We sought to systematically review and meta-analyze the available data on the association between timing of antibiotic administration and mortality in severe sepsis and septic shock.
A comprehensive ...search criteria was performed using a predefined protocol.
adult patients with severe sepsis or septic shock, reported time to antibiotic administration in relation to emergency department triage and/or shock recognition, and mortality.
immunosuppressed populations, review article, editorial, or nonhuman studies.
Two reviewers screened abstracts with a third reviewer arbitrating. The effect of time to antibiotic administration on mortality was based on current guideline recommendations: 1) administration within 3 hours of emergency department triage and 2) administration within 1 hour of severe sepsis/septic shock recognition. Odds ratios were calculated using a random effect model. The primary outcome was mortality.
A total of 1,123 publications were identified and 11 were included in the analysis. Among the 11 included studies, 16,178 patients were evaluable for antibiotic administration from emergency department triage. Patients who received antibiotics more than 3 hours after emergency department triage (< 3 hr reference) had a pooled odds ratio for mortality of 1.16 (0.92-1.46; p = 0.21). A total of 11,017 patients were evaluable for antibiotic administration from severe sepsis/septic shock recognition. Patients who received antibiotics more than 1 hour after severe sepsis/shock recognition (< 1 hr reference) had a pooled odds ratio for mortality of 1.46 (0.89-2.40; p = 0.13). There was no increased mortality in the pooled odds ratios for each hourly delay from less than 1 to more than 5 hours in antibiotic administration from severe sepsis/shock recognition.
Using the available pooled data, we found no significant mortality benefit of administering antibiotics within 3 hours of emergency department triage or within 1 hour of shock recognition in severe sepsis and septic shock. These results suggest that currently recommended timing metrics as measures of quality of care are not supported by the available evidence.
The Third International Consensus Definitions Task Force (Sepsis-3) recently recommended changes to the definitions of sepsis. The impact of these changes remains unclear. Our objective was to ...determine the outcomes of patients meeting Sepsis-3 septic shock criteria versus patients meeting the "old" (1991) criteria of septic shock only.
Secondary analysis of two clinical trials of early septic shock resuscitation.
Large academic emergency departments in the United States.
Patients with suspected infection, more than or equal to two systemic inflammatory response syndrome criteria, and systolic blood pressure less than 90 mm Hg after fluid resuscitation.
Patients were further categorized as Sepsis-3 septic shock if they demonstrated hypotension, received vasopressors, and exhibited a lactate greater than 2 mmol/L. We compared in-hospital mortality in patients who met the old definition only with those who met the Sepsis-3 criteria.
Four hundred seventy patients were included in the present analysis. Two hundred (42.5%) met Sepsis-3 criteria, whereas 270 (57.4%) met only the old definition. Patients meeting Sepsis-3 criteria demonstrated higher severity of illness by Sequential Organ Failure Assessment score (9 vs 5; p < 0.001) and mortality (29% vs 14%; p < 0.001). Subgroup analysis of 127 patients meeting only the old definition demonstrated significant mortality benefit following implementation of a quantitative resuscitation protocol (35% vs 10%; p = 0.006).
In this analysis, 57% of patients meeting old definition for septic shock did not meet Sepsis-3 criteria. Although Sepsis-3 criteria identified a group of patients with increased organ failure and higher mortality, those patients who met the old criteria and not Sepsis-3 criteria still demonstrated significant organ failure and 14% mortality rate.
Organ failure worsens outcome in sepsis. The Sequential Organ Failure Assessment (SOFA) score numerically quantifies the number and severity of failed organs. We examined the utility of the SOFA ...score for assessing outcome of patients with severe sepsis with evidence of hypoperfusion at the time of emergency department (ED) presentation.
Prospective observational study.
Urban, tertiary ED with an annual census of >110,000.
