’ adherence to ordered IPC devices in critically ill patients. Methods A month-long prospective, observational study was conducted in a convenience sample of 108 mechanically ventilated patients in four adult ICUs in an urban academic medical center. Observations of prescribed IPC device applications were made twice daily by nurses using a standardized checklist. Results Nine hundred sixty-six observations were made of 108 patients, 47 (44%) of whom were ordered to receive thromboprophylaxis with IPC devices alone and 61 (56%) to receive IPC devices in combination with an anticoagulant. Errors in IPC device application were found in 477 (49%) of the observations. Patients received no IPC prophylaxis in 142 (15%) of total observations. In 45 of 342 (13%) of the observations, IPC devices were the only type of thromboprophylaxis ordered. Half of the misapplications related to improper placement of sleeves to legs. Misapplications did not differ in type or frequency between shifts. Implications The researchers observed frequent misapplications of ordered IPC devices. Future study is necessary to illuminate the consequences of such errors.

Assessing the influence of registered dietitian order-writing privileges on parenteral nutrition use.

Previous studies have examined the influence of a nutrition support team on parenteral nutrition (PN) use; however, the influence of registered dietitian (RD) order-writing privileges on appropriate PN use has yet to be reported. A retrospective cohort was conducted at a single tertiary care urban academic medical center to compare adult PN use before RD order-writing privileges (January 1, 2003 to December 31, 2004, pre-privileges) to after RD order-writing privileges (January 1, 2006 to December 31, 2007, post-privileges). RD order-writing privileges were obtained June 2005; PN patients during the washout period (January 1, 2005 to December 31, 2005) were not included. Descriptive statistics were conducted (N=1,965 patients). Although total hospital admissions increased from the pre-privileges to post-privileges periods (P<0.0001), overall PN use decreased from 1,080 patients during the pre-privileges period to 885 patients during the post-privileges period (P<0.0001). Inappropriate PN use decreased from 482 (45%) to 240 (27%) patients (P<0.0001) during the pre- and post-privileges periods, respectively. Among inappropriate PN use, there was a decrease in PN administration for patients with poor oral intake (130 to 41 patients), pancreatitis (78 to 26 patients), intractable nausea and vomiting (68 to 23 patients), and mucositis (56 to 18 patients; all Ps<0.0003), reflecting a 20% cost savings for PN. No significant differences were found in hospital length of stay, admissions to intensive care units, or other infectious complications between the two periods. RDs with order-writing privileges can decrease inappropriate PN use and costs in a hospital setting. Future studies should continue to highlight the influence of RDs in these advanced practice roles, as well as other members of the nutrition support team, especially with regard to nutrition support delivery and patient outcomes.

Efficacy and Safety of Tranexamic Acid Versus ϵ-Aminocaproic Acid in Cardiovascular Surgery

Background: Blood conservation is a major concern in the management of surgical patients because of transfusion-related complications, limited supply, and health care costs. Tranexamic acid (TXA) and ϵ-aminocaproic acid (ϵACA) are lysine analogue antifibrinolytics used to reduce surgical bleeding and transfusions. Objective: To evaluate the efficacy and safety of TXA compared with ϵACA in the management of cardiovascular surgical bleeding at an academic medical center. Methods: This single-center, retrospective, observational cohort study included 120 patients undergoing cardiovascular surgery with or without cardiopulmonary bypass, who received at least 1 dose of perioperative TXA or ϵACA. The efficacy outcome—massive perioperative bleeding—was a composite end point of chest tube drainage >1500 mL in any 8-hour period after surgery, perioperative transfusion of 10 or more units of packed red blood cells, reoperation for bleeding, or death from hemorrhage within 30 days. The safety outcomes were incidence of thromboembolic events, postoperative renal dysfunction, seizure, and 30-day all-cause mortality. Results: The primary end point—massive perioperative bleeding—occurred in 10 patients (16.7%) in the TXA group compared with 5 patients (8.3%) in the ϵACA group (P = 0.17). There were no significant differences in the secondary end points of 30-day all-cause mortality, thromboembolic events, renal dysfunction, and seizure. Conclusions: There were no differences in the efficacy and safety outcomes between TXA and ϵACA in the management of cardiovascular surgical bleeding at our institution. Considering the substantial cost difference and comparable efficacy and safety, ϵACA may have better value over TXA for reducing cardiovascular surgical bleeding.