Part 2 book Year book - Year book of critical care medicine 2013 presents the following contents: Sepsis/septic shock, metabolism/gastrointestinal/nutrition/hematology-oncology, neurologic - Traumatic and non traumatic, renal, trauma and overdose, ethics/socioeconomic/administrative/issues, pharmacology/sedation analgesia.
6 Sepsis/Septic Shock Prognostic Value of Incremental Lactate Elevations in Emergency Department Patients With Suspected Infection Puskarich MA, Kline JA, Summers RL, et al (Univ of Mississippi Med Ctr, Jackson; Carolinas Med Ctr, Charlotte, NC) Acad Emerg Med 19:983-985, 2012 Objectives.dPrevious studies have confirmed the prognostic significance of lactate concentrations categorized into groups (low, intermediate, high) among emergency department (ED) patients with suspected infection Although the relationship between lactate concentrations categorized into groups and mortality appears to be linear, the relationship between lactate as a continuous measurement and mortality is uncertain This study sought to evaluate the association between blood lactate concentrations along an incremental continuum up to a maximum value of 20 mmol/L and mortality Methods.dThis was a retrospective cohort analysis of adult ED patients with suspected infection from a large urban ED during 2007e2010 Inclusion criteria were suspected infection evidenced by administration of antibiotics in the ED and measurement of whole blood lactate in the ED The primary outcome was in-hospital mortality Logistic and polynomial regression were used to model the relationship between lactate concentration and mortality Results.dA total of 2,596 patients met inclusion criteria and were analyzed The initial median lactate concentration was 2.1 mmol/L (interquartile range [IQR] ¼ 1.3 to 3.3 mmol/L) and the overall mortality rate was 14.4% In the cohort, 459 patients (17.6%) had initial lactate levels > mmol/L Mortality continued to rise across the continuum of incremental elevations, from 6% for lactate < 1.0 mmol/L up to 39% for lactate 19e20 mmol/L Polynomial regression analysis showed a strong curvilinear correlation between lactate and mortality (R ¼ 0.72, p < 0.0001) Conclusions.dIn ED patients with suspected infection, we found a curvilinear relationship between incremental elevations in lactate concentration and mortality These data support the use of lactate as a continuous variable rather than a categorical variable for prognostic purposes : Previous studies have shown that increased serum lactate correlates with increased mortality However, these studies all used categorical lactates (eg, normal, low, intermediate, high) This study questioned whether lactate as a continuous variable (it is after all) correlated with mortality in patients with 135 136 / Critical Care Medicine suspected infection Patients admitted to the hospital from the emergency department were included if they had suspected infection (antibiotics given in the emergency department) and a lactate measurement obtained More than 2500 patients were enrolled and they seemed to represent a typical sepsis cohort based on length of stay, comorbidities, and mortality The authors found definite correlations between incremental increases of lactate and incremental increases in mortality They developed a regression model/equation that fit their data quite well In other words, with a given lactate, their equation could predict mortality This study was well done by a group of researchers with a good track record Pay attention to lactate in patients with suspected infection: the higher it is, the more likely the patient in front of you is going to die M D Zwank, MD Can changes in arterial pressure be used to detect changes in cardiac index during fluid challenge in patients with septic shock? Pierrakos C, Velissaris D, Scolletta S, et al (Erasme Univ Hosp, Brussels, Belgium) Intensive Care Med 38:422-428, 2012 Purpose.dResponse to fluid challenge is often defined as an increase in cardiac index (CI) of more than 10e15% However, in clinical practice CI values are often not available We evaluated whether changes in mean arterial pressure (MAP) correlate with changes in CI after fluid challenge in patients with septic shock Methods.dThis was an observational study in which we reviewed prospectively collected data from 51 septic shock patients in whom complete hemodynamic measurements had been obtained before and after a fluid challenge with 1,000 ml crystalloid (Hartman’s solution) or 500 ml colloid (hydroxyethyl starch 6%) CI was measured using thermodilution Patients were divided into two groups (responders and nonresponders) according to their change in CI (responders: %CI > 10%) after the fluid challenge