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Sarah M Perman,
Anna Marie Chang,
Judd E Hollander,
David F Gaieski,
Stephen Trzeciak,
Robert Birkhahn,
Ronny Otero,
Tiffany M Osborn,
Eugene Moretti,
H Bryant Nguyen, Kyle J Gunnerson,
David Milzman,
Munish Goyal,
Charles B Cairns,
Long Ngo,
Emanuel P Rivers,
Nathan I Shapiro
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ABSTRACT: Myocardial dysfunction is an important aspect of sepsis pathophysiology. B-type natriuretic peptide (BNP) is a neurohormone released from the ventricles in response to myocardial stretch and volume overload. The authors hypothesized that an elevated BNP in patients presenting to the emergency department (ED) with suspected sepsis are at increased risk for development of adverse events.
This was a prospective, observational, multicenter cohort study in 10 EDs. Patients were eligible if they were older than 18 years, had two or more systemic inflammatory response syndrome (SIRS) criteria, and had suspected infection or a serum lactate level > 2.5 mmol/L. Patients were excluded if they were pregnant, had do-not-attempt-resuscitation status, sustained a cardiac arrest prior to hospital arrival, had known chronic renal insufficiency, or were on dialysis. BNP levels were obtained at arrival. The primary outcome was a composite of severe sepsis, septic shock within 72 hours, or in-hospital mortality.
There were 825 patients enrolled (mean ± standard deviation [SD] age = 53.5 ± 19.6 years; 51% were female and 37% were African American). The area under the curve (AUC) for BNP to predict the triple composite outcome was 0.69, and the optimal cut-point of BNP was 49 pg/mL. Patients with a BNP > 49 pg/mL had a greater mortality rate (11.6% vs. 2.1%; p = 0.0001), a greater risk of development of severe sepsis (67.7% vs. 36.8%; p = 0.0001) and septic shock (51.7% vs. 26.4%; p = 0.0001), and a higher rate of the triple composite outcome (69% vs. 37%; unadjusted odds ratio [OR] = 1.9, 95% confidence interval [CI] = 1.6 to 2.1; p < 0.001). The sensitivity was 63% (95% CI = 58% to 67%), specificity was 69% (95% CI = 65% to 73%), negative predictive value (NPV) was 63% (95% CI = 58% to 67%), and positive predictive value (PPV) was 69% (95% CI = 65% to 74%). In multivariate modeling, after adjusting for age, sex, heart rate, white blood cell count, and creatinine, an elevated BNP was associated with increased odds of having the composite outcome. The outcome was similar in the subset of patients who did not have severe sepsis or septic shock upon arrival.
In patients who present to the ED with SIRS criteria and suspected infection, an elevated BNP is associated with a worse prognosis but has limited diagnostic utility.
Academic Emergency Medicine 02/2011; 18(2):219-22. · 1.86 Impact Factor
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Journal of critical care 02/2011; 26(1):97-8. · 2.13 Impact Factor
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ABSTRACT: Critical care medicine (CCM) is of growing interest among emergency physicians (EPs), but the number of CCM-trained EPs and their postfellowship practice is unknown. This study's purpose was to conduct a descriptive census survey of EPs who have completed or are currently in a CCM fellowship.
The authors created a Web-based survey, and requests to participate were sent to EPs who have completed or are currently in a CCM fellowship. Responses were collected over a 12-month period. Physicians were located via multiple whom electronic mailing lists, including the Emergency Medicine Section of the Society of Critical Care Medicine, Critical Care Section of the American College of Emergency Physicians, and the Emergency Medicine Residents' Association. The authors also contacted CCM fellowship coordinators and used informal networking. Data were collected on emergency medicine (EM) and other residency training; discipline, duration, and year of CCM fellowship; current practice setting; and board certification status, including the European Diploma in Intensive Care (EDIC).
A total of 104 physicians completed the survey (97% response rate), of whom 73 had completed fellowship at the time of participation, and 31 of whom were in fellowship training. Of those who completed fellowship, 36/73 (49%) practice both EM and CCM, and 45/73 (62%) practice in academic institutions. Multiple disciplines of fellowship were represented: multidisciplinary (39), surgical (28), internal medicine (16), anesthesia (14), and other (4). Together, the CCM fellowships at the University of Maryland R Adams Cowley Shock Trauma Center and the University of Pittsburgh have trained 42% of all EM-CCM physicians, with 38 other institutions training from one to four fellows each. The number of EPs completing CCM fellowships has risen: from 1974 to 1989, 12 EPs; from 1990 to 1999, 15 EPs; and from 2000 to 2007, 43 EPs.
