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Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine.
Abstract
An American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference was held in Northbrook in August 1991 with the goal of agreeing on a set of definitions that could be applied to patients with sepsis and its sequelae. New definitions were offered for some terms, while others were discarded. Broad definitions of sepsis and the systemic inflammatory response syndrome were proposed, along with detailed physiologic parameters by which a patient may be categorized. Definitions for severe sepsis, septic shock, hypotension, and multiple organ dysfunction syndrome were also offered. The use of severity scoring methods when dealing with septic patients was recommended as an adjunctive tool to assess mortality. Appropriate methods and applications for the use and testing of new therapies were recommended. The use of these terms and techniques should assist clinicians and researchers who deal with sepsis and its sequelae.
... Sepsis is defined as a syndrome of life-threatening organ dysfunction caused by a dysregulated host response to infection. 1 The Global Sepsis Alliance has proposed that adults aged older than 60 years have a higher risk of sepsis than those in the general population. 2 The guidelines Sepsis-1 3 and Sepsis-2 4 delineate sepsis and associated conditions through the utilization of the Systemic Inflammatory Response Syndrome (SIRS). However, SIRS lacks specificity and does not provide a prognostic determination. ...
... 2,17 Suspicion of sepsis was operationalized as patients presenting with the primary complaint of fever and exhibiting clinical indicators of infection, such as extreme shivering or muscle pain, fever, purulent or productive sputum, pyuria, and signs of soft tissue infection. [2][3][4]14,17 In accordance with the ED sepsis protocol, inclusion criteria encompassed adult patients with a physician's suspicion of infection. This included cases where the site of infection was identified or when the physician strongly suspected sepsis, even in instances where REWS was below four. ...
... The final diagnosis of sepsis in our cohort was defined as patients diagnosed with sepsis based on International Classification of Diseases, 10th edition (ICD-10) codes or clinical assessment by attending physicians, 1,2 as well as patients diagnosed through positive blood culture, body fluid culture, or specimen culture. 3,4,14,17 Sepsis is primarily a clinical diagnosis. However, in patients with uncertain clinical presentations, culture results can aid in identifying the causative organism and guiding appropriate antimicrobial therapy. ...
Background
Older patients face increased sepsis risk, requiring precise prognostic tools in the emergency department (ED). This study aimed to explore factors predicting 28‐day mortality among older (≥60 years) patients with suspicion of sepsis in the ED.
Methods
We performed a retrospective cohort study. Data for all older patients with clinical suspected sepsis presenting to the ED from 1 October 2018 to 31 December 2018, were collected. Prognostic factors, characteristics, comorbidities, vital signs at triage, the emergency severity score, initial laboratory results, and sepsis bundle treatment were analyzed using univariable and multivariable Cox regression. Hazard ratios (HR) were calculated using these analytical methodologies to prognosticate 28‐day mortality.
Results
A total of 329 older patients with suspected sepsis were included. The overall 28‐day mortality was 10.33%. Independent prognostic factors that were significantly associated with 28‐day mortality were malignancy (adjusted hazard ratio [aHR]: 3.67; 95% confidence interval [CI]: 1.90, 7.09; p < 0.01), oxygen saturation ≤93% (aHR: 3.37; 95% CI: 1.79, 3.43; p < 0.01), and dependent status (hazard ratio [HR]: 2.27; 95% CI: 1.14, 4.53; p = 0.02).
Conclusions
This study suggests that “MOD”; M‐Malignancy, O‐Oxygen saturation ≤93%, and D‐Dependent status are significant prognostic indicators for 28‐day mortality among older patients with suspected sepsis in the ED.
Trial registration
The trial was retrospectively registered in the Thai Clinical Trial Registry on 06/05/2022, identification number TCTR20220506006.
... Due to the original study design, critically ill patients with either a continuous SIRS status [50] for two consecutive days or patients fulfilling sepsis criteria of the sepsis-1/2 definition but not severe sepsis or septic shock [50] within the first 24 h after ICU admission were included. Exclusion criteria were age < 18 years, immunosuppression, end-stage renal failure, pregnancy, ECMO therapy, and neurosurgical main diagnosis to exclude confounding neuroinflammation. ...
... Due to the original study design, critically ill patients with either a continuous SIRS status [50] for two consecutive days or patients fulfilling sepsis criteria of the sepsis-1/2 definition but not severe sepsis or septic shock [50] within the first 24 h after ICU admission were included. Exclusion criteria were age < 18 years, immunosuppression, end-stage renal failure, pregnancy, ECMO therapy, and neurosurgical main diagnosis to exclude confounding neuroinflammation. ...
Tissue hypoxia is associated with the development of organ dysfunction and death in critically ill patients commonly captured using blood lactate. The kinetic parameters of serial lactate evaluations are superior at predicting mortality compared with single values. S-adenosylhomocysteine (SAH), which is also associated with hypoxia, was recently established as a useful predictor of septic organ dysfunction and death. We evaluated the performance of kinetic SAH parameters for mortality prediction compared with lactate parameters in a cohort of critically ill patients. For lactate and SAH, maxima and means as well as the normalized area scores were calculated for two periods: the first 24 h and the total study period of up to five days following ICU admission. Their performance in predicting in-hospital mortality were compared in 99 patients. All evaluated parameters of lactate and SAH were significantly higher in non-survivors compared with survivors. In univariate analysis, the predictive power for mortality of SAH was higher compared with lactate in all forms of application. Multivariable models containing SAH parameters demonstrated higher predictive values for mortality than models based on lactate parameters. The optimal models for mortality prediction incorporated both lactate and SAH parameters. Compared with lactate, SAH displayed stronger predictive power for mortality in static and dynamic application in critically ill patients.
... These physiological changes bear similarities to those observed in other types of injuries, such as burns, infections, and traumatic injuries. The response to surgery or other traumas is commonly referred to as the systematic inflammatory response syndrome [34]. The stress response to surgery is typically divided into two phases: the "ebb" and "flow." ...
... These physiological changes bear similarities to those observed in other types of injuries, such as burns, infections, and traumatic injuries. The response to surgery or other traumas is commonly referred to as the systematic inflammatory response syndrome [34]. The stress response to surgery is typically divided into two phases: the "ebb" and "flow". ...
This paper aims to provide an in-depth review of the specific outcomes associated with omega-3 polyunsaturated fatty acids (PUFAs), focusing on their purported effects on post-surgical complications in trauma patients. A comprehensive investigation of omega-3 polyunsaturated fatty acids was conducted until February 2023 using the PubMed database. Surgical trauma is characterized by a disruption in immune response post surgery, known to induce systemic inflammation. Omega-3 PUFAs are believed to offer potential improvements in multiple post-surgical complications because of their anti-inflammatory and antioxidant properties. Inconsistent findings have emerged in the context of cardiac surgeries, with the route of administration playing a mediating role in these outcomes. The effects of omega-3 PUFAs on post-operative atrial fibrillation have exhibited variability across various studies. Omega-3 PUFAs have demonstrated positive effects in liver surgery outcomes and in patients with acute respiratory distress syndrome. Omega-3 is suggested to offer potential benefits, particularly in the perioperative care of patients undergoing traumatic procedures. Incorporating omega-3 in such cases is hypothesized to contribute to a reduction in certain surgical outcomes, such as hospitalization duration and length of stay in the intensive care unit. Therefore, comprehensive assessments of adverse effects can aid in identifying the presence of subtle or inconspicuous side effects associated with omega-3.
... A previous study also found that culture-positive patients had a higher HR (108 vs. 83, P<0.001) than culture-negative patients [7]. Sepsis is characterized by a RR of more than 20 breaths per minute [23]. In this study, more patients with negative cultures had tachypnea (RR of more than 20 breaths per minute). ...
... Elevated TLC levels with thrombocytopenia were higher in the culture-positive group, which is consistent with a previous study demonstrating that patients with a positive culture often had higher infection indicators in their WBC counts (13.7 vs. 10.5, P<0.001) [7]. Previous studies have shown that a WBC count of more than 12x10⁹/L and less than 4x10⁹/L implies sepsis [23]. Furthermore, in this study, a higher proportion of patients with a positive culture had a significantly deranged PT/INR than patients with a negative culture. ...
... In this study, most patients were males. This is consistent with the demographic pattern of burn populations in recent epidemiological studies [15,16]. Moreover, Staphylococcus aureus was the most common infective organism isolated from burn wound cultures. ...
... SIRS criteria were defined as follows: heart rate (HR) > 90/ min, respiratory rate (RR) > 20/min, temperature (T) <36°C or >38°C, and white blood cell count (WBC) <4×10 9 /L or >12×10 9 /L. A positive result was defined as ≥2 out of 4 possible signs 14 . ...
... Индукция СВР, согласно множеству исследований, может осуществляться по пути так называемого danger-сигнала за счет активации патоген-распознающих рецепторов (Toll-подобные и NOD-подобные рецепторы) лигандами, большинство из которых считается классическими сигнальными молекулами критического состояния (так называемые патоген-ассоциированные молекулярные паттерны, представителем которых является липополисахарид и эндогенные, ассоциированные молекулярные паттерны или алармины -белок S100, белки теплового шока, HMGB-1 и другие). В свое время «теория опасности» -набор постулатов, формально предложенных Полли Матцингер, -был революционным прорывом в иммунологии [1,2]. Теория объясняет, что иммунные реакции могут происходить вне инфекционного агента, что объясняло эволюцию иммунной системы не как распознавание «своего/чужого», а в том числе и как реакцию на повреждение тканей (инфекция vs стерильное воспаление). ...
Comment on the article of L.A. Krichevskiy et al. “Systemic inflammatory response syndrome after on-pump cardiac surgery in emergency coronary artery bypass grafting: a retrospective trial”
... Patients suffering from septic shock can be identi ed clinically by low mean arterial pressure of Less than 65 mmHg, unresponsive to intravenous uid administration, and serum lactate elevation of more than 2 mmol/L in the absence of hypovolemia. [2] Respiratory and abdominal infections are the most common causes of sepsis, followed by urinary tract and soft tissue infections. [3] The purpose of this review is to evaluate the awareness of medical students in Syrian private university about septic shock. ...
