Increased Time to Initial Antimicrobial Administration Is Associated With Progression to Septic Shock in Severe Sepsis Patients
Whiles, B et al
Critical Care Medicine: April 2017 - Volume 45 - Issue 4 - p 623–629
Objectives: To determine if time to initial antimicrobial is associated with progression of severe sepsis to septic shock. Design: Retrospective cohort. Setting: Six hundred fifty-six bed urban academic medical center. Patients: Emergency department patients greater than or equal to 18 years old with severe sepsis and/or septic shock and antimicrobial administration within 24 hours. Patients with shock on presentation were excluded. Interventions: Not available.
Measurements and Main Results: We identified 3,929 severe sepsis patients, with overall mortality 12.8%. Nine hundred eighty-four patients (25.0%) progressed to septic shock. The median time to antimicrobial was 3.77 hours (interquartile range = 1.96–6.42) in those who progressed versus 2.76 hours (interquartile range = 1.60–4.82) in those who did not (p < 0.001). Multivariate logistic regression demonstrated that male sex (odds ratio = 1.18; 95% CI, 1.01–1.36), Charlson Comorbidity Index (odds ratio = 1.18; 95% CI, 1.11–1.27), number of infections (odds ratio = 1.05; 95% CI, 1.02–1.08), and time to first antimicrobial (odds ratio = 1.08; 95% CI, 1.06–1.10) were associated with progression. Each hour until initial antimicrobial administration was associated with a 8.0% increase in progression to septic shock. Additionally, time to broad-spectrum antimicrobial was associated with progression (odds ratio = 1.06; 95% CI, 1.05–1.08). Time to initial antimicrobial was also associated with in-hospital mortality (odds ratio = 1.05; 95% CI, 1.03–1.07).
Conclusions: This study emphasizes the importance of early, broad-spectrum antimicrobial administration in severe sepsis patients admitted through the emergency department, as longer time to initial antimicrobial administration is associated with increased progression of severe sepsis to septic shock and increased mortality.
Thursday, 13 April 2017
Fever in the Emergency Department Predicts Survival of Patients With Severe Sepsis and Septic Shock Admitted to the ICU
Fever in the Emergency Department Predicts Survival of Patients With Severe Sepsis and Septic Shock Admitted to the ICU
Sundén-Cullberg, J et al
Critical Care Medicine: April 2017 - Volume 45 - Issue 4 - p 591–599
Objectives: To study the prognostic value of fever in the emergency department in septic patients subsequently admitted to the ICU. Design: Observational cohort study from the Swedish national quality register for sepsis. Setting: Thirty ICU’s in Sweden. Patients: Two thousand two hundred twenty-five adults who were admitted to an ICU within 24 hours of hospital arrival with a diagnosis of severe sepsis or septic shock were included. Interventions: None.
Measurements and Main Results: Body temperature was measured and classified according to four categories (< 37°C, 37–38.29°C, 38.3–39.5°C, ≥ 39.5°C). The main outcome was in-hospital mortality. Odds ratios for mortality according to body temperature were estimated using multivariable logistic regression. Subgroup analyses were conducted according to age, sex, underlying comorbidity, and time to given antibiotics. Overall mortality was 25%. More than half of patients had a body temperature below 38.3°C. Mortality was inversely correlated with temperature and decreased, on average, more than 5% points per °C increase, from 50% in those with the lowest temperatures to 9% in those with the highest. Increased body temperature in survivors was also associated with shorter hospital stays. Patients with fever received better quality of care, but the inverse association between body temperature and mortality was robust and remained consistent after adjustment for quality of care measures and other factors that could have confounded the association. Among vital signs, body temperature was best at predicting mortality.
Conclusions: Contrary to common perceptions and current guidelines for care of critically ill septic patients, increased body temperature in the emergency department was strongly associated with lower mortality and shorter hospital stays in patients with severe sepsis or septic shock subsequently admitted to the ICU.