ED patients with severe sepsis with evidence of hypoperfusion.
suspected infection, two or more criteria of systemic inflammation, and either systolic blood pressure <90 mm Hg after a fluid bolus or lactate >or=4 mmol/L.
age <18 years or need for immediate surgery.
SOFA scores were calculated at ED recognition (T0) and 72 hours after intensive care unit admission (T72). The primary outcome was in-hospital mortality. The area under the receiver operating characteristic curve was used to evaluate the predictive ability of SOFA scores at each time point. The relationship between Delta SOFA (change in SOFA from T0 to T72) was examined for linearity.
A total of 248 subjects aged 57 +/- 16 years, 48% men, were enrolled over 2 years. All patients were treated with a standardized quantitative resuscitation protocol; the in-hospital mortality rate was 21%. The mean SOFA score at T0 was 7.1 +/- 3.6 points and at T72 was 7.4 +/- 4.9 points. The area under the receiver operating characteristic curve of SOFA for predicting in-hospital mortality at T0 was 0.75 (95% confidence interval 0.68-0.83) and at T72 was 0.84 (95% confidence interval 0.77-0.90). The Delta SOFA was found to have a positive relationship with in-hospital mortality.
The SOFA score provides potentially valuable prognostic information on in-hospital survival when applied to patients with severe sepsis with evidence of hypoperfusion at the time of ED presentation.
Abstract Background We sought to compare the association of whole-blood lactate kinetics with survival in patients with septic shock undergoing early quantitative resuscitation. Methods This was a ...preplanned analysis of a multicenter, ED-based, randomized, controlled trial of early sepsis resuscitation. Inclusion criteria were suspected infection, two or more systemic inflammation criteria, either systolic BP< 90 mm Hg after a fluid bolus or lactate level > 4 mM, two serial lactate measurements, and an initial lactate level > 2.0 mM. We calculated the relative lactate clearance, rate of lactate clearance, and occurrence of early lactate normalization (decline to < 2.0 mM in the first 6 h). Area under the receiver operating characteristic curve (AUC) and multivariate logistic regression were used to determine the lactate kinetic parameters that were the strongest predictors of survival. Results The analysis included 187 patients, of whom 36% (n = 68) normalized their lactate level. Overall survival was 76.5% (143 of 187 patients), and the AUC of initial lactate to predict survival was 0.64. The AUCs for relative lactate clearance and lactate clearance rate were 0.67 and 0.58, respectively. Lactate normalization was the strongest predictor of survival (adjusted OR, 5.2; 95% CI, 1.7–15.8), followed by lactate clearance ≥ 50% (OR, 4.0; 95% CI, 1.6–10.0). Lactate clearance ≥ 10% (OR, 1.6; 95% CI, 0.6–4.4) was not a significant independent predictor in this cohort. Conclusions In patients in the ED with a sepsis diagnosis, early lactate normalization during the first 6 h of resuscitation was the strongest independent predictor of survival and was superior to other measures of lactate kinetics. Trial registry ClinicalTrials.gov ; No.: NCT00372502 ; URL: clinicaltrials.gov
To prospectively validate that the inability to decrease procalcitonin levels by more than 80% between baseline and day 4 is associated with increased 28-day all-cause mortality in a large sepsis ...patient population recruited across the United States.
Blinded, prospective multicenter observational clinical trial following an Food and Drug Administration-approved protocol.
Thirteen U.S.-based emergency departments and ICUs.
Consecutive patients meeting criteria for severe sepsis or septic shock who were admitted to the ICU from the emergency department, other wards, or directly from out of hospital were included.
Procalcitonin was measured daily over the first 5 days.