Background
Shock is a condition of inadequate tissue perfusion resulting in decreased oxygen and metabolic requirements. It can lead to disturbance in energy production changes in cellular metabolism and significant acidosis. Various body systems are exposed to dysfunction and sometimes death if appropriate and intensive therapeutic measures are not taken early. Septic shock is the common final pathway by which many diseases and deaths occur.
Research Materials and Methods
A retrospective cohort study (COHORT) was conducted On a random group of elderly patients after surgery from June 2023 to February 2025.
A questionnaire was conducted and the individuals participating at the Syrian Private University were followed up during the research period. Accordingly, the questionnaire was filled out and the data was reviewed under the supervision of the research supervisor
Results
The sample included 240 patients, of which 20 were excluded, leaving us with 220 cases on which research and statistics were conducted. 39.5% were females and 60.5% were males. Participants are classified into five age groups, with the age group (20 – 21) years representing 24.1% (mean 76 years), and participants in the age group (22 – 23) were 50%.
79.5% of students believed that advanced age was a risk factor for septic shock.
Conclusion
It is necessary to hold medical seminars on sepsis and explain the difference between its types, as well as publish awareness campaigns on the necessity of educating medical staff, especially students, doctors, and nurses, about sepsis, its types, and ways to deal with it.
... These dysfunctions can include increased heart and respiratory rate, temperature, leukopenia, or leukocytosis. During the same period, septic shock was described as hypotension and persistent organ dysfunction, even with the use of volume and the need for vasopressor administration [17]. ...
Sepsis and acute kidney injury (AKI) are two major public health concerns that contribute significantly to illness and death worldwide. Early diagnosis and prompt treatment are essential for achieving the best possible outcomes. To date, there are no specific clinical, imaging, or biochemical indicators available to diagnose sepsis, and diagnosis of AKI based on the KDIGO criterion has limitations. To improve the diagnostic process for sepsis and AKI, it is essential to continually evolve our understanding of these conditions. Delays in diagnosis and appropriate treatment can have serious consequences. Sepsis and AKI often occur together, and patients with kidney dysfunction are more prone to developing sepsis. Therefore, identifying potential biomarkers for both conditions is crucial. In this review, we talk about the main biomarkers that evolve the diagnostic of sepsis and AKI, namely neutrophil gelatinase-associated lipocalin (NGAL), proenkephalin (PENK), and cell-free DNA.
... Sepsis definition has changed over the last few decades. The first proposed definition and diagnosis of sepsis was based on the SIRS criteria, which is referred to as Sepsis-1 (12,13). Because of the low specificity of the SIRS criteria and due to the common occurrence of sepsis-induced OD that is strongly related to worse outcomes, the current definition of sepsis in humans emphasizes the presence of organ system failure or dysfunction. ...
Introduction
Sepsis in people is defined as a life-threatening organ dysfunction (OD) caused by a dysregulated host response to infection. In veterinary medicine, sepsis is still defined by the presence of systemic inflammation plus the evidence of infection. Based on recent veterinary studies, multiorgan dysfunction syndrome (MODS) has been associated with a worse outcome in sepsis. Thus, the screening for OD is warranted to identify the most critically ill patients. The aim of this study was to investigate the diagnostic value of new-onset OD for the prediction of sepsis and outcome in a population of critically ill dogs with systemic inflammation.
Materials and methods
Dogs admitted to the Emergency Room and/or the Intensive Care Unit with systemic inflammation, defined by a serum C-reactive protein concentration > 1.6 mg/dL, were retrospectively included. Enrolled dogs were categorized according to the presence of sepsis or non-infectious systemic inflammation. The presence of newly diagnosed OD was assessed based on criteria adapted from human literature and previously reported canine criteria.
Results
275 dogs were included: 128 had sepsis and 147 had non-infectious systemic inflammation. The frequency of new-onset OD was not different between these groups. Only the presence of fluid-refractory hypotension was significantly associated with a diagnosis of sepsis (OR 10.51, 3.08–35.94; p < 0.0001). The frequency of at least two ODs was significantly higher in non-survivors compared to survivors, according to both the human and the veterinary criteria considered for the study (p = 0.0001 and p = 0.0004, respectively). Specifically, the presence of acute kidney injury, stupor or coma, prolonged Prothrombin Time and decreased Base Excess were associated with a higher risk of death in the multivariate binary logistic regression.
Discussion
In this population of critically ill dogs with systemic inflammation, the detection of newly diagnosed ODs was not able to predict sepsis diagnosis, other than the presence of fluid-refractory hypotension. However, given the strong prognostic significance associated with ODs, our results support the early screening for ODs in any severe inflammatory critical care condition to identify high-risk patients and optimize their management.
... We collected components of SOFA and systemic inflammatory response syndrome (SIRS) criteria with timestamps to assess timing of multiple infectious and organ dysfunction measures. 15 16 as timestamps at which physicians may suspect sepsis ("sepsis recognition criteria"). Timestamps of vasopressor and antibiotic administration were obtained along with blood culture results. ...
Objective
Recent clinical guidelines for sepsis management emphasize immediate antibiotic initiation for suspected septic shock. Though hypotension is a high‐risk marker of sepsis severity, prior studies have not considered the precise timing of hypotension in relation to antibiotic initiation and how clinical characteristics and outcomes may differ. Our objective was to evaluate antibiotic initiation in relation to hypotension to characterize differences in sepsis presentation and outcomes in patients with suspected septic shock.
Methods
Adults presenting to the emergency department (ED) June 2012–December 2018 diagnosed with sepsis (Sepsis‐III electronic health record [EHR] criteria) and hypotension (non‐resolving for ≥30 min, systolic blood pressure <90 mmHg) within 24 h. We categorized patients who received antibiotics before hypotension (“early”), 0–60 min after (“immediate”), and >60 min after (“late”) treatment.
Results
Among 2219 patients, 55% received early treatment, 13% immediate, and 32% late. The late subgroup often presented to the ED with hypotension (median 0 min) but received antibiotics a median of 191 min post‐ED presentation. Clinical characteristics notable for this subgroup included higher prevalence of heart failure and liver disease ( p < 0.05) and later onset of systemic inflammatory response syndrome (SIRS) criteria compared to early/immediate treatment subgroups (median 87 vs. 35 vs. 20 min, p < 0.0001). After adjustment, there was no difference in clinical outcomes among treatment subgroups.
Conclusions
There was significant heterogeneity in presentation and timing of antibiotic initiation for suspected septic shock. Patients with later treatment commonly had hypotension on presentation, had more hypotension‐associated comorbidities, and developed overt markers of infection (eg, SIRS) later. While these factors likely contribute to delays in clinician recognition of suspected septic shock, it may not impact sepsis outcomes.
OBJECTIVES
Although clinicians may use methylene blue (MB) in refractory septic shock, the effect of MB on patient-important outcomes remains uncertain. We conducted a systematic review and meta-analysis to investigate the benefits and harms of MB administration in patients with septic shock.
DATA SOURCES
We searched six databases (including PubMed, Embase, and Medline) from inception to January 10, 2024.
STUDY SELECTION
We included randomized clinical trials (RCTs) of critically ill adults comparing MB with placebo or usual care without MB administration.
DATA EXTRACTION
Two reviewers performed screening, full-text review, and data extraction. We pooled data using a random-effects model, assessed the risk of bias using the modified Cochrane tool, and used Grading of Recommendations Assessment, Development, and Evaluation to rate certainty of effect estimates.
DATA SYNTHESIS
We included six RCTs (302 patients). Compared with placebo or no MB administration, MB may reduce short-term mortality (RR [risk ratio] 0.66 [95% CI, 0.47–0.94], low certainty) and hospital length of stay (mean difference [MD] –2.1 d [95% CI, –1.4 to –2.8], low certainty). MB may also reduce duration of vasopressors (MD –31.1 hr [95% CI, –16.5 to –45.6], low certainty), and increase mean arterial pressure at 6 hours (MD 10.2 mm Hg [95% CI, 6.1–14.2], low certainty) compared with no MB administration. The effect of MB on serum methemoglobin concentration was uncertain (MD 0.9% [95% CI, –0.2% to 2.0%], very low certainty). We did not find any differences in adverse events.
CONCLUSIONS
Among critically ill adults with septic shock, based on low-certainty evidence, MB may reduce short-term mortality, duration of vasopressors, and hospital length of stay, with no evidence of increased adverse events. Rigorous randomized trials evaluating the efficacy of MB in septic shock are needed.
REGISTRATION
Center for Open Science (https://osf.io/hpy4j).
Purpose
This study aims to discuss the management challenges of huge hydrocephalus (HH), a severe subset of hydrocephalus, presenting predominantly in underprivileged backgrounds. Insights into the condition’s characteristics, factors affecting outcomes, and associated morbidity are discussed.
Methods
A retrospective review of all operated cases of hydrocephalus with head circumference greater than body length (HC>L) was conducted (January 2019–January 2023). Data on epidemiological parameters, associated cranial abnormalities, cortical mantle thickness, peri-conceptional folic acid intake, surgical interventions, age-appropriate milestones, and complications were collected. Follow-up was conducted for at least 12 months or until expiration.
Results
The cohort consisted of 7 males and 5 females with age ranging from 3 to 48 months. 33% of them had associated neurological abnormalities, and 18 surgical interventions were needed for these 12 cases, including ventriculoperitoneal shunt or endoscopic diversion. A 17% wound breakdown rate requiring re-suturing was present, and 33% of cases had postoperative CSF infection, with 33% mortality, with only one case having age-appropriate development seen. The average hospital stay was 11.9 days, six times our center’s average. All cases with an Evans index with an average of 0.7 expired within 12 months. None of the 12 mothers took peri-conceptional folic acid, and no case agreed to reduction cranioplasty.
Conclusion
Huge hydrocephalus is a rare cohort with significant management challenges and poor prognosis even after treatment. Factors such as delayed intervention and low socioeconomic status contribute to adverse outcomes. Prevention through peri-conceptual folic acid intake and addressing socioeconomic disparities is crucial in reducing disease burden and improving prognosis.
Background
Sepsis remains a worldwide major cause of hospitalization, mortality, and morbidity. To enhance the identification of patients with suspected sepsis at high risk of mortality and adverse outcomes in the emergency department (ED), the use of mortality predictors is relevant. This study aims to establish whether quick sofa (qSOFA) and the severity criteria applied in patients with suspicion of sepsis in a monitored ED are in fact predictors of mortality.
