Postsplenectomy sepsis syndrome. How to identify and manage patients at risk

Established postsplenectomy sepsis syndrome, although infrequent, may carry a mortality rate of over 90%. Pneumococcus (Streptococcus pneumoniae) has been the infective organism in more than 50% of published cases. Certain groups, such as infants, patients with hematologic malignancy, and those with compromised humoral immunity, may be especially susceptible. However, even healthy individuals who have been splenectomized because of trauma may be affected. Within the general population there is a significant pool of asplenic or functionally hyposplenic patients who are not aware of their condition. Efforts must be made to identify any such individual at risk for the postsplenectomy sepsis syndrome. The new 23-valent polysaccharide pneumococcal vaccine should be made available to any asplenic or functionally hyposplenic individual. A high index of suspicion must be maintained for febrile illness in asplenic patients, and if such an illness occurs, a vigorous investigation is mandatory.     

Early drotrecogin alpha (activated) administration in severe sepsis is associated with lower mortality: a retrospective analysis of the Canadian ENHANCE cohort

Introduction  

Early multimodal treatment of severe sepsis, including the use of drotrecogin alfa (activated) (DrotAA) when indicated, is considered essential for optimum outcome. However, predicting which infected patients will progress to severe sepsis and the need for aggressive intervention continues to be problematic. We therefore wished to explore whether there were any potential early markers that might predict improved survival in response to early use of DrotAA in patients with severe sepsis. In particular, in the dynamic setting of severe sepsis, we postulated that changes in markers reflecting evolving rather than baseline clinical status might guide therapy.     

The usefulness of the semiquantitative procalcitonin test kit as a guideline for starting antibiotic administration

Objectives

The Surviving Sepsis Campaign has recommended that antibiotic therapy should be started within the first hour of recognizing severe sepsis. Procalcitonin has recently been proposed as a biomarker of bacterial infection, although the quantitative procalcitonin assay is often time consuming, and it is not always available in many emergency departments (EDs). Our aim is to evaluate usefulness of the semiquantitative procalcitonin fast kit as a guideline for starting antibiotic administration for patients with severe sepsis or septic shock that requires prompt antibiotic therapy in the ED.

Methods

We include those patients who were admitted to the ED and who were suspected of having infection. The procalcitonin concentration was determined by semiquantitative PCT-Q strips, and the points of the severity scoring system were calculated. The receiver operating characteristic curve was used to assess the diagnostic value of the PCT-Q strips to predict severe sepsis or septic shock.

Results

Of the 80 recruited patients, 33 patients were categorized as having severe sepsis or septic shock according to the definition. At a procalcitonin cutoff level of 2 ng/mL or greater, the sensitivity of the PCT-Q for detecting severe sepsis or septic shock was 93.94% and the specificity was 87.23. The receiver operating characteristic curve for PCT-Q to predict severe sepsis or septic shock had an area under the curve of 0.916.

Conclusion

PCT-Q is probably a fast, useful method for detecting severe sepsis in the ED, and it can be used as a guideline for antibiotic treatment.     

Alloimmune platelet transfusion refractoriness circumvented by allogeneic stem cell transplantation

BACKGROUND: Administration of intensive chemotherapy used in the management of malignancies is accompanied with marrow suppression. Patients undergoing such treatments and especially those with acute leukemia need prolonged blood component support and are at risk for platelet (PLT) refractoriness. Irradiated and filtered blood, although effective, does not eliminate the risk for refractoriness and consequent fatal hemorrhage. STUDY DESIGN AND METHODS: The current report presents a case of an acute myeloid leukemia patient who became alloimmunized to multiple HLA antigens after complicated autologous stem cell transplantation and to whom granulocytes were transfused as part of treatment for overwhelming sepsis. Poor engraftment necessitated prolonged transfusion dependency with rare HLA‐compatible donors detected according to the indirect PLT immunofluorescence test. During the proceeding weeks the patient suffered from recurrent severe attacks of gastrointestinal bleeding. When several conservative treatments failed, a fully HLA‐matched, bidirectionally ABO‐incompatible allogeneic transplantation from a sibling donor was performed. RESULTS: Allogeneic transplantation was uneventful, with stable full donor‐derived lymphohematopoietic engraftment. CONCLUSION: Immune PLT refractoriness can appear at later stages of treatment even in severely immunocompromised patients. Granulocyte transfusions could lead to alloimmunization and should therefore be cautiously considered in this patient population.     