Sundén-Cullberg, J et al
Critical Care Medicine: April 2017 - Volume 45 - Issue 4 - p 591–599
Objectives: To study the prognostic value of fever in the emergency department in septic patients subsequently admitted to the ICU. Design: Observational cohort study from the Swedish national quality register for sepsis. Setting: Thirty ICU’s in Sweden. Patients: Two thousand two hundred twenty-five adults who were admitted to an ICU within 24 hours of hospital arrival with a diagnosis of severe sepsis or septic shock were included. Interventions: None.
Measurements and Main Results: Body temperature was measured and classified according to four categories (< 37°C, 37–38.29°C, 38.3–39.5°C, ≥ 39.5°C). The main outcome was in-hospital mortality. Odds ratios for mortality according to body temperature were estimated using multivariable logistic regression. Subgroup analyses were conducted according to age, sex, underlying comorbidity, and time to given antibiotics. Overall mortality was 25%. More than half of patients had a body temperature below 38.3°C. Mortality was inversely correlated with temperature and decreased, on average, more than 5% points per °C increase, from 50% in those with the lowest temperatures to 9% in those with the highest. Increased body temperature in survivors was also associated with shorter hospital stays. Patients with fever received better quality of care, but the inverse association between body temperature and mortality was robust and remained consistent after adjustment for quality of care measures and other factors that could have confounded the association. Among vital signs, body temperature was best at predicting mortality.
Conclusions: Contrary to common perceptions and current guidelines for care of critically ill septic patients, increased body temperature in the emergency department was strongly associated with lower mortality and shorter hospital stays in patients with severe sepsis or septic shock subsequently admitted to the ICU.
Diagnostic Accuracy of Central Venous Catheter Confirmation by Bedside Ultrasound Versus Chest Radiography in Critically Ill Patients: A Systematic Review and Meta-Analysis
Diagnostic Accuracy of Central Venous Catheter Confirmation by Bedside Ultrasound Versus Chest Radiography in Critically Ill Patients: A Systematic Review and Meta-Analysis
Ablordeppey, E et al
Critical Care Medicine: April 2017 - Volume 45 - Issue 4 - p 715–724
Objective: We performed a systematic review and meta-analysis to examine the accuracy of bedside ultrasound for confirmation of central venous catheter position and exclusion of pneumothorax compared with chest radiography. Data Sources: PubMed, Embase, Cochrane Central Register of Controlled Trials, reference lists, conference proceedings and ClinicalTrials.gov . Study Selection: Articles and abstracts describing the diagnostic accuracy of bedside ultrasound compared with chest radiography for confirmation of central venous catheters in sufficient detail to reconstruct 2 × 2 contingency tables were reviewed. Primary outcomes included the accuracy of confirming catheter positioning and detecting a pneumothorax. Secondary outcomes included feasibility, interrater reliability, and efficiency to complete bedside ultrasound confirmation of central venous catheter position.
Data Extraction: Investigators abstracted study details including research design and sonographic imaging technique to detect catheter malposition and procedure-related pneumothorax. Diagnostic accuracy measures included pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio.
Data Synthesis: Fifteen studies with 1,553 central venous catheter placements were identified with a pooled sensitivity and specificity of catheter malposition by ultrasound of 0.82 (0.77–0.86) and 0.98 (0.97–0.99), respectively. The pooled positive and negative likelihood ratios of catheter malposition by ultrasound were 31.12 (14.72–65.78) and 0.25 (0.13–0.47). The sensitivity and specificity of ultrasound for pneumothorax detection was nearly 100% in the participating studies. Bedside ultrasound reduced mean central venous catheter confirmation time by 58.3 minutes. Risk of bias and clinical heterogeneity in the studies were high.
Conclusions: Bedside ultrasound is faster than radiography at identifying pneumothorax after central venous catheter insertion. When a central venous catheter malposition exists, bedside ultrasound will identify four out of every five earlier than chest radiography.