Statistical analysis was performed using a twoway analysis of variance test followed by a Student’s t test with adjustment for multiple comparisons Pearson’s correlation and receiver operating characteristic curve analysis were also used Results.dMean patient age was 67 ± 17 years and mean Sequential Organ Failure Assessment (SOFA) upon admittance to the intensive care unit was 10 ± In the 25 responders, MAP increased from 69 ± to 77 ± mmHg, pulse pressure (PP) increased from 59 ± 15 to 67 ± 16, and CI increased from 2.8 ± 0.8 to 3.4 ± 0.9 L/min/m2 (all p < 0.001) There were no significant correlations between the changes in MAP, PP, and CI Conclusions.dChanges in MAP not reliably track changes in CI after fluid challenge in patients with septic shock and, consequently, Chapter 6eSepsis/Septic Shock / 137 should be interpreted carefully when evaluating the response to fluid challenge in such patients : Accurate, dynamic markers of fluid responsiveness in shock are highly sought after but often remain illusive In a prospective observational study, Pierrakos et al assessed whether changes in arterial pressure could predict fluid responsiveness of 51 septic shock patients by determining the percentage of change in cardiac index (CI) via the thermodilution method Half of the patients were determined to be fluid responders as defined by a greater than 10% increase in CI after fluid challenge with L crystalloid or 500 mL colloid bolus While pulse pressure and mean arterial pressure (MAP) significantly increased in responders when challenged with a fluid bolus, there was no significant correlation with CI The lack of correlation between changes in arterial pressure and cardiac index should caution the intensivist that an increase in MAP after volume expansion does not necessarily improve hemodynamic status In other words, augmentation of MAP with a fluid challenge does not accurately identify fluid responsiveness in septic shock patients E Damuth, MD Multiplex polymerase chain reaction pathogen detection in patients with suspected septicemia after trauma, emergency, and burn surgery Tran NK, Wisner DH, Albertson TE, et al (Univ of California, Davis) Surgery 151:456-463, 2012 Background.dThe goal of this study is to determine the clinical value of multiplex polymerase chain reaction (PCR) study for enhancing pathogen detection in patients with suspected septicemia after trauma, emergency, and burn surgery PCR-based pathogen detection quickly reveals occult bloodstream infections in these high-risk patients and may accelerate the initiation of targeted antimicrobial therapy Methods.dWe conducted a prospective observational study comparing results for 30 trauma and emergency surgery patients to 20 burn patients Whole-blood samples collected with routine blood cultures (BCs) were tested using a new multiplex, PCR-based, pathogen detection system PCR results were compared to culture data Results.dPCR detected rapidly more pathogens than culture methods Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), and Multiple Organ Dysfunction (MODS) scores were greater in PCR-positive versus PCR-negative trauma and emergency surgery patients (P #.033) Negative PCR results (odds ratio, 0.194; 95% confidence interval, 0.045e0.840; P ¼.028) acted as an independent predictor of survival for the combined surgical patient population Conclusion.dPCR detected the presence of pathogens more frequently than blood culture These PCR results were reported faster than blood culture results Severity scores were significantly greater in PCR-positive 138 / Critical Care Medicine trauma and emergency surgery patients The lack of pathogen DNA as determined by PCR served as a significant predictor of survival in the combined patient population PCR testing independent of traditional prompts for culturing may have clinical value in burn patients These results warrant further investigation through interventional trials : Trauma, emergency, and burn surgery patients are at a particularly high risk of septicemia secondary to their disease states As a result, immediate empiric antibiotic treatment is necessary to improve mortality.1 However, with increasing resistant pathogens, aggressive de-escalation is important as well In this prospective, observational study, patients displaying signs and symptoms of sepsis had blood cultures and blood samples run through polymerase chain reaction (PCR) Arbitrated case reviews were performed to determine if appropriate antibiotic regimens were dispensed, given first blood culture results alone and then PCR results PCR had a markedly increased turnaround time (5.9 h vs 25.3 h) Additionally, PCR was positive in 11 cases, whereas blood cultures were