Increases in serum macrophage migration inhibitory factor in patients with severe sepsis predict early mortality

This prospective study aimed to delineate the association between the serum levels of macrophage migration inhibitory factor (MIF) and the risks of early mortality in 112 patients who presented with clinically severe sepsis. Previous studies showed that elevated serum MIF levels on the first day are associated with an increased risk of 28-day mortality. Nonsurvivors may be the sickest population on arrival. Not all patients with severe sepsis follow the same clinical pathway, however, and the sequential change in MIF might be an important predictor of mortality. We hypothesized that, for septic patients, in addition to serum MIF levels on day 1, the percentage of change in MIF between days 1 and 2 after arriving in the emergency department predicts the probability of early mortality. Serum MIF levels were measured on days 1 (emergency department arrival) and 2 (24 h after arrival). Patients with a high percentage of increase between MIF levels on days 1 and 2 had higher 3-day (odds ratio, 1.8; 95% confidence interval, 1.2-2.6; P = 0.003) and 7-day mortalities (odds ratio, 1.4; 95% confidence interval, 1.0-1.9; P = 0.03) after adjusting for age and day-1 serum MIF levels. In conclusion, an increase in serum MIF from the first to second day of admission in patients with severe sepsis indicates a higher risk of early mortality; therefore, these patients need more aggressive therapeutic intervention.     

The septic syndrome. Definition and clinical implications

The septic syndrome can be defined using clinical criteria in patients with clinical evidence of an infectious process. The other criteria include fever or hypothermia, tachypnea, tachycardia, and evidence of impaired organ perfusion or function as manifested by either altered mentation, hypoxemia, elevated plasma lactate, or oliguria. A multicenter trial using these criteria found positive blood cultures in 45 per cent of 382 patients. The mortality rate was approximately 30 per cent and 25 per cent of the patients developed ARDS. With respect to these characteristics, this septic syndrome population was very similar to the more traditionally defined populations with sepsis. Using the septic syndrome definition may allow for earlier detection of septic patients and possibly allow for earlier therapeutic intervention. The septic syndrome may help identify a population of patients at risk for the various complications of sepsis (that is, ARDS), aid in the search for pathophysiologic mechanisms, and allow for pharmacological trials earlier in the disease process.     

Occult splenic rupture with cardiovascular collapse: a report of three cases in critically ill patients

Three cases of splenic rupture causing cardiovascular collapse in critically ill patients are discussed. The first patient had received cardiopulmonary resuscitation (CPR) in the days before the collapse, the second patient was recovering from severe sepsis and the third patient was recovering from severe sepsis, had received CPR and had undergone percutaneous endoscopic gastrostomy (PEG). The diagnosis was made at post mortem in two of the patients, the third patient, who bled following PEG, survived after prompt surgical intervention. Splenic rupture should be considered as part of the differential diagnosis of unexpected cardiovascular collapse in patients who have received CPR or who are recovering from sepsis.     

Procalcitonin as a diagnostic test for sepsis: health technology assessment in the ICU

Elevation in the serum concentration of procalcitonin (PCT) is associated with systemic infection. This association has led to the proposed use of PCT as a novel biomarker of bacterial sepsis. The advantages and limitations of the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) definitions of sepsis are an important consideration that affects the impact of any diagnostic test for sepsis and these issues are discussed. Our main objective is to perform a systematic health technology assessment of PCT as a diagnostic test for sepsis. In an adult intensive care unit (ICU) population, we identify a specific and important question-can PCT accurately distinguish sepsis in patients with systemic inflammatory response syndrome (SIRS) who have a suspected infection? Likelihood ratios are calculated from published data to attempt to find the best answer. The published evidence does not support a general claim that PCT is a useful decision support tool for diagnosing sepsis in patients who have SIRS. Procalcitonin has a slightly better ability to exclude the diagnosis of sepsis. The role for using PCT testing in the ICU will continue to evolve along with our understanding and definition of sepsis.     