Methods
We performed a retrospective cohort study among adult patients with suspicion of sepsis at the ED of a tertiary care hospital in Brazil between January 1st, 2019 and December 31, 2020. All adult patients (ages 18 and over) with suspected sepsis that scored two or more points on qSOFA score or at least one point on the severity criteria score were included in the study.
Results
The total of patients included in the study was 665 and the average age of the sample was 73 ± 19 years. The ratio of men to women was similar. Most patients exhibited qSOFA ≥ 2 (58.80%) and 356 patients (53.61%) scored one point in the severity criteria at admission. The overall mortality rate was 19.7% (131 patients) with 98 patients (14.74%) having positive blood cultures, mainly showing Escherichia coli as the most isolated bacteria. Neither scores of qSOFA nor the severity criteria were associated with mortality rates, but scoring any point on qSOFA was considered as an independent factor for intensive care unit (ICU) admission (qSOFA = 1 point, p = 0.02; qSOFA = 2 points, p = 0.03, and qSOFA = 3 points, p = 0.04). Positive blood cultures (RR, 1.63;95% CI, 1.10 to 2.41) and general administration of vasopressors at the ED (RR, 2.14;95% CI, 1.44 to 3.17) were associated with 30-day mortality. The administration of vasopressors at the ED (RR, 2.25; CI 95%, 1.58 to 3.21) was found to be a predictor of overall mortality.
Conclusions
Even though an association was found between qSOFA and ICU admission, there was no association of qSOFA or the severity criteria with mortality. Therefore, patients with a tendency toward greater severity could be identified and treated more quickly and effectively in the emergency department. Further studies are necessary to assess novel scores or biomarkers to predict mortality in sepsis patients admitted to the ED’s initial care.
When the concept of complicated and uncomplicated UTI was developed, new antibiotics were introduced almost every year, and the main objective of the classification was to facilitate the design of research protocols to study the effect of new antibiotics and decide the dosing and duration of treatment. The most widely used classifications of UTI are those developed by the Centre for Disease Control and Prevention in USA (CDC) in 1988 and updated in 2008, IDSA in 1992, and ESCMID in 1993. The new era with increasing antimicrobial resistance and need for antimicrobial stewardship calls for a more differentiated assessment of patients and tailoring of treatment according to the concept of personalized medicine. In an attempt to meet this need, the ORENUC classification was introduced by the European Section of Infections I Urology in 2010. In recognition of the characteristics of risk factors relevant for the three infections cystitis, pyelonephritis, and urosepsis, we organized the risk factors into six groups and proposed the ORENUC system for phenotyping. Today, it is time for an ESIU-ORENUC II classification that includes new findings and insights such as metagenomics and collateral effects of antibiotics, mathematical modeling, artificial intelligence, and modern communication technology to facilitate bedside decision-making.
Objectives: This research is designed to analyze the relationship between Sayeok-tang (四逆湯) and systemic inflammatory response syndrome in literature.Methods: The main treatment symptoms of Sayeok-tang (四逆湯) presented in Sanghanron(傷寒論) and Geumgweyoryak (金匱要略), and the symptoms of Ju-hwang(走黃) and Nae-ham(內陷), which is a sepsis and systemic inflammatory response syndrome in Korean medicine were analyzed. The symptoms of systemic inflammatory response syndrome presented in the related researches including diagnosis criteria and international guideline presented at the consensus conference hosted by the American College of Chest Physicians and The Society of Critical Care Medicine were also compared and analyzed.Results: The main treatment symptoms of Sayeok-tang (四逆湯) and symptoms of systemic inflammatory response were very similar, and were almost identical to the symptoms of Nae-ham (內陷, especially Gun-ham (乾陷) and Heo-ham(虛陷)), which are the Korean medicine descriptions of sepsis and systemic inflammatory response syndrome.Conclusions: Based on the research results, Sayeok-tang (四逆湯) can be used as a treatment of systemic inflammatory response syndrome.
Background: Percutaneous nephrolithotomy (PCNL) is commonly used in the treatment of large renal stones. Postoperative infections are a common consequence of these procedures. Objectives: The purpose of this study is to evaluate the effects of antibiotic therapy before PCNL on the possibility of developing fever and common complications after the procedure. Methods: We carried out a retrospective cross-sectional study involving 708 patients who had undergone PCNL at Razi Hospital in Rasht, covering the period from 2012 to 2022. Patients were allocated into two groups: Group 1 included 454 patients who had received antibiotic therapy, and group 2 included 254 patients who had not received pre-operative antibiotic therapy. Results: In group 1, there were 241 males (53.1%) and 213 females (46.9%), while in group 2, there were 138 males (54.3%) and 116 females (45.7%). In group 1, 82.7% of patients treated with antibiotics had a negative culture. The hospitalization time was 4.00 ± 1.75 days for group 1 and 2.26 ± 1.56 days for group 2. Fever was observed in 39 patients (11.2%) in group 1. Sepsis was seen in only one patient (0.3%) in group 1. There is a significant relationship between total hospitalization time (P = 0.000), hospitalization after the operation (P = 0.000), hypertension (P = 0.009), ischemic heart disease (P = 0.050), history of shock wave lithotripsy (P = 0.003), hydronephrosis (P = 0.000), age (P = 0.004), and hemoglobin levels (P = 0.000) with antibiotic therapy. Conclusions: Surgeon overprescription of antibiotics may lead to resistance, complicating outcomes and extending hospital stays after PCNL. Some complications remain unaffected by antibiotic therapy due to surgical experience.
Purpose: The prognostic performance of urea-to-albumin ratio (UAR) has been assessed in various pulmonary and nonpulmonary conditions, but never in thoracic empyema. Therefore, our aim was to determine whether this marker has the ability to predict outcome in such patients.Methods: A single-center retrospective study was conducted in a Clinic of Thoracic Surgery at a University Hospital between January 2021 and October 2023. A total of 84 patients who underwent emergency surgery due to thoracic empyema were involved. Serum levels of urea and albumin at admission were used to calculate UAR. We analyzed area under receiver operating characteristics (AUROC) curves of UAR, systemic inflammatory response syndrome (SIRS) and quick-sequential organ failure assessment (qSOFA), and compared their prognostic performance.Results: The identified in-hospital mortality was 10.7%. The UAR showed the best ability to prognosticate mortality compared to qSOFA (AUROC = 0.828 vs 0.747) and SIRS (AUROC = 0.828 vs 0.676). We established a sensitivity of 87.5% and specificity of 74.2% at optimal cut-off value UAR > 51.1 for prediction of adverse outcome.Conclusion: In patients with thoracic empyema urea-to-albumin ratio showed significant prognostic performance and a potential for clinical application as a low cost and widely available predictor of death.
Introduction: A prolonged operative time of lithotripsy with ureteroscopy for urolithiasis increases the risk of infectious complications; however, few reports have investigated the factors prolonging the operative time for ureteral stones. We investigated the factors associated with longer operative time in ureteroscopy for ureteral stones. Methods: This retrospective cohort study analyzed patients who underwent retrograde ureteroscopic lithotripsy for ureteral stones and achieved an endoscopic stone-free status between April 2019 and July 2022. Patients were classified into two groups based on an operative time of ≥90 minutes or <90 minutes. We compared the patient and stone characteristics and surgical outcomes, and investigated the factors associated with a prolonged operative time. Results: The cohort comprised 519 patients, with 58 patients in the group with an operative time of ≥90 minutes. Compared to the shorter operative time group, the longer operative time group had a significantly greater proportion of males, stone diameter, stone volume, and Hounsfield units of stone; additionally, the longer operative time group had higher prevalences of endoscopic findings of edema, polyps, and mucosa-stone adherence. Multivariable analysis showed that stone size >10 mm (odds ratio 4.05), polyps (odds ratio 2.40), and mucosal adherence (odds ratio 3.51) were significantly associated with an operative time exceeding 90 minutes. There were no significant differences between the two groups in the incidences of postoperative fever and systemic inflammatory response syndrome. Conclusions: Stone size, endoscopic findings of polyps, and mucosa-stone adherence were independent factors associated with a longer operative time.
Background
The most effective dosing strategy of meropenem for patients undergoing continuous renal replacement therapy (CRRT) remains uncertain. This study aimed to analyze the population pharmacokinetics (popPKs) of unbound meropenem and establish an appropriate dosing approach.
Methods
This prospective study involved 19 patients for the development of a popPK model and an additional 10 for its validation. Ethical approval was obtained.
Results
The clearance of unbound meropenem was influenced by the sequential organ failure assessment (SOFA) score [=2.22 × (SOFA score/12)^1.88] and the effluent flow rate from the CRRT device, with an interindividual variability of 44.5%. The volume of distribution was affected by the simplified acute physiology score II [=23.1 × (simplified acute physiology score II/52)^1.54]. Monte Carlo simulations suggested meropenem doses ranging from 1.0 to 3.0 g/d using continuous infusion to achieve a target time above the 4 times of minimum inhibitory concentration of the unbound form (% f T >4×MIC ) of 100% for definitive therapy. For empirical therapy, a dose of 1.0 g/d using continuous infusion was recommended to target % f T >MIC of 100%.
Conclusions
This study developed a popPK model for unbound meropenem in patients undergoing CRRT and formulated dosing guidelines.
Clinical trial registration
UMIN000024321.
Objectives: To investigate the relationship between sublingual microcirculation and the prognosis of sepsis. Data sources: The PubMed, Web of Science, Embase, and China National Knowledge Infrastructure (CNKI) databases were searched to identify studies published from January 2003 to November 2023. Study selection: Clinical studies examining sublingual microcirculation and the prognosis of sepsis were included. Data extraction: Sublingual microcirculation indices included the microvascular blood index (MFI), total vascular density (TVD), perfusion vascular density (PVD), perfusion vascular vessel (PPV), and heterogeneity index (HI). Prognostic outcomes included mortality and severity. Funnel plots and Egger's test were used to detect publication bias. The ability of the small vessel PPV (PPVs) to predict sepsis-related mortality was analyzed based on the summary receiver operating characteristic (SROC) curve, pooled sensitivity, and pooled specificity. Data synthesis: Twenty-five studies involving 1750 subjects were included. The TVD (95% CI 0.11-0.39), PVD (95% CI 0.42-0.88), PPV (95% CI 6.63-13.83), and MFI (95% CI 0.13-0.6) of the survival group were greater than those of the nonsurvival group. The HI in the survival group was lower than that in the nonsurvival group (95% CI −0.49 to −0.03). The TVD (95% CI 0.41-0.83), PVD (95% CI 0.83-1.17), PPV (95% CI 14.49-24.9), and MFI (95% CI 0.25-0.66) of the nonsevere group were greater than those of the severe group. Subgroup analysis revealed no significant difference in TVD between the survival group and the nonsurvival group in the small vessel subgroup. The area under the SROC curve (AUC) was 0.88. Conclusions: Sublingual microcirculation was worse among patients who died and patients with severe sepsis than among patients who survived and patients with nonsevere sepsis. PPV has a good predictive value for the mortality of sepsis patients. This study was recorded in PROSPERO (registration number: CRD42023486349).