Emergency physicians are entering CCM fellowships in increasing numbers. Almost half of these EPs practice both EM and CCM.
Academic Emergency Medicine 03/2010; 17(3):325-9. · 1.86 Impact Factor
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ABSTRACT: Abnormalities of strong ion gap (SIG) are common in critically ill intensive care unit (ICU) patients in conjunction with a high incidence of acid-base abnormalities. However, it is unknown whether abnormalities in SIG are also seen in ICU patients without active acid-base abnormalities. Thus, we conducted this pilot study to examine differences in quantitative acid-base variables between healthy adult volunteers and stable ICU patients with no suspected acid-base abnormalities.
The study used a prospective observational study of 2 cohorts, 15 healthy adult volunteers and 15 stable adult patients just before ICU discharge who were not receiving renal replacement therapy and had no known active acid-base derangements. We analyzed venous blood for acid-base variables (potential hydrogen in central venous blood [pH(CV)], partial tension of carbon dioxide in central venous blood [p(CV)co(2)], standard base excess [SBE], lactate, Na(+), K(+), Cl(-), Mg(2+), Ca(2+), phosphate, and albumin). From these, we calculated strong ion difference (SID) and SIG for both cohorts.
Although mean values for pH(CV), p(CV)CO(2), and SBE were within the normal range in both cohorts, 10 (66.7%) of 15 of ICU patients were found to have occult acid-base disorders. The ICU patients also had reduced albumin and SID measurements and significantly greater mean SIG (5.1 ± 2.9 mEq/L) compared to healthy controls (1.4 ± 1.8 mEq/L) (P = .0002). None of the healthy controls had a SIG higher than 5.0 mEq/L, whereas 7 (46.7%) of 15 of ICU patients had a SIG higher than 5.0 mEq/L. Even among ICU patients with no abnormalities of pH(CV), p(CV)CO(2), and SBE, mean SIG was 6.4 (± 3.3 mEq/L).
Stable ICU patients have much higher levels of unexplained anions when comparing with healthy controls. Whether this finding represents occult acid-base disorders or simply metabolic differences among the critically ill is uncertain. Further study in larger populations is warranted to establish the significance of high SIG in otherwise stable ICU patients.
Journal of critical care 11/2009; 25(3):520-4. · 2.13 Impact Factor
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Nathan I. Shapiro,
Stephen Trzeciak,
Judd E. Hollander,
Robert Birkhahn,
Ronny Otero,
Tiffany M. Osborn,
Eugene Moretti,
H Bryant Nguyen, Kyle J. Gunnerson,
David Milzman,
David F. Gaieski,
Munish Goyal,
Charles B. Cairns,
Long Ngo,
Emanuel P. Rivers
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ABSTRACT: Objective: To define a biomarker panel to predict organ dysfunction, shock, and in-hospital mortality in emergency department (ED) patients with suspected sepsis.
Design: Prospective observational study.
Setting: EDs of ten academic medical centers.
Patients: There were 971 patients enrolled. Inclusion criteria: 1) ED patients age > 18; 2) suspected infection or a serum lactate level > 2.5 mmol/L; and 3) two or more systemic inflammatory response syndrome criteria. Exclusion criteria: pregnancy, do-not-resuscitate status, or cardiac arrest.
Measurements and Main Results: Nine biomarkers were assayed from blood draws obtained on ED presentation. Multivariable logistic regression was used to identify an optimal combination of biomarkers to create a panel. The derived formula for weighting biomarker values was used to calculate a “sepsis score,” which was the predicted probability of the primary outcome of severe sepsis (sepsis plus organ dysfunction) within 72 hrs. We also assessed the ability of the sepsis score to predict secondary outcome measures of septic shock within 72 hrs and in-hospital mortality. The overall rates of each outcome were severe sepsis, 52%; septic shock, 39%; and in-hospital mortality 7%. Among the nine biomarkers tested, the optimal 3-marker panel was neutrophil gelatinase-associated lipocalin, protein C, and interleukin−1 receptor antagonist. The area under the curve for the accuracy of the sepsis score derived from these three biomarkers was 0.80 for severe sepsis, 0.77 for septic shock, and 0.79 for death. When included in multivariate models with clinical variables, the sepsis score remained highly significant (p < 0.001) for all the three outcomes.
Conclusions: A biomarker panel of neutrophil gelatinase-associated lipocalin, interleukin-1ra, and Protein C was predictive of severe sepsis, septic shock, and death in ED patients with suspected sepsis. Further study is warranted to prospectively validate the clinical utility of these biomarkers and the sepsis score in risk-stratifying patients with suspected sepsis.