Empiric therapy for the febrile neutropenic patient

Empiric therapy is practical and must be begun promptly; the specific regimen chosen must be based upon local conditions and epidemiology. It must be recalled that subgroups of patients are not necessarily equivalent to the majority, i.e., there are low-risk patients for whom ambulatory and/or oral therapy is appropriate and, conversely, there are high-risk patients who have a potential for a high mortality and who, while perhaps few in number, are of critical importance. Further, many of these patients are very complex, and this leads to a high level of physician concern and insecurity. This physician concern, in turn, leads to a tendency to modify regimens, given that the physician all too often is dealing with inadequate diagnostic information owing to the patient situation. The physician's choice of modification is highly dependent upon knowledge of the regimen the patient is already receiving. There is a need for clear definition of endpoints, and these must be established before the study is initiated. All too many published studies are too small to evaluate the endpoint that has been defined, and many others, although sufficient in size, have all of the problems inherent in studies conducted at multiple sites by multiple individuals with differing degrees of commitment or enthusiasm toward the study at hand. A few implications for study design and evaluation seem evident: it is critical to define endpoints and execute the study accordingly. This means determining the size of the population needed and determining the presence or absence of risk groups. Patients to be excluded e.g., those in whom infection is doubted must be selected on the basis of objective data by an observer blinded to both the outcome and the treatment. Similarly, the classification of response should preferably be done by an observer not influenced by knowledge of the therapy being given. Finally, and similarly, the decision to modify therapy (especially if modification is equivalent to defining failure with the regimen) should not be influenced by knowledge of the therapy being administered.     

Investigation of hemophagocytic lymphohistiocytosis in severe sepsis patients

PurposeHemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by uncontrolled inflammation and has common clinical and laboratory features with sepsis. The aim of this study was to investigate patients treated with severe sepsis who had bicytopenia for the presence of HLH.Materials and methodsPatients with severe sepsis who were non-responsive to treatment and developed at least bicytopenia were included. Peripheral blood samples were collected and stored for later evaluation for natural killer (NK) activity and soluble interleukin-2 receptor levels. Diagnostic criteria of HLH were retrospectively analyzed.ResultsSeventy-five of 382 patients (20%) were followed as severe sepsis and septic shock. Among them, 40 patients had bicytopenia. Twenty-six of 40 patients were excluded due to the presence of active solid or hematological malignancies. Three patients died before fulfillment of HLH criteria and one patient denied to give consent. All of the remaining 10 patients had at least five of the eight criteria according to criteria of the Histiocyte Society. Only one of 10 patients was diagnosed as HLH and received treatment during intensive care unit stay. None of the 10 patients survived.ConclusionsThis study emphasizes to consider the possibility of HLH and the need of rapid assessment of patients with severe sepsis who had bicytopenia and were resistant to treatment in intensive care.     

应激性心肌病1例分析

休克在重症患者中是很常见的,以往认为心源性休克多源自于急性冠状动脉事件,同时,感染性休克患者也可合并心肌抑顿,导致心源性休克。上述两种情况一旦出现,往往预后不良,但2007年初我们收治了1例心源性休克的患者,并不是由于急性心肌梗死或严重感染等情况所致,更富有戏剧性的是经过支持治疗,该患者的心脏功能在短期内完全恢复。经过文献回顾我们认为,患者应考虑合并了应激性心肌病,该疾病在重症医学领域少有报道,但由于此类患者的心脏功能经过积极干预可在短期内痊愈,此点不同于其他原因引起的心源性休克,故我们应提高对应激性心肌病的认识,早期诊断、积极干预,争取患者的良好预后。     

Long-term mortality after critical care: what is the starting point?

Mortality is still the most assessed outcome in the critically ill patient and is routinely used as the primary end-point in intervention trials, cohort studies, and benchmarking analysis. Despite this, interest in patient-centered prognosis after ICU discharge is increasing, and several studies report quality of life and long-term outcomes after critical illness. In a recent issue of Critical Care, Cuthbertson and colleagues reported interesting results from a cohort of 439 patients with sepsis, who showed high ongoing long-term mortality rates after severe sepsis, reaching 61% at 5 years (from a starting point of ICU admission). Follow-up may start at ICU admission, after ICU discharge, or after hospital discharge. Using ICU admission as a starting point will include patients with a wide range of illness severities and reasons for ICU admission. As a result, important consequences of the ICU, such as rehabilitation and reduced quality of life, may be diluted in an unselected population. ICU discharge is another frequently used starting point. ICU discharge is a marker of better outcome and reduced risk for acute deterioration, making this an interesting starting point for studying long-term mortality, need for ICU readmission, and critical illness rehabilitation. Finally, using hospital discharge as the starting point will include patients with the minimal requirements to sustain an adequate condition in a non-monitored environment but will add a ?survivors bias?; that is, patients who survive critical illness are a special group among the critically ill. In this commentary, we discuss the heterogeneity in long-term mortality from recent studies in critical care medicine ? heterogeneity that may be a consequence simply of changing the follow-up starting point ? and propose a standardized follow-up starting point for future studies according to the outcome of interest.     