Sepsis is a severe disease that occurs when the body's immune system reacts excessively to infection. The body's response, which includes an intense anti-bacterial reaction, can damage its tissues and organs. Neutrophils are the major components of white blood cells in circulation and play a vital role in innate immunity while fighting against infections, and are considered a feature determining sepsis classification. There's a plethora of basic research detailing neutrophil functioning, among which, the study of neutrophil extracellular traps (NETs) is providing novel insights into mechanisms and treatments of sepsis. This review explores their functions, dysfunctions, and influences in the context of sepsis. The interplay between neutrophils and the human microbiome and the impact of DNA methylation on neutrophil function in sepsis are crucial areas of study. The interaction between neutrophils and the human microbiome is complex, particularly in the context of sepsis where dysbiosis may occur. We highlight the importance of deciphering neutrophil’s functional alterations and their epigenetic features in sepsis because it is critical for defining sepsis endotypes and opening up the possibility for novel diagnostic methods and therapy. Specifically, epigenetic signatures are pivotal since they will provide a novel implication for sepsis diagnostic method when used in combination with the cell-free DNA (cfDNA). Research is exploring how specific patterns of DNA methylation in neutrophils, detectable in cfDNA, could serve as biomarkers for the early detection of sepsis.
Sepsis and septic shock are life-threatening conditions that are globally responsible for almost 20% of mortality, especially in low and middle-income countries. This review was conducted on PubMed and Google Scholar databases with keywords sepsis, septic shock, sepsis management, and sepsis complications. Articles published up to July 2023 in English were included. Diagnosis and management should be carried out without unnecessary delay. Cooperation between various medical specialties including intensive care doctors, neurologists, hepatologists, cardiologists, and pediatric doctors is needed if a child is affected. New strategies have to be implemented in low and middle-income countries to decrease the sepsis incidence and reduce mortality in the population.
Purpose
To evaluate the impact of severe acute kidney injury (AKI) on short-term mortality in patients with urosepsis.
Methods
This prospective cohort study evaluated 207 patients with urosepsis. AKI was diagnosed in accordance with the Kidney Disease Improving Global Outcomes criteria, and severe AKI was defined as stage 2 or 3 AKI. Patients were divided into two groups: patients who developed severe AKI (severe AKI group) and patients who did not (control group). The primary endpoint was all-cause mortality within 30 days. The secondary endpoints were 90-day mortality and in-hospital mortality. The exploratory outcomes were the risk factors for severe AKI development.
Results
The median patient age was 79 years. Of the 207 patients, 56 (27%) developed severe AKI. The 30-day mortality rate in the severe AKI group was significantly higher than that in the control group (20% vs. 2.0%, respectively; P < 0.001). In the multivariable analysis, performance status and severe AKI were significantly associated with 30-day mortality. The in-hospital mortality and 90-day mortality rates in the severe AKI group were significantly higher than those in the control group (P < 0.001 and P < 0.001, respectively). In the multivariable analysis, age, urolithiasis-related sepsis, lactate values, and disseminated intravascular coagulation were significantly associated with severe AKI development.
Conclusions
Severe AKI was a common complication in patients with urosepsis and contributed to high short-term mortality rates.
Background
Sepsis is a common syndrome of multiorgan system dysfunction secondary to the dysregulated inflammatory response to infection. The role of pancreatic stone protein (PSP) in diagnosing sepsis has been investigated in previous studies. The meta-analysis aimed to comprehensively investigate the diagnostic value of PSP in identifying sepsis.
Methods
PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI), were systematically searched. Studies investigating the diagnostic performance of PSP were included. Pooled sensitivity, specificity, positive Likelihood Ratio (+ LR) and negative Likelihood Ratio (-LR), diagnostic odds ratio (DOR), and area under the curve (AUC) of summary receiver operating characteristic (SROC) were calculated.
Results
The sensitivity of PSP was 0.88 (95% CI: 0.77–0.94), and the pooled specificity was 0.78 (95% CI: 0.65–0.87). Pooled + LR, -LR, and DOR were 4.1 (2.3, 7.3), 0.16 (0.07, 0.34), and 26 (7, 98). The AUC value for the SROC of PSP was 0.90 (0.87, 0.92). The pooled sensitivity, specificity, + LR and - LR, and DOR for PSP among neonates were 0.91 (95% CI: 0.84, 0.96), 0.66 (95% CI: 0.58, 0.74), 3.97 (95% CI: 0.53, 29.58), 0.13 (95% CI: 0.02, 1.00), and 31.27 (95% CI: 0.97, 1004.60).
Conclusions
This study indicates that PSP demonstrated favorable diagnostic accuracy in detecting sepsis. Well-designed studies are warranted to ascertain the value of PSP measurement to guide early empirical antibiotic treatment, particularly in neonates.
Objective
To investigate the protective effect and possible mechanisms of vitamin B6 against renal injury in patients with sepsis.
Methods
A total of 128 patients with sepsis who met the entry criteria in multiple centres were randomly divided into experimental (intravenous vitamin B6 therapy) and control (intravenous 0.9% sodium chloride therapy) groups based on usual care. Clinical data, the inflammatory response indicators interleukin 6 (IL-6), interleukin 8 (IL-8), tumour necrosis factor (TNF-α) and endothelin-1 (ET-1), the oxidative stress response indicators superoxide dismutase, glutathione and malondialdehyde, and renal function (assessed by blood urea nitrogen [BUN], serum creatinine [SCr] and renal resistance index [RRI] monitored by ultrasound) were compared between the two groups.
Results
After 7 d of treatment, the IL-6, IL-8, TNF-α and ET-1 levels in the experimental group were significantly lower than those in the control group, the oxidative stress response indicators were significantly improved in the experimental group and the BUN, SCr and RRI values in the experimental group were significantly lower than those in the control group ( p < 0.05). There was no statistical difference between the two groups in the rate of renal replacement therapy and 28 d mortality ( p > 0.05). However, the ICU length of stay and the total hospitalisation expenses in the experimental group were significantly lower than those in the control group ( p < 0.05).
Conclusion
The administration of vitamin B6 in the treatment of patients with sepsis attenuates renal injury, and the mechanism may be related to pyridoxine decreasing the levels of inflammatory mediators and their regulation by redox stress.
Clinical trial registration: ClinicalTrials.gov Identifier: NCT06008223
Background: The mortality rate of afebrile bacteremia has been reported to be as high as 45%. This investigation focused on the risk factors and predictive performance of scoring systems for the clinical outcomes of afebrile patients with monomicrobial gram-negative bacteria (GNB) in the emergency department (ED). Methods: We conducted a retrospective analysis of afebrile adult ED patients with monomicrobial GNB bacteremia from January 2012 to December 2021. We dissected the demographics, clinical pictures, and laboratory investigations. We applied five scoring systems and three revised systems to predict the clinical outcomes. Results: There were 600 patients included (358 males and 242 females), with a mean age of 69.6 ± 15.4 years. The overall mortality rate was 50.17%, reaching 68.52% (74/108) in cirrhotic patients. Escherichia coli was the leading pathogen (42.83%). The non-survivors had higher scores of the original MEDS (p < 0.001), NEWS (p < 0.001), MEWS (p < 0.001), qSOFA (p < 0.001), and REMS (p = 0.030). In univariate logistic regression analyses, several risk factors had a higher odds ratio (OR) for mortality, including liver cirrhosis (OR 2.541, p < 0.001), malignancy (OR 2.259, p < 0.001), septic shock (OR 2.077, p = 0.002), and male gender (OR 0.535, p < 0.001). The MEDS demonstrated that the best predictive power with the maximum area under the curve (AUC) was measured at 0.773 at the cut-off point of 11. The AUCs of the original NEWS, MEWS, qSOFA, and REMS were 0.663, 0.584, 0.572, and 0.553, respectively. We revised the original MEDS, NEWS, and qSOFA by adding red cell distribution width, albumin, and lactate scores and found a better predictive power of the AUC of 0.797, 0.719, and 0.694 on the revised MEDS ≥11, revised qSOFA ≥ 3, and revised NEWS ≥ 6, respectively. Conclusions: The original MEDS, revised MEDS, revised qSOFA, and revised NEWS were valuable tools for predicting the mortality risk in afebrile patients with monomicrobial GNB bacteremia. We suggested that clinicians should explore patients with the risk factors mentioned above for possible severe infection, even in the absence of fever and initiate hemodynamic support and early adequate antibiotic therapy in patients with higher scores of the original MEDS (≥11), revised MEDS (≥11), revised NEWS (≥6), and revised qSOFA (≥3).
Acute pancreatitis (AP) is a common disease with no targeted therapy and has varied outcomes ranging from spontaneous resolution to being lethal. While typically painful, AP can also be painless. Various agents, including opioids are used for pain control in AP; the risks, and benefits of which are often debated. Since experimental AP in mice is used to study the efficacy of potential therapies, we studied the effect of a commonly used opioid buprenorphine on the initiation and progression of AP. For this we administered extended-release buprenorphine subcutaneously prior to inducing the previously established severe AP model that uses Interleukins 12 and 18 (IL12,18) in genetically obese (ob/ob) mice and compared this to mice with AP but without the drug. Mice were monitored over 3 days and parameters of AP induction and progression were compared. Buprenorphine significantly reduced the serum amylase, lipase, pancreatic necrosis, and AP associated fat necrosis which is ubiquitous in obese mice and humans. Buprenorphine delayed the AP associated reduction of carotid artery pulse distention, and development of hypothermia, hastened renal injury, and muted the early increase in respiratory rate vs. IL12,18 alone. The site of buprenorphine injection appeared erythematous, inflamed, and microscopically showed thinning, loss of epidermal layers which had increased apoptosis. In summary, subcutaneous extended-release buprenorphine interfered with the induction of AP by reducing serum amylase, lipase, pancreatic and fat necrosis, the worsening of AP by delaying hypotension, hypothermia, while hastening renal injury, respiratory depression, and causing cutaneous injury at the site of injection.