The primary analysis of interest was the relationship between a procalcitonin decrease of more than 80% from baseline to day 4 and 28-day mortality using Cox proportional hazards regression. Among 858 enrolled patients, 646 patients were alive and in the hospital on day 4 and included in the main intention-to-diagnose analysis. The 28-day all-cause mortality was two-fold higher when procalcitonin did not show a decrease of more than 80% from baseline to day 4 (20% vs 10%; p = 0.001). This was confirmed as an independent predictor in Cox regression analysis (hazard ratio, 1.97 95% CI, 1.18-3.30; p < 0.009) after adjusting for demographics, Acute Physiology and Chronic Health Evaluation II, ICU residence on day 4, sepsis syndrome severity, antibiotic administration time, and other relevant confounders.
Results of this large, prospective multicenter U.S. study indicate that inability to decrease procalcitonin by more than 80% is a significant independent predictor of mortality and may aid in sepsis care.
Partial pressure of arterial carbon dioxide (PaCO2) is a regulator of cerebral blood flow after brain injury. We sought to test the association between PaCO2 after resuscitation from cardiac arrest ...and neurological outcome.
A prospective protocol-directed cohort study across six hospitals. Inclusion criteria: age ≥18, non-traumatic cardiac arrest, mechanically ventilated after return of spontaneous circulation (ROSC), and receipt of targeted temperature management. Per protocol, PaCO2 was measured by arterial blood gas analyses at one and six hours after ROSC. We determined the mean PaCO2 over this initial six hours after ROSC. The primary outcome was good neurological function at hospital discharge, defined a priori as a modified Rankin Scale ≤3. Multivariable Poisson regression analysis was used to test the association between PaCO2 and neurological outcome.
Of the 280 patients included, the median (interquartile range) PaCO2 was 44 (37–52) mmHg and 30% had good neurological function. We found mean PaCO2 had a quadratic (inverted “U” shaped) association with good neurological outcome, with a mean PaCO2 of 68 mmHg having the highest predictive probability of good neurological outcome, and worse neurological outcome at higher and lower PaCO2. Presence of metabolic acidosis attenuated the association between PaCO2 and good neurological outcome, with a PaCO2 of 51 mmHg having the highest predictive probability of good neurological outcome among patients with metabolic acidosis.
PaCO2 has a “U” shaped association with neurological outcome, with mild to moderate hypercapnia having the highest probability of good neurological outcome.
Laboratory and recent clinical data suggest that hyperoxemia after resuscitation from cardiac arrest is harmful; however, it remains unclear if the risk of adverse outcome is a threshold effect at a ...specific supranormal oxygen tension, or is a dose-dependent association. We aimed to define the relationship between supranormal oxygen tension and outcome in postresuscitation patients.
This was a multicenter cohort study using the Project IMPACT database (intensive care units at 120 US hospitals). Inclusion criteria were age >17 years, nontrauma, cardiopulmonary resuscitation preceding intensive care unit arrival, and postresuscitation arterial blood gas obtained. We excluded patients with hypoxia or severe oxygenation impairment. We defined the exposure by the highest partial pressure of arterial oxygen (PaO(2)) over the first 24 hours in the ICU. The primary outcome measure was in-hospital mortality. We tested the association between PaO(2) (continuous variable) and mortality using multivariable logistic regression adjusted for patient-oriented covariates and potential hospital effects. Of 4459 patients, 54% died. The median postresuscitation PaO(2) was 231 (interquartile range 149 to 349) mm Hg. Over ascending ranges of oxygen tension, we found significant linear trends of increasing in-hospital mortality and decreasing survival as functionally independent. On multivariable analysis, a 100 mm Hg increase in PaO(2) was associated with a 24% increase in mortality risk (odds ratio 1.24 95% confidence interval 1.18 to 1.31. We observed no evidence supporting a single threshold for harm from supranormal oxygen tension.
In this large sample of postresuscitation patients, we found a dose-dependent association between supranormal oxygen tension and risk of in-hospital death.