Enteral nutrition with eicosapentaenoic acid, γ-linolenic acid and antioxidants in the early treatment of sepsis: results from a multicenter, prospective, randomized, double-blinded, controlled study: the INTERSEPT study

Introduction  

Enteral nutrition (EN) with eicosapentaenoic acid (EPA)/γ-linolenic acid (GLA) is recommended for mechanically ventilated patients with severe lung injury. EPA/GLA has anti-inflammatory benefits, as evidenced by its association with reduction in pulmonary inflammation, improvement in oxygenation and improved clinical outcomes in patients with severe forms of acute lung injury. This study was a prospective, multicenter, randomized, double-blinded, controlled trial designed to investigate whether EPA/GLA could have an effective role in the treatment of patients with early sepsis (systemic inflammatory response syndrome with confirmed or presumed infection and without any organ dysfunction) by reducing the progression of the disease to severe sepsis (sepsis associated with at least one organ failure) or septic shock (sepsis associated with hypotension despite adequate fluid resuscitation). Secondary outcomes included the development of individual organ failure, increased ICU and hospital length of stay, need for mechanical ventilation and 28-day all-cause mortality.     

Bench-to-bedside review: The evaluation of complex interventions in critical care

Complex interventions, such as the introduction of medical emergency teams or an early goal-directed therapy protocol, are developed from a number of components that may act both independently and inter-dependently. There is an emerging body of literature advocating the use of integrated complex interventions to optimise the treatment of critically ill patients. As with any other treatment, complex interventions should undergo careful evaluation prior to widespread introduction into clinical practice. During the development of an international collaboration of researchers investigating protocol-based approaches to the resuscitation of patients with severe sepsis, we examined the specific issues related to the evaluation of complex interventions. This review outlines some of these issues. The issues specific to trials of complex interventions that require particular attention include determining an appropriate study population and defining current treatments and outcomes in that population, defining the study intervention and the treatment to be used in the control group, and deploying the intervention in a standardised manner. The context in which the research takes place, including existing staffing levels and existing protocols and procedures, is crucial. We also discuss specific details of trial execution, in particular randomization, blinded outcome adjudication and analysis of the results, which are key to avoiding bias in the design and interpretation of such trials. These aspects of study design impact upon the evaluation of complex interventions in critical care. Clinicians should also consider these specific issues when implementing new complex interventions into their practice.     

Early detection of heterotopic ossification in young patients with traumatic brain injury.

Heterotopic ossification (HO) is frequently a complication in patients with severe head injury, impeding the rehabilitation process. Detection of HO is often delayed until the appearance of clinical manifestations. To better characterize the frequency and distribution of HO, a three-year prospective study at a pediatric brain injury rehabilitation unit was done. Triple-phase bone scans were performed routinely on all patients. Early intervention followed, with intensive physical therapy and indomethacin. We report an incidence of HO in 25 of 111 cases (22.5%). Of 55 sites identified, the hip was most commonly affected. Clinically significant heterotopic bone impeded the rehabilitation process in five patients (20%), although none of these patients required surgical intervention. Bone scanning identified HO in patients whose symptoms were clinically silent, as well as in those who were symptomatic. In addition, multiple sites of involvement were found in areas not clinically suspect. This study suggests that HO may be more prevalent in young, traumatically brain injured patients than previously suspected.     

Mediators of septic lung injury

Septic pulmonary injury remains a significant cause of morbidity and mortality among hospitalized patients today and is likely to increase in prevalence as advances in medical technology allow the salvage of more critically ill and immunocompromised hosts. Treatment of the host's underlying disease and even of the infection itself has appeared to redeem septic patients only to have them succumb in increasing numbers to the pulmonary injury reaction. Our understanding of the mechanisms and mediators of lung dysfunction in sepsis is in a rapidly expanding phase. Currently we recognize the contributions of several blood elements, lipids, and peptides to pulmonary injury, although the relative importance and points of interaction and interdependence of these mediators remain to be established. It is hoped that a more complete understanding of the process of pulmonary injury in sepsis will suggest effective means of intervention at a stage in which damage may be reversed or minimized.     

Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: a trend analysis from 1993 to 2003