Background
Sepsis syndromes are a major burden in the ICU with very high mortality. Vasopressin and copeptin are released in response to hypovolemia and have shown potential significance in diagnosing sepsis.
Objective
To investigate the levels of copeptin in patients with sepsis syndromes and evaluate its relation with patient prognosis and mortality.
Methods
Four databases were searched for literature published from inception to the 8th of November 2022. Original research articles where copeptin was measured in sepsis patients and compared with controls were included. Data extraction and synthesis: study characteristics, levels of copeptin in the participants, and copeptin assay description were extracted. Levels of copeptin in patients were pooled and compared with controls in terms of the standard mean difference (SMD) generated using a random-effects model.
Results
Fifteen studies met the selection criteria. Copeptin levels were significantly higher in patients with sepsis, severe sepsis, and septic shock as compared to controls [(SMD: 1.49, 95% CI: 0.81–2.16, P <0.0001), (SMD: 1.94, 95% CI: 0.34–3.54, P =0.02), and (SMD: 2.17, 95% CI: 0.68–3.66, P =0.004), respectively]. The highest copeptin levels were noted in septic shock patients. The admission copeptin levels were significantly lower in survivors as compared to nonsurvivors (SMD: −1.73; 95% CI: −2.41 to −1.06, P <0.001).
Conclusion and Relevance
Copeptin was significantly elevated in sepsis, severe sepsis, and septic shock. Survivors had a significantly lower copeptin during admission. Copeptin offered an excellent predictability to predict 1-month mortality. Measuring the copeptin in sepsis patients can aid treating physicians to foresee patients’ prognosis.
Background
Cardiovascular implantable electronic device (CIED) infections are a common indication for device extraction. Early diagnosis and complete system removal are crucial to reduce morbidity and mortality. The lack of clear infectious symptoms makes the diagnosis of pocket infections challenging and may delay referral for extraction.
Objective
We aimed to determine if inflammatory biomarkers can help diagnose CIED isolated pocket infection.
Methods
We performed a retrospective analysis of all patients undergoing transvenous lead extraction for CIED infection at the University of California San Diego from 2012 to 2022 (N = 156). Patients were classified as systemic infection (n = 88) or isolated pocket infection (n = 68). Prospectively collected preoperative procalcitonin (PCT), C-reactive protein, and white blood cell count were compared between groups.
Results
Pairwise comparisons revealed that the systemic infection group had a higher PCT than the control group (P < .001) and the pocket infection group (P = .009). However, there was no significant difference in PCT value between control subjects and isolated pocket infection subjects. Higher white blood cell count was only associated with systemic infection when compared with our control group (P = .018).
Conclusion
In patients diagnosed with CIED infections requiring extraction, inflammatory biomarkers were not elevated in isolated pocket infection. Inflammatory markers are not predictive of the diagnosis of pocket infections, which ultimately requires a high level of clinical suspicion.
Rhodotorula is a genus of ubiquitous pigmented yeast found in the environment and as a commensal of human and animal microbiota. Previously considered nonpathogenic, Rhodotorula has emerged as an important cause of nosocomial and opportunistic infections in susceptible patients. While Rhodotorula spp. are common commensals in healthy individuals, the yeast may overgrow in patients with compromised immune systems causing disease. Herein, we provide a detailed presentation of a rare case involving a 79-year-old Caucasian female with a lung malignancy who developed massive cavitations in her lungs. The patient's lung tissue was cultured and grew an unidentified species of the genus Rhodotorula. The patient's health declined rapidly, and she expired due to hypoxemia. Clinicians must recognize patient groups potentially at risk for infection with Rhodotorula spp. Early identification and initiation of appropriate interventions are crucial in reducing mortality associated with this opportunistic fungal infection.
Machine learning based early identification of sepsis in the Emergency department remains a challenging problem, primarily due to the lack of a gold standard for sepsis diagnosis and the corresponding labels required as part of training. In this work, we present a deep learning based predictive model to enable early identification of patients at risk of developing sepsis based on data from the first 24 hours of admission. The predictive model is based on the existing routine blood test results commonly performed on patients CBC (Complete Blood Count), CMP (Comprehensive Metabolic Panel), and Lipid panel, together with vitals, age and sex. To address the challenge of label uncertainty as a part of training process, we explore two different definitions, namely, Sepsis-3 and Adult Sepsis Event and analyze the advantages and drawbacks of each in the context of patient clinical parameters and comorbidities. We particularly analyze the influence of the ground truth label quality on the performance of the overall deep learning system. We see that the model is able to identify patients in the first 24 hours with 83.7% sensitivity and 80% specificity. Our findings underscore the limitations of using individual labels for sepsis and emphasize the superiority of ensemble classifiers based on multiple heterogeneous labels, in the identification of patients with sepsis. The variable performance of the model across different sub-cohorts with specific clinical conditions underscores the need for tailored approaches in sepsis diagnosis, particularly when dealing with patients with confounding comorbidities.
Paroxysmal sympathetic hyperactivity (PSH) is a clinical syndrome associated with many types of acquired brain injuries characterized by episodic uncontrolled physiologic surges of sympathetic activity. It features varying combinations and degrees of hyperthermia, diaphoresis, tachycardia, hypertension, tachypnea, and dystonic posturing. This constellation of symptomatology has been acknowledged in acquired brain injury for decades, but due to confusing nomenclature and inconsistent clinical definitions, its recognition and treatment as a syndrome have only recently begun to become more standardized. At this time PSH remains a diagnosis of exclusion, but one with which clinicians in the acute care setting should be familiar since its development is associated with longer hospital stays, higher rates of complications, and increased costs of care. Furthermore, delayed recognition and treatment can result in higher morbidity and worse outcomes.
Invasive bacterial infections and sepsis are persistent global health concerns, complicated further by the escalating threat of antibiotic resistance. Over the past 40 years, collaborative endeavors to improve the diagnosis and critical care of septic patients have improved outcomes, yet grappling with the intricate immune dysfunction underlying the septic condition remains a formidable challenge. Anti-inflammatory interventions that exhibited promise in murine models failed to manifest consistent survival benefits in clinical studies through recent decades. Novel therapeutic approaches that target bacterial virulence factors, for example with monoclonal antibodies, aim to thwart pathogen-driven damage and restore an advantage to the immune system. A pioneering technology addressing this challenge is biomimetic nanoparticles-a therapeutic platform featuring nanoscale particles enveloped in natural cell membranes. Borne from the quest for a durable drug delivery system, the original red blood cell-coated nanoparticles showcased a broad capacity to absorb bacterial and environmental toxins from serum. Tailoring the membrane coating to immune cell sources imparts unique characteristics to the nanoparticles suitable for broader application in infectious disease. Their capacity to bind both inflammatory signals and virulence factors assembles the most promising sepsis therapies into a singular, pathogen-agnostic therapeutic. This review explores the ongoing work on immune cell-coated nanoparticle therapeutics for infection and sepsis. Significance Statement In the quest to combat antibiotic-resistant bacterial infections and sepsis, an innovative approach has emerged in which nanoscale particles are enveloped in natural cell membranes purified from human blood cells. Since this technology shows the ability to (a) neutralize bacterial toxins that injure host cells and (b) quell the exaggerated septic inflammation that leads to deadly organ system failure, these novel nanomedicines may represent a versatile strategy to complement antibiotics and vaccines in the ongoing battle against infectious diseases.
Introduction: The utility of serial scoring systems in identifying distinct sepsis phenotypes remains unknown. Methods: Eligible adults were classified into culture-positive (Cx+) and culture-negative (Cx-) groups alongside pre-defined culture subgroups. Average SIRS & SEP (novel scoring system) scores were calculated at t = 0 and hours 3,6,12 & 24 before and after t = 0. The primary outcome was a difference in SIRS/SEP scores amongst those that were Cx+ or Cx- at any time point. Secondary outcomes were comparing total and component SIRS/SEP scores in microbiologic subgroups over serial time points. Results: 4,701 Cx+ and 3254 Cx- patients met eligibility criteria. Statistically significant differences were seen in the average SIRS score between Cx + and Cx- groups at hours six (Cx+ 1.40+1.04 vs Cx- 1.35+1.01) & 12 (Cx+ 0.95+0.95 vs Cx- 0.90+0.90) after t = 0. The hematologic, urologic, and neurologic subgroups had significant differences at numerous time points before and after T = 0. Similar findings were observed with the SEP scores. Cx+ and Cx- groups (including subgroups) consistently doubled both SIRS/SEP scores before t = 0 with an eventual return to baseline values after T = 0 but at different gradients. Conclusion: Significant differences in SIRS/SEP scores were seen in Cx+ & Cx- patients at sequential time points. This microbiologic approach in homogenous culture cohorts has the potential to identify distinct phenotypes of sepsis efficiently and practically. Consistent increases in SIRS/SEP scores before t = 0 and sequential decreases after t = 0 may allow for early detection, intervention, and provision for real-time monitoring of therapeutic responses in patients with concerns for sepsis.
The objective of this study was to refine the APACHE (Acute Physiology, Age, Chronic Health Evaluation) methodology in order to more accurately predict hospital mortality risk for critically ill hospitalized adults. We prospectively collected data on 17,440 unselected adult medical/surgical intensive care unit (ICU) admissions at 40 US hospitals (14 volunteer tertiary-care institutions and 26 hospitals randomly chosen to represent intensive care services nationwide). We analyzed the relationship between the patient's likelihood of surviving to hospital discharge and the following predictive variables: major medical and surgical disease categories, acute physiologic abnormalities, age, preexisting functional limitations, major comorbidities, and treatment location immediately prior to ICU admission. The APACHE III prognostic system consists of two options: (1) an APACHE III score, which can provide initial risk stratification for severely ill hospitalized patients within independently defined patient groups; and (2) an APACHE III predictive equation, which uses APACHE III score and reference data on major disease categories and treatment location immediately prior to ICU admission to provide risk estimates for hospital mortality for individual ICU patients. A five-point increase in APACHE III score (range, 0 to 299) is independently associated with a statistically significant increase in the relative risk of hospital death (odds ratio, 1.10 to 1.78) within each of 78 major medical and surgical disease categories. The overall predictive accuracy of the first-day APACHE III equation was such that, within 24 h of ICU admission, 95 percent of ICU admissions could be given a risk estimate for hospital death that was within 3 percent of that actually observed (r2 = 0.41; receiver operating characteristic = 0.90). Recording changes in the APACHE III score on each subsequent day of ICU therapy provided daily updates in these risk estimates. When applied across the individual ICUs, the first-day APACHE III equation accounted for the majority of variation in observed death rates (r2 = 0.90, p less than 0.0001).