Critical Care Medicine 12/2008; 37(1):96-104. · 6.33 Impact Factor
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ABSTRACT: To determine if animals with abnormally low albumin levels are more susceptible to the effects of hypercapnia on BP compared to normal animals.
Prospective, controlled laboratory experiment.
University research laboratory. Animals: Eighteen male Sprague-Dawley rats: 6 rats 10 to 12 weeks old (young Sprague-Dawley [YSD]), 6 rats 6 to 9 months old (old Sprague-Dawley [OSD]), and 6 rats 10 to 12 weeks old (Nagase analbuminemic mutant Sprague-Dawley [NAR]).
Under general anesthesia and paralysis, we varied the Paco(2) by changing the respiratory rate on mechanical ventilation. Mean arterial pressure (MAP) was monitored in a continuous fashion. We obtained arterial blood for blood gas and electrolyte analysis, and nitric oxide (NO) production.
OSD rats had reduced serum albumin, while NAR rats were analbuminemic. Although NAR animals had a decreased buffer capacity compared to age-matched control animals (0.010 vs 0.013, p < 0.05), the MAP decreased in an identical fashion in all three groups. NO production increased with hypercapnia but was similar in all three groups. However, NAR rats had consistently higher plasma strong ion gap (2.8 to 4.1 mEq/L greater) compared to either YSD or OSD rats (p < 0.01), and baseline strong ion difference (mean +/- SD) was significantly lower in NAR rats (28.7 +/- 2.1 mEq/L) compared to either YSD rats (33.0 +/- 5.1 mEq/L) or OSD rats (31.2 +/- 5.1 mEq/L) [p < 0.05].
These findings suggest that analbuminemic or hypoalbuminemic rats are not more susceptible to hypercapnia-induced hemodynamic instability. Baseline values for apparent strong ion difference are lower in NA rats consistent with a reduced buffer base resulting from analbuminemia.
Chest 05/2007; 131(5):1295-300. · 5.25 Impact Factor
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Ronny M Otero,
H Bryant Nguyen,
David T Huang,
David F Gaieski,
Munish Goyal, Kyle J Gunnerson,
Stephen Trzeciak,
Robert Sherwin,
Christopher V Holthaus,
Tiffany Osborn,
Emanuel P Rivers
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ABSTRACT: Studies of acute myocardial infarction, trauma, and stroke have been translated into improved outcomes by earlier diagnosis and application of therapy at the most proximal stage of hospital presentation. Most therapies for these diseases are instituted prior to admission to an ICU; this approach to the sepsis patient has been lacking. In response, a trial comparing early goal-directed therapy (EGDT) vs standard care was performed using specific criteria for the early identification of high-risk sepsis patients, verified definitions, and a consensus-derived protocol to reverse the hemodynamic perturbations of hypovolemia, vasoregulation, myocardial suppression, and increased metabolic demands. Five years after the EGDT publication, there has been much discussion generated with regard to the concepts of EGDT, as well as debate fueled regarding diagnostic and therapeutic interventions. However, during this time period further investigations by the primary investigators and others have brought additional contemporary findings. EGDT modulates some of the components of inflammation, as reflected by improved organ function. The end points used in the EGDT protocol, the outcome results, and the cost-effectiveness have subsequently been externally validated, revealing similar or even better findings than those from the original trial. Although EGDT is faced with challenges, a coordinated approach to sepsis management is necessary to duplicate the progress in outcomes seen in patients with conditions such as acute myocardial infarction, stroke, and trauma.
Chest 12/2006; 130(5):1579-95. · 5.25 Impact Factor
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ABSTRACT: Acid-base abnormalities are common in the intensive care unit (ICU). Differences in outcome exist between respiratory and metabolic acidosis in similar pH ranges. Some forms of metabolic acidosis (for example, lactate) seem to have worse outcomes than others (for example, chloride). The relative incidence of each type of disorder is unknown. We therefore designed this study to determine the nature and clinical significance of metabolic acidosis in critically ill patients.
An observational, cohort study of critically ill patients was performed in a tertiary care hospital. Critically ill patients were selected on the clinical suspicion of the presence of lactic acidosis. The inpatient mortality of the entire group was 14%, with a length of stay in hospital of 12 days and a length of stay in the ICU of 5.8 days.