Ablordeppey, E et al
Critical Care Medicine: April 2017 - Volume 45 - Issue 4 - p 715–724
Objective: We performed a systematic review and meta-analysis to examine the accuracy of bedside ultrasound for confirmation of central venous catheter position and exclusion of pneumothorax compared with chest radiography. Data Sources: PubMed, Embase, Cochrane Central Register of Controlled Trials, reference lists, conference proceedings and ClinicalTrials.gov . Study Selection: Articles and abstracts describing the diagnostic accuracy of bedside ultrasound compared with chest radiography for confirmation of central venous catheters in sufficient detail to reconstruct 2 × 2 contingency tables were reviewed. Primary outcomes included the accuracy of confirming catheter positioning and detecting a pneumothorax. Secondary outcomes included feasibility, interrater reliability, and efficiency to complete bedside ultrasound confirmation of central venous catheter position.
Data Extraction: Investigators abstracted study details including research design and sonographic imaging technique to detect catheter malposition and procedure-related pneumothorax. Diagnostic accuracy measures included pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio.
Data Synthesis: Fifteen studies with 1,553 central venous catheter placements were identified with a pooled sensitivity and specificity of catheter malposition by ultrasound of 0.82 (0.77–0.86) and 0.98 (0.97–0.99), respectively. The pooled positive and negative likelihood ratios of catheter malposition by ultrasound were 31.12 (14.72–65.78) and 0.25 (0.13–0.47). The sensitivity and specificity of ultrasound for pneumothorax detection was nearly 100% in the participating studies. Bedside ultrasound reduced mean central venous catheter confirmation time by 58.3 minutes. Risk of bias and clinical heterogeneity in the studies were high.
Conclusions: Bedside ultrasound is faster than radiography at identifying pneumothorax after central venous catheter insertion. When a central venous catheter malposition exists, bedside ultrasound will identify four out of every five earlier than chest radiography.
Angioedema
Angioedema
LoVerde, D et al
Critical Care Medicine: April 2017 - Volume 45 - Issue 4 - p 725–735
Objectives: Angioedema is a potentially life-threatening occurrence that is encountered by critical care providers. The mechanistic understanding of angioedema syndromes has improved in recent years, and novel medications are available that improve outcomes from these syndromes. This clinically focused review will describe the underlying genetics, pathophysiology, classification and treatment of angioedema syndromes, with an emphasis on the novel pharmacologic agents that have recently become available for acute treatment.
Data Sources: A MEDLINE search was conducted with the MeSH terms angioedema, acquired angioedema, hereditary angioedema type III, and angiotensin converting enzyme inhibitor-induced angioedema.
Study Selection: Selected publications describing angioedema, clinical trials, diagnosis, management, and genetics were retrieved (reviews, guidelines, clinical trials, case series), and their bibliographies were also reviewed to identify relevant publications.
Data Extraction: Data from the relevant publications were reviewed, summarized and the information synthesized.
Data Synthesis: The data obtained were used to describe the current state of diagnosis and management of various angioedema syndromes.
Conclusions: Angioedema is a life-threatening syndrome with multiple subtypes, each with a distinct pathophysiology. We present an evidence-based approach to the diagnosis and suggested management of various subtypes of angioedema. Securing the airway remains the most important intervention, followed by administration of both established and more novel pharmacologic interventions based on disease pathology.
LoVerde, D et al
Critical Care Medicine: April 2017 - Volume 45 - Issue 4 - p 725–735
Objectives: Angioedema is a potentially life-threatening occurrence that is encountered by critical care providers. The mechanistic understanding of angioedema syndromes has improved in recent years, and novel medications are available that improve outcomes from these syndromes. This clinically focused review will describe the underlying genetics, pathophysiology, classification and treatment of angioedema syndromes, with an emphasis on the novel pharmacologic agents that have recently become available for acute treatment.
Data Sources: A MEDLINE search was conducted with the MeSH terms angioedema, acquired angioedema, hereditary angioedema type III, and angiotensin converting enzyme inhibitor-induced angioedema.