either negative or failed to identify pathogen species Arbitrated case review found antimicrobial therapy was inadequate relative to PCR results in 29% PCR-positive patients PCR was found to have more pathogen detection events, even in serial samples while patients were on concurrent antimicrobial therapy A negative PCR was found to be an independent predictor of survival While this practice is cost prohibitive and not approved by the US Food and Drug Administration, PCR can be a very powerful tool in early pathogen detection in sepsis It can also serve as a predictor for mortality According to the authors, it does have its limitations: it is dependent on the assay to detect specific pathogens, genetic polymorphisms, and whole blood sample matrix effects C Cho, MD S Zanotti, MD Reference MacArthur RD, Miller M, Albertson T, et al Adequacy of early empiric antibiotic treatment and survival in severe sepsis: experience from the MONARCS trial Clin Infect Dis 2004;38:284-288 Advances in Mesenchymal Stem Cell Research in Sepsis Wannemuehler TJ, Manukyan MC, Brewster BD, et al (Indiana Univ School of Medicine, Indianapolis) J Surg Res 173:113-126, 2012 Background.dSepsis remains a source of morbidity and mortality in the postoperative patient despite appropriate resuscitative and antimicrobial approaches Recent research has focused upon additional interventions such as exogenous cell-based therapy Mesenchymal stem cells (MSCs) exhibit multiple beneficial properties through their capacity for homing, attenuating the inflammatory response, modulating immune cells, and Chapter 6eSepsis/Septic Shock / 139 promoting tissue healing Recent animal trials have provided evidence that MSCs may be useful therapeutic adjuncts Materials and Methods.dA directed search of recent medical literature was performed utilizing PubMed to examine the pathophysiology of sepsis, mechanisms of mesenchymal stem cell interaction with host cells, sepsis animal models, and recent trials utilizing stem cells in sepsis Results.dMSCs continue to show promise in the treatment of sepsis by their intrinsic ability to home to injured tissue, secrete paracrine signals to limit systemic and local inflammation, decrease apoptosis in threatened tissues, stimulate neoangiogenesis, activate resident stem cells, beneficially modulate immune cells, and exhibit direct antimicrobial activity These effects are associated with reduced organ dysfunction and improved survival in animal models Conclusion.dResearch utilizing animal models of sepsis has provided a greater understanding of the beneficial properties of MSCs Their capacity to home to sites of injury and use paracrine mechanisms to change the local environment to ultimately improve organ function and survival make MSCs attractive in the treatment of sepsis Future studies are needed to further evaluate the complex interactions between MSCs and host tissues : Sepsis holds a mortality rate of 28.6% and costs $16.7 billion nationally As such, immediate, effective treatment for a septic patient is vital Interest in mesenchymal stem cells (derived from bone marrow, adipose, placenta, and umbilical cord) has been applied in the treatment of sepsis for its multiple abilities, which is reviewed in this article Mesenchymal stem cells have the ability to home to injured tissues, partly from interacting with host cytokines They also have paracrine signaling effects to promote tissue regeneration, prevent tissue loss, and improve tissue function via its anti-inflammatory, antiapoptotic, nonangiogenic activation of resident stem cell and immunomodulatory capabilities Although in vivo studies mesenchymal cells also had antimicrobial effects, vitro models revealed they could not Thus, they likely require host cell stimulation and signaling to so In animal studies, stem cell treatment of sepsis has shown reduced levels of proinflammatory cytokines (interleukin-1, tumor necrosis factor-a, interleukin-6), decreased organ injury, and increased organ function Additionally, stem cells can improve bacterial clearance through increased macrophage phagocytic activity More importantly, septic animals treated with stem cells had a significantly improved survival rate In conclusion, mesenchymal stem cells administration is a promising treatment for sepsis through its multiple effects on the host’s immune system, organ tissue, and function Although there are no clinical trials as of yet, continued research in the animal model is crucial S Zanotti, MD 140 / Critical Care Medicine A multicenter trial to compare blood culture with polymerase chain reaction in severe human sepsis Bloos F, Hinder F, Becker K, et al (Univ Hosp Jena, Germany; Univ Hosp Muănster, Germany) Intensive