We reviewed records of 9,799 patients admitted to the ICUs at our institution between 1 January 2001 and 30 June 2002. We selected a cohort in which clinicians caring for patients ordered a measurement of arterial lactate level. We excluded patients in which any necessary variable required to characterize an acid-base disorder was absent. A total of 851 patients (9% of ICU admissions) met our criteria. Of these, 548 patients (64%) had a metabolic acidosis (standard base excess < -2 mEq/l) and these patients had a 45% mortality, compared with 25% for those with no metabolic acidosis (p < 0.001). We then subclassified metabolic acidosis cases on the basis of the predominant anion present (lactate, chloride, or all other anions). The mortality rate was highest for lactic acidosis (56%); for strong ion gap (SIG) acidosis it was 39% and for hyperchloremic acidosis 29% (p < 0.001). A stepwise logistic regression model identified serum lactate, SIG, phosphate, and age as independent predictors of mortality.
In critically ill patients in which a measurement of lactate level was ordered, lactate and SIG were strong independent predictors of mortality when they were the major source of metabolic acidosis. Overall, patients with metabolic acidosis were nearly twice as likely to die as patients without metabolic acidosis.
Critical care (London, England) 03/2006; 10(1):R22. · 4.61 Impact Factor
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Kyle J Gunnerson
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ABSTRACT: Acid-base abnormalities are common in critically ill patients. Our ability to describe acid-base disorders must be precise. Small differences in corrections for anion gap, different types of analytical processes, and the basic approach used to diagnose acid-base aberrations can lead to markedly different interpretations and treatment strategies for the same disorder. By applying a quantitive acid-base approach, clinicians are able to account for small changes in ion distribution that may have gone unrecognized with traditional techniques of acid-base analysis. Outcome prediction based on the quantitative approach remains controversial. This is in part due to use of various technologies to measure acid-base variables, administration of fluid or medication that can alter acid-base results, and lack of standardized nomenclature. Without controlling for these factors it is difficult to appreciate the full effect that acid-base disorders have on patient outcomes, ultimately making results of outcome studies hard to compare.
Critical care (London, England) 11/2005; 9(5):508-16. · 4.61 Impact Factor
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ABSTRACT: Demand for critical care services is increasing. Unless the supply of intensivists increases, critically ill patients will not have access to intensivists. Recent critical care society recommendations include increased graduate medical education support and expansion of the J-1 visa waiver program for foreign medical graduates. This article proposes additional recommendations, based on strengthening the relationship between emergency medicine and critical care medicine. Demand for critical care services is increasing. Unless the supply of intensivists increases, critically ill patients will not have access to intensivists. Recent critical care society recommendations include increased graduate medical education support and expansion of the J-1 visa waiver program for foreign medical graduates. This article proposes additional recommendations, based on strengthening the relationship between emergency medicine (EM) and critical care medicine (CCM). Critical care is a continuum that includes prehospital, emergency department (ED), and intensive care unit (ICU) care teams. Both EM and CCM require expertise in treating life-threatening acute illness, with many critically ill patients often presenting first to the ED. Increased patient volumes and acuity have resulted in longer ED lengths of stay and more critical care delivery in the ED. However, the majority of CCM fellowships do not accept EM residents, and those who successfully complete a fellowship do not have access to a U.S. certification exam in CCM. Despite these barriers, interest in CCM training among EM physicians is increasing. Dual EM/CCM-trained physicians not only will help alleviate the intensivist shortage but also will strengthen critical care delivery in the ED and facilitate coordination at the ED-ICU interface. We therefore propose that all accreditation bodies work cooperatively to create a route to CCM certification for emergency physicians who complete a critical care fellowship.
Critical Care Medicine 10/2005; 33(9):2104-9. · 6.33 Impact Factor
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ABSTRACT: Disorders of acid-base and electrolytes are commonly seen in critically ill patients. The presence of these disorders typically signals the development of an underlying pathology. These disturbances can be severe and are often associated with worse outcome. Indeed, metabolic acidosis is one of the ways we quantify organ failure. Although acid-base and electrolyte disorders may be a result of the underlying pathophysiology (eg, renal failure, respiratory failure, shock), they may also result from the way in which we manage critically ill patients.
The application of the physical-chemical approach to acid-base analysis has led to recent developments in the identification and quantification and understanding of mechanisms for acid-base disorders commonly found in critically ill patients. Examples include a better understanding of the role of electrolytes (especially sodium and chloride) and weak acids in the pathophysiology of acid-base disorders, the implication of acid-base derangements on the inflammatory process and organ perfusion, and the importance of resuscitation fluid composition.
By adopting a physical-chemical approach to acid-base analysis we are gaining insight to the complexities of acid-base disorders and how their treatments may affect outcome.
Current Opinion in Critical Care 01/2004; 9(6):468-73. · 2.51 Impact Factor
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Annals of Emergency Medicine 07/2003; 41(6):886-7; author reply 887. · 4.13 Impact Factor