Study Selection: Selected publications describing angioedema, clinical trials, diagnosis, management, and genetics were retrieved (reviews, guidelines, clinical trials, case series), and their bibliographies were also reviewed to identify relevant publications.
Data Extraction: Data from the relevant publications were reviewed, summarized and the information synthesized.
Data Synthesis: The data obtained were used to describe the current state of diagnosis and management of various angioedema syndromes.
Conclusions: Angioedema is a life-threatening syndrome with multiple subtypes, each with a distinct pathophysiology. We present an evidence-based approach to the diagnosis and suggested management of various subtypes of angioedema. Securing the airway remains the most important intervention, followed by administration of both established and more novel pharmacologic interventions based on disease pathology.
Sodium Bicarbonate Versus Sodium Chloride for Preventing Contrast-Associated Acute Kidney Injury in Critically Ill Patients: A Randomized Controlled Trial
Sodium Bicarbonate Versus Sodium Chloride for Preventing Contrast-Associated Acute Kidney Injury in Critically Ill Patients: A Randomized Controlled Trial
Valette, X et al
Critical Care Medicine: April 2017 - Volume 45 - Issue 4 - p 637–644
Objectives: To test whether hydration with bicarbonate rather than isotonic sodium chloride reduces the risk of contrast-associated acute kidney injury in critically ill patients. Design: Prospective, double-blind, multicenter, randomized controlled study.
Setting: Three French ICUs. Patients: Critically ill patients with stable renal function (n = 307) who received intravascular contrast media. Interventions: Hydration with 0.9% sodium chloride or 1.4% sodium bicarbonate administered with the same infusion protocol: 3 mL/kg during 1 hour before and 1 mL/kg/hr during 6 hours after contrast medium exposure.
Measurements and Main Results: The primary endpoint was the development of contrast-associated acute kidney injury, as defined by the Acute Kidney Injury Network criteria, 72 hours after contrast exposure. Patients randomized to the bicarbonate group (n = 151) showed a higher urinary pH at the end of the infusion than patients randomized to the saline group (n = 156) (6.7 ± 2.1 vs 6.2 ± 1.8, respectively; p < 0.0001). The frequency of contrast-associated acute kidney injury was similar in both groups: 52 patients (33.3%) in the saline group and 53 patients (35.1%) in the bicarbonate group (absolute risk difference, –1.8%; 95% CI [–12.3% to 8.9%]; p = 0.81). The need for renal replacement therapy (five [3.2%] and six [3.9%] patients; p = 0.77), ICU length of stay (24.7 ± 22.9 and 23 ± 23.8 d; p = 0.52), and mortality (25 [16.0%] and 24 [15.9%] patients; p > 0.99) were also similar between the saline and bicarbonate groups, respectively.
Conclusions: Except for urinary pH, none of the outcomes differed between the two groups. Among ICU patients with stable renal function, the benefit of using sodium bicarbonate rather than isotonic sodium chloride for preventing contrast-associated acute kidney injury is marginal, if any.
Valette, X et al
Critical Care Medicine: April 2017 - Volume 45 - Issue 4 - p 637–644
Objectives: To test whether hydration with bicarbonate rather than isotonic sodium chloride reduces the risk of contrast-associated acute kidney injury in critically ill patients. Design: Prospective, double-blind, multicenter, randomized controlled study.
Setting: Three French ICUs. Patients: Critically ill patients with stable renal function (n = 307) who received intravascular contrast media. Interventions: Hydration with 0.9% sodium chloride or 1.4% sodium bicarbonate administered with the same infusion protocol: 3 mL/kg during 1 hour before and 1 mL/kg/hr during 6 hours after contrast medium exposure.