Septic shock is the commonest cause of death in intensive care units. Although sepsis usually produces a low systemic vascular resistance and elevated cardiac output, strong evidence (decreased ejection fraction and reduced response to fluid administration) suggests that the ventricular myocardium is depressed and the ventricle dilated. In survivors, these abnormalities are reversible. Failure to develop ventricular dilatation in nonsurvivors suggests that dilatation is a compensatory mechanism needed to maintain adequate cardiac output. With a canine model of septic shock that is very similar to human sepsis, myocardial depression was confirmed using load-independent measures of ventricular performance. Endotoxin administration to humans simulates the qualitative, cardiovascular abnormalities of sepsis. The pathogenesis of septic shock is extraordinarily complex. Diverse microorganisms can generate toxins, stimulating release of potent mediators that act on vasculature and myocardium. A circulating myocardial depressant substance has been closely associated with the myocardial depression of human septic shock. Therapy has emphasized early use of antibiotics, critical care monitoring, aggressive volume resuscitation, and, if shock continues, use of inotropic agents and vasopressors. Pharmacologic or immunologic antagonism of endotoxin or other mediators may prove to enhance survival in this highly lethal syndrome.
In addition to activating T and B lymphocytes, interleukin 1 (IL-1) induces several hematologic and metabolic changes typical of host responses to infection and injury. We now report a new biological property, namely, the induction of hypotension. Rabbits given a single intravenous injection of recombinant human IL-1-beta (5 micrograms/kg) rapidly developed decreased systemic arterial pressure, which reached the lowest levels after 50-60 min and slowly returned to pre-IL-1 values after 3 h. Associated with the hypotension, systemic vascular resistance and central venous pressure fell, while cardiac output and heart rate increased. These responses were prevented by ibuprofen given 15 min before the IL-1. A bolus injection of IL-1 followed by a 2-h infusion sustained the hypotension and was associated with leukopenia and thrombocytopenia. Ibuprofen given at the mid-point of the infusion reversed the changes in all hemodynamic parameters, but had no effect on the leukopenia or thrombocytopenia. Tumor necrosis factor (TNF) also induced a shock-like state in rabbits. When the dose of IL-1 or TNF was reduced to 1 microgram/kg, no hemodynamic changes were observed; however, the combination of these low doses of both cytokines resulted in a profound shock-like state including histological evidence of severe pulmonary edema and hemorrhage. Pretreatment with ibuprofen prevented the hemodynamic, leukocyte, and platelet changes induced by the low-dose cytokine combination, and ameliorated the pulmonary tissue damage. These results demonstrate that IL-1, like TNF, possesses the ability to induce hemodynamic and hematological changes typical of septic shock, and that the combination of IL-1 and TNF is more potent than either agent alone. These effects seem to require cyclooxygenase products, and suggest that intravenous cyclooxygenase inhibitors may be of therapeutic value in patients with IL-1/TNF-mediated shock.
Bacterial infection of the mammalian bloodstream can lead to overwhelming sepsis, a potentially fatal syndrome of irreversible cardiovascular collapse (shock) and critical organ failure. Cachectin, also known as tumour necrosis factor, is a macrophage-derived peptide hormone released in response to bacterial lipopolysaccharide, and it has been implicated as a principal mediator of endotoxic shock, although its function in bacterial sepsis is not known. Anaesthetized baboons were passively immunized against endogenous cachectin and subsequently infused with an LD100 dose of live Escherichia coli. Control animals (not immunized against cachectin) developed hypotension followed by lethal renal and pulmonary failure. Neutralizing monoclonal anti-cachectin antibody fragments (F(ab')2) administered to baboons only one hour before bacterial challenge protected against shock, but did not prevent critical organ failure. Complete protection against shock, vital organ dysfunction, persistent stress hormone release and death was conferred by administration of antibodies 2 h before bacterial infusion. These results indicate that cachectin is a mediator of fatal bacteraemic shock, and suggest that antibodies against cachectin offer a potential therapy of life-threatening infection.
Objective
To evaluate the current definitions for sepsis and clarify and quantify the risk for intensive care unit (ICU) patients with sepsis.
Design
A prospective cohort analysis of 519 patients with a primary clinical diagnosis of sepsis treated in the ICUs of 40 US hospitals drawn from a nationally representative sample of 17,440 admissions.
Measurements
Patient's age, treatment location prior to ICU admission, comorbidities, origin of sepsis, daily physiologic measurements, therapeutic intensity, and subsequent hospital mortality rate.
Intervention
Patients were categorized into subgroups by important risk factors and into current clinical definitions of sepsis. Patients also were provided an individual risk of hospital mortality based on their individual predicted risk by using the first ICU day APACHE III score, treatment location prior to ICU admission, and etiology of sepsis.
Results
Patients with a designated urinary source of sepsis had a significantly lower baseline risk of death (30 percent) than patients with other causes (54 percent, p<0.01). Patients admitted to the ICU from the emergency department also had significantly lower mortality (37 percent) than patients admitted from hospital wards, other units within the hospital, or transferred from other hospitals (55 percent, p<0.01). Recognized definitions such as “sepsis syndrome” and “septic shock” identified groups of patients with significantly different mortality rates, 40 percent and 64 percent, respectively (p<0.01), but the range of individual patient risks within these groups were indistinguishable from the 211 patients (41 percent) that did not meet these definitions during the initial seven days of ICU treatment. Multivariate analysis using initial APACHE HI score, etiology (urosepsis or other), and treatment location prior to ICU admission provided the greatest degree of discrimination (ROC = 0.82) of patients by risk of hospital death. Conclusions: Sepsis is a complex clinical entity and could be viewed as a continuum with substantial variation in initial severity and risk of hospital death. One accurate description of sepsis is the continuous measure of hospital mortality risk estimated primarily from physiologic abnormalities.
Patients with the adult respiratory distress syndrome and multiple organ system failure have a high mortality rate despite extensive supportive therapy. We evaluated the role of multiple organ system failure and infection in 37 consecutive survivors of the syndrome, and 47 consecutive nonsurvivors on whom autopsies were done. Failure of the central nervous, coagulation, endocrine, gastrointestinal, and renal systems was common in all patients but was more frequent in those who died. Major infections occurred in 46 nonsurvivors and 22 survivors. All patients with bacteremia who had a clinically identified site of infection survived, whereas all patients with bacteremia without a clinically identified site of infection died. Autopsy results of the latter group showed infections requiring surgical drainage for complete therapy. Patients clinically septic but without bacteremia and without a clear site of infection were shown at autopsy to have pneumonia. Multiple organ system failure was more common in infected (93%) than noninfected (47%) patients. Vigorous evaluation and treatment of infection in patients with the adult respiratory distress syndrome may improve survival.
Objective.
—To assess the efficacy of adjunctive monoclonal antibody antiendotoxin immunotherapy in patients with gram-negative sepsis.Design.
—Double-blind, randomized, placebo-controlled trial.Setting.
—Thirty-three university-affiliated centers, including Veterans Affairs, community, and municipal hospitals.Patients.
—Hospitalized adults with signs of gram-negative infection and a systemic septic response.Intervention.
—Patients were assigned to receive either 2 mg/kg of a murine monoclonal antibody directed against gram-negative endotoxin (E5) or placebo. A second infusion was administered 24 hours later.Main Outcome Measures.
—Mortality over the 30-day study period, resolution of organ failures, and safety.Results.
—Four hundred eighty-six patients were enrolled. Three hundred sixteen had confirmed gram-negative sepsis (54% bacteremic, 46% nonbacteremic). The survival difference was not statistically significant for all patients. Among patients with gram-negative sepsis who were not in shock at study entry (n = 137), E5 treatment resulted in significantly greater survival (relative risk, 2.3; P =.01). Resolution of individual organ failures was more frequent among these patients, occurring in 19 (54%) of 35 patients in the E5 group vs eight (30%) of 27 in the placebo group (P =.05). Four reversible allergic reactions occurred among 247 patients (1.6%) receiving E5. No other toxicity was identified.Conclusions.
—Treatment with E5 antiendotoxin antibody appears safe. It reduces mortality and enhances the resolution of organ failure among patients with gram-negative sepsis who are not in shock when treated.(JAMA. 1991;266:1097-1102)
A response surface for critically ill patients is described. The coordinates of the three-dimensional response surface are two control variables, or state variables, related to aerobic and anaerobic metabolism, and a response variable, the A-VO2 difference. The data conform to a cusp catastrophe manifold. Cardiac insufficiency, adaptive response to stress, and sepsis may be distinguished by this model. The distinction between control and response variables is discussed.
As the care of injured patients has evolved and improved, various organ systems have in turn been the limiting factor affecting recovery after a severe injury or major operation. Although patients after operation or injury may die from a number of specific or general injuries and complications, there has usually been, at any one time in surgical history, a particular organ system that has been the most common and difficult problem. The major wars have provided larger experience and more concentrated documentation of what was happening simultaneously in civilian hospitals to patients traumatized by injury or operation. In the 1930s and during the early part of World War II, the major organ system that limited survival after injury was the cardiovascular apparatus (shock), even when that system was previously normal. An understanding of blood loss, the requirements of whole blood replacement for hypovolemia, and the nature of traumatic or wound
Sepsis, an important cause of hospital mortality, continues to be a diagnostic and therapeutic challenge. To define more clearly the impact of encephalopathy on the course of sepsis, the various clinical signs of sepsis, blood culture results, and mortality rates were examined in relation to mental status in septic patients. Patients were classified as having an acutely altered mental status due to sepsis (AAMS), preexisting altered mental status (PAMS), or normal mental status (NMS). Twenty-three (307/1333) percent of the study patients had an acutely altered sensorium secondary to sepsis. Patients with AAMS had a higher mortality (49%) than patients with PAMS (41%) or patients with NMS (26%) (p < .000001). Multivariate analysis disclosed that altered mental status, hypothermia, hypotension, thrombocytopenia, and the absence of shaking chills were independent predictors of increased mortality in the sepsis syndrome. Patients with Gram-negative bacteremia (28%) were as likely to have AAMS as patients with Gram-positive bacteremia (25%) or patients with negative blood cultures (23%). In summary, alterations in mental status are common in septic patients, and are associated with significantly higher mortality.