Care Med 36:241-247, 2010 Objective.dTo assess the presence of microbial DNA in the blood by polymerase chain reaction (PCR) and its association with disease severity and markers of inflammation in severe sepsis and to compare the performance of PCR with blood culture (BC) Design.dProspective multicentric controlled observational study Setting.dThree surgical intensive care units in university centers and large teaching hospitals Patients.dOne hundred forty-two patients with severe sepsis and 63 surgical controls Interventions.dPresence of microbial DNA was assessed by multiplex PCR upon enrollment, and each time a BC was obtained Measurements and Main Results.dControls had both approximately 4% positive PCRs and BCs In severe sepsis, 34.7% of PCRs were positive compared to 16.5% of BCs (P < 0.001) Consistently, 70.3% of BCs had a corresponding PCR result, while only 21.4% of PCR results were confirmed by BC Compared to patients with negative PCRs at enrollment, those testing positive had higher organ dysfunction scores [SOFA, median (25the75th percentile) 12 (7e15) vs (7e11); P ¼ 0.023] and a trend toward higher mortality (PCR negative 25.3%; PCR positive 39.1%; P ¼ 0.115) Conclusions.dIn septic patients, concordance between BC and PCR is moderate However, PCR-based pathogen detection correlated with disease severity even if the BC remained negative, suggesting that presence of microbial DNA in the bloodstream is a significant event The clinical utility to facilitate treatment decisions warrants investigation : Sepsis is one of the most important causes of morbidity and mortality in critically ill patients The administration of early appropriate antibiotics is a cornerstone of sepsis therapy Studies have shown that mortality is increased with delays in initiating antibiotics that cover the culprit pathogen in sepsis This has led to an increase in the use of initial empiric antibiotic regimens with broad coverage Without proper de-escalation, the increased use of broad-spectrum antibiotics will lead to increased antibiotic resistance Unfortunately, negative blood cultures are a common occurrence in sepsis This makes modification of antibiotic regimes and diagnosis of infection difficult Many experts have proposed that culture-independent molecular biologye based diagnostic tests, such as real-time polymerase chain reaction (PCR), could overcome some of the limitations cultures present and be more useful in the management of sepsis In this intriguing prospective multicenter study, the authors assessed the diagnostic utility of culture-independent PCR-based detection of pathogens compared with blood cultures (BC) in sepsis The study Chapter 6eSepsis/Septic Shock / 141 basically found that concordance between BC and PCR was moderate in septic patients There were more positive PCRs with negative BCs However, negative PCRs were still common, making it unlikely that at present a negative PCR could be used to rule out infection and/or stop antibiotics An additional finding of great interest was the correlation of a positive PCR (presence of microbial DNA in the bloodstream) with increased severity and poor outcomes This finding suggests that the presence of bacteria DNA (even with negative blood cultures) is an important clinical finding and may warrant further investigation regarding its value to guide therapeutic interventions S Zanotti, MD Diagnostic value of positron emission tomography combined with computed tomography for evaluating patients with septic shock of unknown origin Kluge S, Braune S, Nierhaus A, et al (Univ Med Ctr Hamburg-Eppendorf, Germany) J Crit Care 27:316.e1-316.e7, 2012 Purpose.d18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) combined with computed tomography (CT) is a promising new tool for the identification of infectious foci The aim of our work was to evaluate the diagnostic value of FDG-PET/CT in critically ill patients with septic shock of unknown origin Methods.dWe performed a single-center, 6-year retrospective evaluation of the value of FDG-PET/CT in critically ill patients with severe sepsis or septic shock of unknown origin Results.dEighteen patients underwent FDG-PET/CT Microbiological tests (blood culture, urine, and respiratory secretions), chest x-rays, CT scans, and transesophageal echocardiography were performed on all patients before FDG-PET/CT scanning Pathologic FDG accumulation could be demonstrated in 14 of 18 FDG-PET/CT scans On a per-patient basis, 11 were “true positive,” were “false positive,” were true negative, and there were no false negatives In cases, the results of the PET/CT scan had direct therapeutic consequences (surgery, 2; pacemaker removal, 2; initiation of antibiotic therapy, 