Measurements and Main Results: The primary endpoint was the development of contrast-associated acute kidney injury, as defined by the Acute Kidney Injury Network criteria, 72 hours after contrast exposure. Patients randomized to the bicarbonate group (n = 151) showed a higher urinary pH at the end of the infusion than patients randomized to the saline group (n = 156) (6.7 ± 2.1 vs 6.2 ± 1.8, respectively; p < 0.0001). The frequency of contrast-associated acute kidney injury was similar in both groups: 52 patients (33.3%) in the saline group and 53 patients (35.1%) in the bicarbonate group (absolute risk difference, –1.8%; 95% CI [–12.3% to 8.9%]; p = 0.81). The need for renal replacement therapy (five [3.2%] and six [3.9%] patients; p = 0.77), ICU length of stay (24.7 ± 22.9 and 23 ± 23.8 d; p = 0.52), and mortality (25 [16.0%] and 24 [15.9%] patients; p > 0.99) were also similar between the saline and bicarbonate groups, respectively.
Conclusions: Except for urinary pH, none of the outcomes differed between the two groups. Among ICU patients with stable renal function, the benefit of using sodium bicarbonate rather than isotonic sodium chloride for preventing contrast-associated acute kidney injury is marginal, if any.
Meta-Analysis of Therapeutic Hypothermia for Traumatic Brain Injury in Adult and Pediatric Patients
Meta-Analysis of Therapeutic Hypothermia for Traumatic Brain Injury in Adult and Pediatric Patients
Crompton, E et al
Critical Care Medicine: April 2017 - Volume 45 - Issue 4 - p 575–583
Objective: Therapeutic hypothermia has been used to attenuate the effects of traumatic brain injuries. However, the required degree of hypothermia, length of its use, and its timing are uncertain. We undertook a comprehensive meta-analysis to quantify benefits of hypothermia therapy for traumatic brain injuries in adults and children by analyzing mortality rates, neurologic outcomes, and adverse effects. Data Sources: Electronic databases PubMed, Google Scholar, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov and manual searches of studies were conducted for relevant publications up until February 2016.
Study Selection: Forty-one studies in adults (n = 3,109; age range, 18–81 yr) and eight studies in children (n = 454; age range, 3 mo to 18 yr) met eligibility criteria. Data Extraction: Baseline patient characteristics, enrollment time, methodology of cooling, target temperature, duration of hypothermia, and rewarming protocols were extracted. Data Synthesis: Risk ratios with 95% CIs were calculated. Compared with adults who were kept normothermic, those who underwent therapeutic hypothermia were associated with 18% reduction in mortality (risk ratio, 0.82; 95% CI, 0.70–0.96; p = 0.01) and a 35% improvement in neurologic outcome (risk ratio, 1.35; 95% CI, 1.18–1.54; p < 0.00001). The optimal management strategy for adult patients included cooling patients to a minimum of 33°C for 72 hours, followed by spontaneous, natural rewarming. In contrast, adverse outcomes were observed in children who underwent hypothermic treatment with a 66% increase in mortality (risk ratio, 1.66; 95% CI, 1.06–2.59; p = 0.03) and a marginal deterioration of neurologic outcome (risk ratio, 0.90; 95% CI, 0.80–1.01; p = 0.06).
Conclusions: Therapeutic hypothermia is likely a beneficial treatment following traumatic brain injuries in adults but cannot be recommended in children.
Crompton, E et al
Critical Care Medicine: April 2017 - Volume 45 - Issue 4 - p 575–583
Objective: Therapeutic hypothermia has been used to attenuate the effects of traumatic brain injuries. However, the required degree of hypothermia, length of its use, and its timing are uncertain. We undertook a comprehensive meta-analysis to quantify benefits of hypothermia therapy for traumatic brain injuries in adults and children by analyzing mortality rates, neurologic outcomes, and adverse effects. Data Sources: Electronic databases PubMed, Google Scholar, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov and manual searches of studies were conducted for relevant publications up until February 2016.