Abstract
Low-molecular-weight organic compounds in root exudates play a key role in plant–microorganism interactions by influencing the structure and function of soil microbial communities. Model ...exudate solutions, based on organic acids (OAs) (quinic, lactic, maleic acids) and sugars (glucose, sucrose, fructose), previously identified in the rhizosphere of Pinus radiata, were applied to soil microcosms. Root exudate compound solutions stimulated soil dehydrogenase activity and the addition of OAs increased soil pH. The structure of active bacterial communities, based on reverse-transcribed 16S rRNA gene PCR, was assessed by denaturing gradient gel electrophoresis and PhyloChip microarrays. Bacterial taxon richness was greater in all treatments than that in control soil, with a wide range of taxa (88–1043) responding positively to exudate solutions and fewer (<24) responding negatively. OAs caused significantly greater increases than sugars in the detectable richness of the soil bacterial community and larger shifts of dominant taxa. The greater response of bacteria to OAs may be due to the higher amounts of added carbon, solubilization of soil organic matter or shifts in soil pH. Our results indicate that OAs play a significant role in shaping soil bacterial communities and this may therefore have a significant impact on plant growth.
Guidelines for post-cardiac arrest care recommend blood pressure optimization as one component of neuroprotection. Although some retrospective clinical studies suggest that postresuscitation ...hypotension may be harmful, and laboratory studies suggest that a postresuscitation hypertensive surge may be protective, empirical data are few. In this study, we prospectively measured blood pressure over time during the postresuscitation period and tested its association with neurologic outcome.
Single center, prospective observational study from 2009 to 2012.
Inclusion criteria were age 18 years old or older, prearrest independent functional status, resuscitation from cardiac arrest, and comatose immediately after resuscitation.
Our research protocol measured blood pressure noninvasively every 15 minutes for the first 6 hours after resuscitation. We calculated the 0- to 6-hour time-weighted average mean arterial pressure and used multivariable logistic regression to test the association between increasing time-weighted average mean arterial pressures and good neurologic outcome, defined as Cerebral Performance Category 1 or 2 at hospital discharge. Among 151 patients, 44 (29%) experienced good neurologic outcome. The association between blood pressure and outcome appears to have a threshold effect at time-weighted average mean arterial pressure value of 70 mm Hg. This threshold (mean arterial pressure > 70 mm Hg) had the strongest association with good neurologic outcome (odds ratio, 4.11; 95% CI, 1.34-12.66; p = 0.014). A sustained intrinsic hypertensive surge was relatively uncommon and was not associated with neurologic outcome.
We found that time-weighted average mean arterial pressure was associated with good neurologic outcome at a threshold of mean arterial pressure greater than 70 mm Hg.
High density lipoprotein (HDL) is important for defense against sepsis but becomes dysfunctional (Dys-HDL) during inflammation. We hypothesize that Dys-HDL correlates with organ dysfunction ...(sequential organ failure assessment (SOFA) score) early sepsis.
A prospective cohort study of adult ED sepsis patients enrolled within 24 hours.
Eighty eight patients were analyzed. Dys-HDL (expressed as HDL inflammatory index (HII)) correlated with SOFA at enrollment (r = 0.23, p = 0.024) and at 48 hours (r = 0.24, p = 0.026) but HII change over the first 48 hours did not correlate with change in SOFA (r = 0.06, p = 0.56). Enrollment HII was significantly different in patients with most severe organ failure (2.31, IQR 1.33-5.2) compared to less severe organ failure (1.81, IQR 1.23-2.64, p = 0.043). Change in HII over 48 hours was significantly different for in-hospital non-survivors (-0.45, IQR-2.6, -0.14 p = 0.015) and for 28-day non-survivors (-1.12, IQR -1.52, 0.12, p = 0.044). In a multivariable linear regression equation (R2 = 0.13), for each unit HII increase, 48-hour SOFA increased by 0.72 (p = 0.009).
HII correlated with SOFA and predicted 48-hour SOFA score in early sepsis. Future studies are needed to delineate potential mechanisms.
NCT02370186. Registered February 24, 2015.
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