1; and prolonged antibiotic therapy, 1); 12 (66%) of the 18 patients survived to hospital discharge Conclusions.dThe FDG-PET/CT is a valuable tool for the localization of infectious foci in critically ill patients with severe sepsis/septic shock in whom conventional diagnostic methods fail to detect these foci Prospective studies with more patients are warranted to further evaluate the diagnostic accuracy and feasibility of this diagnostic tool in critically ill patients with severe sepsis : Positron emission tomography/computed tomography (PET/CT) is well established in the arena of oncologic imaging and evaluation of chronic infections Its potential role in evaluating acute infections and patients with severe 142 / Critical Care Medicine sepsis and septic shock is undetermined Simons et al (2010) previously investigated the role of PET/CT in mechanically ventilated intensive care unit (ICU) patients.1 This study presents a novel application of an established modality to evaluate for acute infections in the setting of severe sepsis and septic shock This was a retrospective observational study in all adult ICU patients over a 6-year period with severe sepsis or septic shock with an unknown source who underwent PET/CT evaluation The results of PET/CT were compared with a final diagnosis that was made using all clinical information excluding the PET/CT findings In cases (27%), PET/CT was essential for diagnosis in the following cases: pseudomembranous colitis, infected bypass graft, infected inferior vena cava thrombus, infected pacemaker, and cervical abscess In cases (33%), PET/CT results altered patient management The survival rate for this group of patients was 66% Most of the patients in this study were evaluated for persistent fever or suspected septic emboli This study did not specify severe sepsis or septic shock as indications In 14% of patients, the PET/CT results altered management The limitations of the current study were the retrospective design and the small study population A major drawback of PET/CT in the critical care setting is the time required for the exam, the expense, and availability as an inpatient PET/CT evaluation may serve as an important adjunct for diagnosis of sources of severe sepsis or septic shock when other modalities (clinical, microbiologic, and anatomic imaging) have proven unrevealing Further validation of this modality in sepsis in a prospective randomized trial would determine if a survival benefit exists A F Miller, MD S Zanotti, MD Reference Simons KS, Pickkers P, Bleeker-Rovers CP, Oyen WJ, van der Hoeven JG F-18fluorodeoxyglucose positron emission tomography combined with CT in critically ill patients with suspected infection Intensive Care Med 2010;36:504-511 Early goal-directed therapy (EGDT) for severe sepsis/septic shock: which components of treatment are more difficult to implement in a community-based emergency department? O’Neill R, Morales J, Jule M (Genesys Regional Med Ctr, Grand Blanc, MI) J Emerg Med 42:503-510, 2012 Background.dEarly goal-directed therapy (EGDT) has been shown to reduce mortality in patients with severe sepsis/septic shock, however, implementation of this protocol in the emergency department (ED) is sometimes difficult Objectives.dWe evaluated our sepsis protocol to determine which EGDT elements were more difficult to implement in our communitybased ED Chapter 6eSepsis/Septic Shock / 143 Methods.dThis was a non-concurrent cohort study of adult patients entered into a sepsis protocol at a single community hospital from July 2008 to March 2009 Charts were reviewed for the following process measures: a predefined crystalloid bolus, antibiotic administration, central venous catheter insertion, central venous pressure measurement, arterial line insertion, vasopressor utilization, central venous oxygen saturation measurement, and use of a standardized order set We also compared the individual component adherence with survival to hospital discharge Results.dA total of 98 patients presented over a 9-month period Measures with the highest adherence were vasopressor administration (79%; 95% confidence interval [CI] 69e89%) and antibiotic use (78%; 95% CI 68e85%) Measures with the lowest adherence included arterial line placement (42%; 95% CI 32e52%), central venous pressure measurement (27%; 95% CI 18e36%), and central venous oxygen saturation measurement (15%; 95% CI 7e23%) Fifty-seven patients survived to hospital discharge (Mortality: 33%) The only element of EDGT to demonstrate a statistical significance in patients surviving to hospital discharge was the crystalloid bolus (79% vs 46%) (respiratory rate [RR] ¼ 1.76, 95% CI 1.11e2.58) Conclusion.dIn our community hospital, arterial