(C) Williams & Wilkins 1990. All Rights Reserved.
Forty-two postoperative patients, each with demonstrable failure of two or more vital organ systems, have been studied as they define a syndrome of multiple organ failure. They typify the emerging clinical entity of patients kept alive solely by reason of specific mechanical and pharmacologic support. Trauma initiated hospitalization in 40 per cent and major bleeding, in 11 per cent. Sepsis was judged to be of etiologic significance in 69 per cent. Complications in clinical management were, in retrospect, thought to be of contributory etiologic significance in 57 per cent. Twenty-nine of 42 patients died; a mortality of 69 per cent. Mean duration of multiple organ failure was 30.5 days. Hospital cost, omitting the physician's fees, was conservatively estimated at $700 per day. Scientific, social, moral, ethical and legal factors emphasize the need to establish a statistically valid large data base concerning this new man-made syndrome which has both important scientific and social implications. This study is a first step in this direction.
Remote or local infection appears to be causally associated with major organ failure in some surgical patients. Experience with the patients described suggests that the converse relationship may be clinically useful: organ failure may indicate the presence of otherwise occult intra-abdominal infection in postoperative patients and trauma victims. Support of organ function without definitive correction of underlying infection is only pallative.
Modern life-sustaining therapy often succeeds in postponing death but may be ineffective at restoring health. Decisions that
influence the time and circumstances of an individual's death are now common and require an accurate and comprehensive characterization
of likely outcome. Evaluation of alternative outcomes requires acknowledgement that most patients find some outcomes to be
worse than death. Improved understanding of major predictors of patient outcome, combined with rapidly expanding technical
abilities to collect and manipulate large amounts of detailed clinical data, have created a new intellectual and technical
basis for estimating outcomes from intensive medical care. Such objective probability estimates, such as the system described
here, can reduce uncertainty about difficult clinical decisions and can be used by physicians, patients, and society to reorient
health care toward more scientifically and ethically defensible approaches.
The terms bacteremia, sepsis, septicemia, sepsis syndrome, and septic shock are used in various contexts. Because imprecise meanings are often misinterpreted, standardized terminology is advocated. Positive blood culture constitutes the diagnostic criterion for bacteremia. The term septicemia should be discarded. Sepsis should be defined as clinical evidence of infection plus the systemic response to it (tachypnea, tachycardia, and hypothermia or hyperthermia). The sepsis syndrome is sepsis with evidence of altered organ perfusion. Septic shock and refractory septic shock are defined as the sepsis syndrome with responsive and refractory hypotension, respectively. Early recognition of sepsis may improve survival through prompt and aggressive therapeutic intervention.
HA-1A is a human monoclonal IgM antibody that binds specifically to the lipid A domain of endotoxin and prevents death in laboratory animals with gram-negative bacteremia and endotoxemia.
To evaluate the efficacy and safety of HA-1A, we conducted a randomized, double-blind trial in patients with sepsis and a presumed diagnosis of gram-negative infection. The patients received either a single 100-mg intravenous dose of HA-1A (in 3.5 g of albumin) or placebo (3.5 g of albumin). Other interventions, including the administration of antibiotics and fluids, were not affected by the study protocol.
Of 543 patients with sepsis who were treated, 200 (37 percent) had gram-negative bacteremia as proved by blood culture. For the patients with gram-negative bacteremia followed to death or day 28, there were 45 deaths among the 92 recipients of placebo (49 percent) and 32 deaths among the 105 recipients of HA-1A (30 percent; P = 0.014). For the patients with gram-negative bacteremia and shock at entry, there were 27 deaths among the 47 recipients of placebo (57 percent) and 18 deaths among the 54 recipients of HA-1A (33 percent; P = 0.017). Analyses that stratified according to the severity of illness at entry showed improved survival with HA-1A treatment in both severely ill and less severely ill patients. Of the 196 patients with gram-negative bacteremia who were followed to hospital discharge or death, 45 of the 93 given placebo (48 percent) were discharged alive, as compared with 65 of the 103 treated with HA-1A (63 percent; P = 0.038). No benefit of treatment with HA-1A was demonstrated in the 343 patients with sepsis who did not prove to have gram-negative bacteremia. For all 543 patients with sepsis who were treated, the mortality rate was 43 percent among the recipients of placebo and 39 percent among those given HA-1A (P = 0.24). All patients tolerated HA-1A well, and no anti-HA-1A antibodies were detected.
HA-1A is safe and effective for the treatment of patients with sepsis and gram-negative bacteremia.
This paper describes work to develop a model-based system to support clinical decision-making. In previous articles, we have developed (from 695 measurement sets obtained from 148 patients) a physiologic state classification based on a set of 11 cardiovascular and metabolic measurements. There is an R or reference state, for stable ICU patients. Patients under (operative, traumatic, or compensated septic) stress, or with (septic or hepatic) metabolic, respiratory, or cardiac insufficiency are in the A, B, C or D states, respectively. We wished to make the state easier to measure and eventually available continuously, automatically, and noninvasively, as well as reflecting a wider group of bodily systems. The 5 centers define a 4 dimensional affine subspace, designated thecardiovascular state space. Using eigenvector analysis, we have found four new derived physiologic variables CV1, CV2, CV3 and CV4 that span the state space. We have fit sets of linear regression equations that allow the patient's position in the state space, and therefore his state, to be determined from more easily obtainable sets of measurements.
Further, we selected 1966 measurement sets from 512 patients at two hospitals. We used the data from 250 of these patients to define 13 prototypical types, namely survivors and deaths from various combinations of sepsis, cardiogenic decompensation, cirrhosis, and pneumonitis, following trauma or general surgery. For any future patient, the statistical theory of Bayesian inference allows one to infer back from the measurements observed to the probability of his being of any of these types and of surviving or dying. We used this method to predict the outcome of the other 262 patients, prospectively. Statistically, the predictions of survival or death were not significantly different from the actual. For individual patients, the method predicts a clinical course that closely follows the actual episodes in their history.
These results confirm and explain the validity of the concept of the patient state and make the state easier to compute. The patient state and the probability plot together help to stage, select, and evaluate therapy. They do not replace the clinician's judgement, but rather are tools that help the clinician to exercise judgement.
The production and consequences of the components of the state defined as 'clinically significant sepsis', as seen in patients undergoing intensive therapy--fever, shock, respiratory failure and multiple system failure--are complex. The syndrome is not necessarily accompanied by detectable bacteraemia; the effective management cannot wait upon positive blood cultures. Possibilities for more effective intervention include the use of monoclonal antibodies to endotoxin or to tumour necrosis factor, and of prostaglandins to alter the microcirculation. More refined definition of the severe sepsis syndrome will be required before these measures can be fully evaluated.
Systemic sepsis, including that originating from primary pneumonia, is the most common cause of the adult respiratory distress syndrome. Sepsis may initiate multiple system organ failure, with lung injury the first manifestation, because of the activation of inflammatory mediators such as interleukin-1 and tumor necrosis factor by bacterial cell walls. Once lung injury is established, nosocomial pneumonia, the most frequent and most potentially fatal infectious complication, may ensue. Prevention of this secondary infection, which can propagate established multi-organ failure, may follow from an understanding of its pathogenesis and is much needed because of the current limitations in the diagnosis and treatment of pneumonia associated with acute lung injury.
The differential roles of infection as a microbial phenomenon and sepsis as a host response were studied in 210 critically ill surgical patients. Infections occurred in 41.4% of all cases and in 82% of nonsurviving patients. Both infection and the expression of a septic response, measured as a sepsis score, were associated with significantly increased intensive care unit morbidity and mortality. Nonsurviving patients with infection had significantly higher sepsis scores than did survivors. Nonsurvivors with sepsis, on the other hand, did not differ from survivors with respect to any variable reflecting infection but did have higher mean sepsis scores. Maximum sepsis scores and sepsis scores on the day of death were similar in patients dying without infection and those dying with uncontrolled infection. The magnitude of the host septic response, independent of the presence, bacteriologic characteristics, or control of infection, is an important determinant of outcome in critical surgical illness.
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.
The potential role of platelet-activating factor (PAF) as a mediator of gastrointestinal ulceration associated with septic shock was examined in the rat. The damaging effects of both PAF and Escherichia coli endotoxin in the stomach and small intestine were compared, as were their effects on plasma leakage into the lumen of the gastrointestinal tract. Intravenous administration of either endotoxin or PAF produced extensive necrosis and vascular congestion in the stomach and small intestine, but not the distal colon. With either agent, the duodenum and jejunum were the tissues most susceptible to damage and in which the greatest plasma leakage was observed. The prolonged hypotension and gastrointestinal damage induced by PAF or endotoxin were significantly inhibited by three structurally dissimilar PAF antagonists (CV-3988, BN-52021, and Ro-193704). CV-3988 (10 mg/kg) significantly (p less than 0.05) reduced both endotoxin- and PAF-induced plasma leakage in the stomach and small intestine. Of the three antagonists, only CV-3988 significantly reduced ethanol-induced gastric mucosal damage, perhaps reflecting actions of this compound unrelated to antagonism of PAF receptors. These studies support the hypothesis that PAF is an important mediator of the hypotension and plasma leakage observed during endotoxic shock and its endogenous release may contribute to the gastrointestinal ulceration associated with this syndrome. Thus, PAF receptor antagonists may be useful for prevention of such ulceration.