Study Selection: Forty-one studies in adults (n = 3,109; age range, 18–81 yr) and eight studies in children (n = 454; age range, 3 mo to 18 yr) met eligibility criteria. Data Extraction: Baseline patient characteristics, enrollment time, methodology of cooling, target temperature, duration of hypothermia, and rewarming protocols were extracted. Data Synthesis: Risk ratios with 95% CIs were calculated. Compared with adults who were kept normothermic, those who underwent therapeutic hypothermia were associated with 18% reduction in mortality (risk ratio, 0.82; 95% CI, 0.70–0.96; p = 0.01) and a 35% improvement in neurologic outcome (risk ratio, 1.35; 95% CI, 1.18–1.54; p < 0.00001). The optimal management strategy for adult patients included cooling patients to a minimum of 33°C for 72 hours, followed by spontaneous, natural rewarming. In contrast, adverse outcomes were observed in children who underwent hypothermic treatment with a 66% increase in mortality (risk ratio, 1.66; 95% CI, 1.06–2.59; p = 0.03) and a marginal deterioration of neurologic outcome (risk ratio, 0.90; 95% CI, 0.80–1.01; p = 0.06).
Conclusions: Therapeutic hypothermia is likely a beneficial treatment following traumatic brain injuries in adults but cannot be recommended in children.
Bedside Glucose Monitoring—Is it Safe? A New, Regulatory-Compliant Risk Assessment Evaluation Protocol in Critically Ill Patient Care Settings*
Bedside Glucose Monitoring Is it Safe? A New, Regulatory-Compliant Risk Assessment Evaluation Protocol in Critically Ill Patient Care Settings
DuBois, J et al
Critical Care Medicine: April 2017 - Volume 45 - Issue 4 - p 567–574
Objectives: New data have emerged from ambulatory and acute care settings about adverse patient events, including death, attributable to erroneous blood glucose meter measurements and leading to questions over their use in critically ill patients. The U.S. Food and Drug Administration published new, more stringent guidelines for glucose meter manufacturers to evaluate the performance of blood glucose meters in critically ill patient settings. The primary objective of this international, multicenter, multidisciplinary clinical study was to develop and apply a rigorous clinical accuracy assessment algorithm, using four distinct statistical tools, to evaluate the clinical accuracy of a blood glucose monitoring system in critically ill patients.
Design: Observational study. Setting: Five international medical and surgical ICUs. Patients: All patients admitted to critical care settings in the centers. Interventions: None. Measurements and Main Results: Glucose measurements were performed on 1,698 critically ill patients with 257 different clinical conditions and complex treatment regimens. The clinical accuracy assessment algorithm comprised four statistical tools to assess the performance of the study blood glucose monitoring system compared with laboratory reference methods traceable to a definitive standard. Based on POCT12-A3, the Clinical Laboratory Standards Institute standard for hospitals about hospital glucose meter procedures and performance, and Parkes error grid clinical accuracy performance criteria, no clinically significant differences were observed due to patient condition or therapy, with 96.1% and 99.3% glucose results meeting the respective criteria. Stratified sensitivity and specificity analysis (10 mg/dL glucose intervals, 50–150 mg/dL) demonstrated high sensitivity (mean = 95.2%, SD = ± 0.02) and specificity (mean = 95. 8%, SD = ± 0.03). Monte Carlo simulation modeling of the study blood glucose monitoring system showed low probability of category 2 and category 3 insulin dosing error, category 2 = 2.3% (41/1,815) and category 3 = 1.8% (32/1,815), respectively. Patient trend analysis demonstrated 99.1% (223/225) concordance in characterizing hypoglycemic patients.
Conclusions: The multicomponent, clinical accuracy assessment algorithm demonstrated that the blood glucose monitoring system was acceptable for use in critically ill patient settings when compared to the central laboratory reference method. This clinical accuracy assessment algorithm is an effective tool for comprehensively assessing the validity of whole blood glucose measurement in critically ill patient care settings.