line placement, central venous pressure measurement, and central venous oxygen saturation measurement were the most difficult elements of EGDT to implement Patients who survived to hospital discharge were more likely to receive the crystalloid bolus : It has been more than a decade since the publication of the landmark early goal-directed therapy (EGDT) study by Rivers et al.1 This study showed a significant improvement in mortality in patients with severe sepsis-induced hypoperfusion treated with EGDT Despite the questions that remain unanswered and concerns with specific aspects of the trial, EGDT has been widely recommended by various guidelines, such as the Surviving Sepsis Guidelines.2 In this study, the investigators sought to evaluate the adherence of specific elements of the EGDT protocol in a community emergency department (ED) The authors report that arterial line placement, central venous pressure measurement, and central venous oxygen saturation measurement were the most difficult elements of EGDT to implement The authors also report that the patients who survived to hospital discharge were more likely to receive the crystalloid bolus (2 L in the first hour) as prescribed in their protocol Although this study does not provide answers to which aspects of EGDT work in decreasing survival, it does shed important light on some of the barriers that still persist in the implementation of these protocols in community EDs Currently, there are large multicenter studies evaluating different aspects of EGDT and resuscitation of patients with severe sepsis/septic shock The results of these ongoing trials may help define the best way forward S Zanotti, MD 144 / Critical Care Medicine References Rivers E, Nguyen B, Havstad S, et al Early goal-directed therapy in the treatment of severe sepsis and septic shock N Engl J Med 2001;345:1368-1377 Dellinger RP, Levy MM, Carlet JM, et al Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008 Crit Care Med 2008;36:296-327 Antibiotic strategies in severe nosocomial sepsis: Why we not deescalate more often? Heenen S, Jacobs F, Vincent J-L (Erasme Hosp, Brussels, Belgium) Crit Care Med 40:1404-1409, 2012 Objectives.dTo assess the use of antibiotic de-escalation in patients with hospital-acquired severe sepsis in an academic setting Design.dWe reviewed all episodes of severe sepsis treated over a 1-yr period in the department of intensive care Antimicrobial therapy was considered as appropriate when the antimicrobial had in vitro activity against the causative microorganisms According to the therapeutic strategy in the days after the start of antimicrobial therapy, we classified patients into four groups: de-escalation (interruption of an antimicrobial agent or change of antibiotic to one with a narrower spectrum); no change in antibiotherapy; escalation (addition of a new antimicrobial agent or change in antibiotic to one with a broader spectrum); and mixed changes Setting.dA 35-bed medico-surgical intensive care department in which antibiotic strategies are reviewed by infectious disease specialists three times per week Patients.dOne hundred sixty-nine patients with 216 episodes of severe sepsis attributable to a hospital-acquired infection who required broadspectrum b-lactam antibiotics alone or in association with other antiinfectious agents Measurements and Main Results.dThe major sources of infection were the lungs (44%) and abdomen (38%) Microbiological data were available in 167 of the 216 episodes (77%) Initial antimicrobial therapy was inappropriate in 27 episodes (16% of culture-positive episodes) De-escalation was applied in 93 episodes (43%), escalation was applied in 22 episodes (10%), mixed changes were applied in 24 (11%) episodes, and there was no change in empirical antibiotic therapy in 77 (36%) episodes In these 77 episodes, the reasons given for maintaining the initial antimicrobial therapy included the sensitivity pattern of the causative organisms and previous antibiotic therapy The number of episodes when the chance to de-escalate may have been missed was small (4 episodes [5%]) ... septic shock: beneficial or harmful? Shock 20 05 ;23 :51 6-5 20 Ryan M, Levy MM Clinical review: fever in intensive care unit patients Crit Care 20 03;7 :22 1 -2 25 Peres Bota D, Lopes Ferreira F, Me´lot... propensity-matched analysis Park DW, Chun B-C, Kwon S-S, et al (Korea Univ College of Medicine, Ansan; Korea Univ College of Medicine, Seoul; et al) Crit Care Med 40:314 0-3 145, 20 12 Objectives.dTo... propensity-matched analysis Park DW, Chun B-C, Kwon S-S, et al (Korea Univ College of Medicine, Ansan; Korea Univ College of Medicine, Seoul; et al) Crit Care Med 40:314 0-3 145, 20 12 Objectives.dTo