OBJECTIVE: To determine recent trends in rates of hospitalization, mortality, and hospital case fatality for severe sepsis in the United States. DESIGN: Trend analysis for the period from 1993 to 2003. SETTING: U.S. community hospitals from the Nationwide Inpatient Sample that is a 20% stratified sample of all U.S. community hospitals. PATIENTS: Subjects of any age with sepsis including severe sepsis who were hospitalized in the United States during the study period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Utilizing International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for septicemia and major organ dysfunction, we identified 8,403,766 patients with sepsis, including 2,857,476 patients with severe sepsis, who were hospitalized in the United States from 1993 to 2003. The percentage of severe sepsis cases among all sepsis cases increased continuously from 25.6% in 1993 to 43.8% in 2003 (p < .001). Age-adjusted rate of hospitalization for severe sepsis grew from 66.8 +/- 0.16 to 132.0 +/- 0.21 per 100,000 population (p < .001). Age-adjusted, population-based mortality rate within these years increased from 30.3 +/- 0.11 to 49.7 +/- 0.13 per 100,000 population (p < .001), whereas hospital case fatality rate fell from 45.8% +/- 0.17% to 37.8% +/- 0.10% (p < .001). During each study year, the rates of hospitalization, mortality, and case fatality increased with age. Hospitalization and mortality rates in males exceeded those in females, but case fatality rate was greater in females. From 1993 to 2003, age-adjusted rates for severe sepsis hospitalization and mortality increased annually by 8.2% (p < .001) and 5.6% (p < .001), respectively, whereas case fatality rate decreased by 1.4% (p < .001). CONCLUSIONS: The rate of severe sepsis hospitalization almost doubled during the 11-yr period studied and is considerably greater than has been previously predicted. Mortality from severe sepsis also increased significantly. However, case fatality rates decreased during the same study period.     

Frequency of severe attacks in migraine sufferers of the Gazel cohort

The concept of severe migraine was raised to define migraineurs most in need of care and for use in clinical practice. We aimed to measure the frequency of severe attacks in a working sample of 276 migraine sufferers using a diary over a 3-month period. Migraine sufferers recorded each attack's clinical features, the degree of their disability, their use of drugs and the effectiveness of the drugs. Since the definition of severe attack is not standardized, we studied the impact of different definitions on the frequency. The frequency of severe attacks was 0.9% and appeared to be very sensitive to the definitions, ranging between 0.4 and 13%. In France, the extrapolated number of severe attacks is nearly one million out of a total of 115 million. In the migraineurs who had had at least one severe attack, the individual variability of intensity, duration or disability was very high, so the proportion of severe attacks in a given sufferer was low-between 15% and 50%. We conclude that the global concept of severe migraine is not relevant and should be split into two componentssevere attack and severe migraine sufferer. The goals are different, too. Regarding treatment, for example, the severe attack concept is more valid for acute treatment strategies, whereas the severe migraine sufferer concept should be preferred to determine the need for prophylactic treatment. Since much work is being done nowadays to define a rate treatment strategies, definition of the criteria of severe attack and validation of a measurement tool should be a priority.     

qSOFA Has Poor Sensitivity for Prehospital Identification of Severe Sepsis and Septic Shock

Objectives: Sepsis is a common and deadly disease process for which early recognition and intervention can significantly improve clinical outcomes. Despite this, sepsis remains underrecognized and therefore undertreated in the prehospital setting. Recent recommendations by the Society of Critical Care and European Society of Intensive Care Medicine advocate use of the qSOFA (quick Sequential [Sepsis-related] Organ Failure Assessment) score in non-ICU settings to screen for septic patients at greater risk for poor outcomes. Methods: We retrospectively evaluated the sensitivity and specificity of a prehospital qSOFA score ≥ 2 for prehospital identification of patients with severe sepsis or septic shock. Emergency Department (ED) patients with confirmed or suspected infection were classified as having infection without sepsis (n = 71), sepsis (n = 38), or severe sepsis/septic shock (n = 43), where designation of severe sepsis/septic shock required evidence of end-organ dysfunction, hypoperfusion (lactate > 2), or vasopressor requirement. Results: We found that a prehospital qSOFA score ≥ 2 was 16.3% sensitive (95% CI 6.8–30.7%) and 97.3% specific (95% CI 92.1–99.4%) for patients ultimately confirmed to have severe sepsis/septic shock in the ED. Adding an additional point to the prehospital qSOFA score for a pulse > 100, nursing home residence, age > 50, or reported fever increased the sensitivity to 58.1% (95% CI 42.1–73.0%) and decreased the specificity to 78.0% (95% CI 69.0–85.4%). During their ED stay, approximately two-thirds of patients meeting severe sepsis/septic shock criteria eventually met qSOFA criteria with a sensitivity of 67.4% (95% CI 51.5–80.9) and specificity of 86.2% (95% CI 78.3–92). Failure to meet qSOFA criteria prehospital was predominantly due to a systolic blood pressure and respiratory rate that did not yet meet predetermined thresholds. Conclusions: These findings suggest that the dynamic nature of sepsis can make sensitive detection difficult in the prehospital setting, although combining qSOFA with other clinical information (age, nursing home status, fever, and tachycardia) can identify more patients with sepsis who may benefit from time critical interventions.