DuBois, J et al
Critical Care Medicine: April 2017 - Volume 45 - Issue 4 - p 567–574
Objectives: New data have emerged from ambulatory and acute care settings about adverse patient events, including death, attributable to erroneous blood glucose meter measurements and leading to questions over their use in critically ill patients. The U.S. Food and Drug Administration published new, more stringent guidelines for glucose meter manufacturers to evaluate the performance of blood glucose meters in critically ill patient settings. The primary objective of this international, multicenter, multidisciplinary clinical study was to develop and apply a rigorous clinical accuracy assessment algorithm, using four distinct statistical tools, to evaluate the clinical accuracy of a blood glucose monitoring system in critically ill patients.
Design: Observational study. Setting: Five international medical and surgical ICUs. Patients: All patients admitted to critical care settings in the centers. Interventions: None. Measurements and Main Results: Glucose measurements were performed on 1,698 critically ill patients with 257 different clinical conditions and complex treatment regimens. The clinical accuracy assessment algorithm comprised four statistical tools to assess the performance of the study blood glucose monitoring system compared with laboratory reference methods traceable to a definitive standard. Based on POCT12-A3, the Clinical Laboratory Standards Institute standard for hospitals about hospital glucose meter procedures and performance, and Parkes error grid clinical accuracy performance criteria, no clinically significant differences were observed due to patient condition or therapy, with 96.1% and 99.3% glucose results meeting the respective criteria. Stratified sensitivity and specificity analysis (10 mg/dL glucose intervals, 50–150 mg/dL) demonstrated high sensitivity (mean = 95.2%, SD = ± 0.02) and specificity (mean = 95. 8%, SD = ± 0.03). Monte Carlo simulation modeling of the study blood glucose monitoring system showed low probability of category 2 and category 3 insulin dosing error, category 2 = 2.3% (41/1,815) and category 3 = 1.8% (32/1,815), respectively. Patient trend analysis demonstrated 99.1% (223/225) concordance in characterizing hypoglycemic patients.
Conclusions: The multicomponent, clinical accuracy assessment algorithm demonstrated that the blood glucose monitoring system was acceptable for use in critically ill patient settings when compared to the central laboratory reference method. This clinical accuracy assessment algorithm is an effective tool for comprehensively assessing the validity of whole blood glucose measurement in critically ill patient care settings.
Early Goal-Directed Therapy for Sepsis: A Novel Solution for Discordant Survival Outcomes in Clinical Trials
Early Goal-Directed Therapy for Sepsis: A Novel Solution for Discordant Survival Outcomes in Clinical Trials
Kalil, A et al
Critical Care Medicine: April 2017 - Volume 45 - Issue 4 - p 607–614
Objectives: Early goal-directed therapy has shown discordant survival outcomes in sepsis studies. We aim to find the reasons for this discordance.
Design: Random-effects and Bayesian hierarchical analyses. Setting: Studies that evaluated early goal-directed therapy. Subjects: Patients with severe sepsis and/or septic shock. Interventions: Early goal-directed therapy.
Measurements and Main Results: A total of 19,998 patients were included in the main analysis: 31 observational (n = 15,656) and six randomized (n = 4,342) studies. The analysis from 37 studies showed that early goal-directed therapy was associated with a 23% reduction in the risk of death: relative risk = 0.77 (95% CI, 0.71–0.83); p value of less than 0.0001. Mortality reduction was seen with observational studies: relative risk = 0.73 (0.67–0.80); p value of less than 0.0001 but not with randomized studies: relative risk = 0.92 (0.78–1.07); p = 0.268. Meta-regression analysis showed lower risk of death in observational compared with randomized studies: relative risk = 0.81 (0.68–0.95); p = 0.01. Differences in age, country, hospital location, era, systolic pressure, mean arterial pressure, lactate, bundle compliance, amount of fluid administered, and hemodynamic goal achievements were not associated with survival differences between studies. Factors associated with mortality differences between early goal-directed therapy and control included Acute Physiology and Chronic Health Evaluation II (relative risk = 1.05 [1.02–1.09]; p = 0.003), Sequential Organ Failure Assessment (relative risk = 1.09 [1.00–1.18]; p = 0.04), presence of shock (relative risk = 1.007 [1.002–1.013]; p = 0.006), time-to-first antibiotic (relative risk = 1.22 [1.09–1.36]; p = 0.0006), antibiotic administration within 6 hours (relative risk = 0.20 [0.09–0.45]; p = 0.0001), 4 hours (relative risk = 0.16 [0.06–0.39]; p = 0.0001), and 3 hours (relative risk = 0.09 [0.03–0.27]; p < 0.0001). The only factors that explained mortality differences between randomized and observational studies were time-to-first antibiotic (R2 = 87%), antibiotic administration within 6 hours (R2 = 94%), 4 hours (R2 = 99%), 3 hours (R2 = 99%), and appropriate antibiotic use (R2 = 96%).
Conclusions: Survival discordance was not associated with differences in early goal-directed therapy bundle compliance or hemodynamic goal achievement. Our results suggest that it was associated with faster and more appropriate antibiotic co-intervention in the early goal-directed therapy arm compared with controls in the observational studies but not in the randomized trials. Early goal-directed therapy was associated with increased mortality in patients with high-disease severity.
Kalil, A et al
Critical Care Medicine: April 2017 - Volume 45 - Issue 4 - p 607–614
Objectives: Early goal-directed therapy has shown discordant survival outcomes in sepsis studies. We aim to find the reasons for this discordance.
Design: Random-effects and Bayesian hierarchical analyses. Setting: Studies that evaluated early goal-directed therapy. Subjects: Patients with severe sepsis and/or septic shock. Interventions: Early goal-directed therapy.
Measurements and Main Results: A total of 19,998 patients were included in the main analysis: 31 observational (n = 15,656) and six randomized (n = 4,342) studies. The analysis from 37 studies showed that early goal-directed therapy was associated with a 23% reduction in the risk of death: relative risk = 0.77 (95% CI, 0.71–0.83); p value of less than 0.0001. Mortality reduction was seen with observational studies: relative risk = 0.73 (0.67–0.80); p value of less than 0.0001 but not with randomized studies: relative risk = 0.92 (0.78–1.07); p = 0.268. Meta-regression analysis showed lower risk of death in observational compared with randomized studies: relative risk = 0.81 (0.68–0.95); p = 0.01. Differences in age, country, hospital location, era, systolic pressure, mean arterial pressure, lactate, bundle compliance, amount of fluid administered, and hemodynamic goal achievements were not associated with survival differences between studies. Factors associated with mortality differences between early goal-directed therapy and control included Acute Physiology and Chronic Health Evaluation II (relative risk = 1.05 [1.02–1.09]; p = 0.003), Sequential Organ Failure Assessment (relative risk = 1.09 [1.00–1.18]; p = 0.04), presence of shock (relative risk = 1.007 [1.002–1.013]; p = 0.006), time-to-first antibiotic (relative risk = 1.22 [1.09–1.36]; p = 0.0006), antibiotic administration within 6 hours (relative risk = 0.20 [0.09–0.45]; p = 0.0001), 4 hours (relative risk = 0.16 [0.06–0.39]; p = 0.0001), and 3 hours (relative risk = 0.09 [0.03–0.27]; p < 0.0001). The only factors that explained mortality differences between randomized and observational studies were time-to-first antibiotic (R2 = 87%), antibiotic administration within 6 hours (R2 = 94%), 4 hours (R2 = 99%), 3 hours (R2 = 99%), and appropriate antibiotic use (R2 = 96%).
Conclusions: Survival discordance was not associated with differences in early goal-directed therapy bundle compliance or hemodynamic goal achievement. Our results suggest that it was associated with faster and more appropriate antibiotic co-intervention in the early goal-directed therapy arm compared with controls in the observational studies but not in the randomized trials. Early goal-directed therapy was associated with increased mortality in patients with high-disease severity.
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