The use of high-dose corticosteroids in the treatment of severe sepsis and septic shock remains controversial. Our study was designed as a prospective, randomized, double-blind, placebo-controlled trial of high-dose methylprednisolone sodium succinate for severe sepsis and septic shock. Diagnosis was based on the clinical suspicion of infection plus the presence of fever or hypothermia (rectal temperature greater than 38.3 degrees C [101 degrees F] or less than 35.6 degrees C [96 degrees F]), tachypnea (greater than 20 breaths per minute), tachycardia (greater than 90 beats per minute), and the presence of one of the following indications of organ dysfunction: a change in mental status, hypoxemia, elevated lactate levels, or oliguria. Three hundred eighty-two patients were enrolled. Treatment--either methylprednisolone sodium succinate (30 mg per kilogram of body weight) or placebo--was given in four infusions, starting within two hours of diagnosis. No significant differences were found in the prevention of shock, the reversal of shock, or overall mortality. In the subgroup of patients with elevated serum creatinine levels (greater than 2 mg per deciliter) at enrollment, mortality at 14 days was significantly increased among those receiving methylprednisolone (46 of 78 [59 percent] vs. 17 of 58 [29 percent] among those receiving placebo; P less than 0.01). Among patients treated with methylprednisolone, significantly more deaths were related to secondary infection. We conclude that the use of high-dose corticosteroids provides no benefit in the treatment of severe sepsis and septic shock.
The microbiology of infection acquired in the intensive care unit (ICU) was studied prospectively in 205 consecutive patients admitted to a surgical intensive care unit. A multiple organ failure (MOF) score was calculated for each admission. Susceptibility to ICU-acquired infection increased with increasing MOF scores. While Escherichia coli, Bacteroides fragilis, and enterococci were the most common isolates from infections present at the time of ICU admission, Staphylococcus epidermidis, Candida, and Pseudomonas dominated infections occurring in patients with high MOF scores. Mortality correlated highly with infection due to S epidermidis or Candida and only poorly with infection due to Pseudomonas or E coli; significant foci of invasive infection were frequently absent at autopsy. Quantitative cultures of proximal gastrointestinal fluid in 16 of these patients showed Candida, S epidermidis, and Pseudomonas to be the most common isolates, and all but one patient colonized with these organisms had invasive infection with the same organism. The proximal gastrointestinal tract appears to be an important occult reservoir of the predominant pathogens in MOF.
The hypermetabolism organ failure complex remains the predominant reason for both prolonged stay and death in the surgical intensive care unit. What was perceived as isolated organ failure, such as adult respiratory distress syndrome, is now seen as part of the systemic response to injury and repair. Sepsis has become the systemic inflammatory response due to invading microorganisms. What was once perceived as diagnostic of sepsis has been recognized after severe perfusion deficits and in the presence of continuing sources of dead and injured tissue. The transition to organ failure is usually a distinct clinical event and probably represents the onset of clinical hepatic failure. Once present, the organ failure syndrome has a high mortality rate. From a treatment perspective, it is recognized that there is probably no "magic bullet"; that regimens will probably be time dependent and "multiple drug"; and that the best treatment is prevention. Malnutrition, as opposed to changes in body composition that occur as a result of disease process, has become a recognized cofactor in morbidity and death in patients with persistent hypermetabolism and organ failure. The metabolic processes of hypermetabolism have become increasingly categorized and understood. The result has been the development of metabolic support principles that are distinct from those of nutritional support and are designed to prevent the end-organ changes of malnutrition and the development of substrate-limited metabolism, to support organ structure and function, and to attempt to arrest the metabolic processes. The initial problem was to learn to do no harm, an outcome reasonably achieved. In addition, several beneficial results have been recognized including new techniques to better support total body protein synthesis, hepatic protein synthesis, and energy production. Techniques to better support organ structure and function are being tested. No techniques are currently available to control proteolysis and the redistribution of skeletal muscle nitrogen. A great deal of research is still necessary in this field, which is still in its infancy.
Intraabdominal abscess induced multiple organ failure in 21 patients. Sepsis was most often due to perforation of the colon and was located with almost equal frequency in the upper and lower abdomen. Four patients died after single laparotomy for drainage. Seventeen were drained operatively more than once (average 3.4 operations) at mean intervals of 10 days. Sixteen of the 21 patients (76 percent) died with multiple organ failure despite drainage. Organ function improved temporarily in only one patient. Autopsy showed that pus had persisted or recurred in three patients. No significant predictors of survival were identified, although the advantage appears to lie with the younger patient in whom multiple organ failure develops relatively late after sepsis (mean 13 days) and who needs ventilatory assistance for less than 1 week. The location, size, and bacteriologic characteristics of abscesses do not appear to influence outcome. This study shows that early and repeated drainage of intraabdominal pus will not reverse multiple organ failure in the majority of patients.
As multiple-organ failure (MOF) has been generally associated with sepsis, the importance of bacterial sepsis was evaluated retrospectively in 55 trauma and 37 intra-abdominal-sepsis patients with MOF. The severity of MOF was graded, and an analysis was made of day of onset, incidence, severity, sequence, and mortality of organ failures. No difference was found between groups in sequence, severity, or mortality of organ failures. In contrast, bacterial sepsis was found in 65% of intra-abdominal-sepsis patients but only in 33% of trauma patients. It is concluded that sepsis is probably not the essential cause of MOF. Instead, an alternative hypothesis is presented involving massive activation of inflammatory mediators by severe tissue trauma or intra-abdominal sepsis, resulting in systemic damage to vascular endothelia, permeability edema, and impaired oxygen availability to the mitochondria despite adequate arterial oxygen transport.
Eighteen patients required hemodialysis after surgical treatment of ruptured abdominal aortic aneurysm. Review of the clinical events and autopsy findings showed a similar progression of organ system failure, beginning with pancreatic to pulmonary disease, and progressing to upper GI bleeding. A significant incidence of clinically silent (or at least undetected) major intraperitoneal disease was also noted. The lethality of renal failure after ruptured aneurysm is explained as a superimposition of preexisting chronic cardiovascular disease on the mechanical and metabolic consequences of the surgical procedure. Even though some of the mechanisms are well understood, their combination initiates a cycle which is difficult to interpret: mortality for this group of patients was greater than 90%.
A clinical syndrome of massive bleeding from acute multiple gastric ulcers associated with respiratory failure, hypotension, sepsis, and jaundice developed in eight of 150 consecutive patients admitted to the respiratory-surgical intensive care unit of the Beth Israel Hospital. These ulcers were almost exclusively located in the fundus of the stomach. Only one of these eight patients survived. Twenty-one gastric secretory studies performed in eighteen critically ill patients indicate that increased secretion of acid may be an important cause of this disease. One patient in whom acute gastric ulceration later developed had a maximally stimulated parietal cell mass in the basal state. Patients in whom this lethal complication develops and who do not respond to nonoperative therapy are probably best treated by gastric resection and vagotomy.
There are five major factors that determine outcome from disease: (1) disease type, (2) the severity of the disease, (3) the patient's age, (4) his prior health status, and (5) the therapy available. Evaluation of new treatments for various diseases is often done with little information on individual patients' severity. The most widely used method of controlling for acute severity fails to account for interaction among major organ systems and for important threshold effects found within physiologic measurements. To illustrate, we simulated a clinical trial comparing severity and outcome for two groups randomly chosen from 50 consecutive respiratory failure patients. Mean values for a variety of clinical, demographic, and physiologic measures were similar. A severity of disease classification, however, predicted differential mortality (25% vs 37%) that matched actual death rates. Uniform and accurate measurement of acute severity of disease in individual patients could improve the precision of clinical research.
Previous studies have suggested that the early application of positive end-expiratory pressure (PEEP) reduces the incidence of the adult respiratory-distress syndrome. We randomly assigned 92 patients with a known risk for this syndrome to receive mechanical ventilation either without PEEP (control) or with early PEEP at 8 cm H2O. These therapies continued for 72 hours unless respiratory distress developed or arterial oxygen tension was above 140 (fractional inspired oxygen concentration, 0.5) at 24 hours or later and remained at that level after removal of PEEP. The study was designed to have an 80 per cent probability of detecting a 60 per cent reduction in the incidence of the syndrome. The treatment groups were comparable in age, severity of injury, number and type of risk factors for adult respiratory-distress syndrome, and initial oxygenation. The syndrome developed in 11 of 44 patients given early PEEP (25 per cent) and in 13 of 48 control patients (27 per cent). The incidence of atelectasis, pneumonia, and barotrauma was the same in both groups, as was mortality. We found that the early application of PEEP at 8 cm H2O in high-risk patients had no effect on the incidence of the adult respiratory-distress syndrome or other, associated complications.
The common causes of death in the surgical intensive care unit (SICU) are infection, hemorrhage, and central nervous system trauma. Due to recent technological advances, many patients now survive the initial metabolic insult only to develop multisystem and organ failure (MSOF). The influence of sepsis on the patients with MSOF leads to a fatal outcome in the majority of cases. A retrospective analysis of 45 patients who died of sepsis and MSOF during 1981 and 1982 was performed. These patients comprised 58 per cent of 77 patients who died of MSOF. Demographic data from these 45 patients and from 32 nonseptic patients who also died of MSOF were compared, and no significant differences were noted. In 78 per cent of the patients who died of sepsis and MSOF, the main source of infection was either the respiratory or gastrointestinal tract. Skin contamination and catheter sepsis were identified in 13 per cent of patients as the main source of infection. Sixty four per cent of patients had positive blood cultures, and at least 50 per cent of those had more than one positive culture site. Predominant organisms isolated were gram-negative bacilli and gram-positive cocci. With the exception of Clostridia in two cases, no positive anaerobic cultures were noted in these patients. When the septic and nonseptic patients were compared, certain factors were identified that may have influenced the development of sepsis in these patients. These factors were poor nutritional status, diabetes mellitus, use of steroids, previous splenectomy, and an average total lymphocyte count below 700.(ABSTRACT TRUNCATED AT 250 WORDS)
Multiple system organ failure (MSOF) remains a principal cause of death after major operative procedures and/or severe trauma. We studied multiple parameters in 553 consecutive emergency surgical patients to determine the incidence of MSOF, the predisposing factors to MSOF, and the sequelae of MSOF. Thirty-eight patients had MSOF; mortality was 74% for these patients. Evaluation of multiple factors demonstrated that (1) MSOF is primarily due to infection, (2) the temporal sequence of organ failure is lung, liver, gastric mucosa, and kidney, and (3) MSOF is the most common fatal expression of uncontrolled infection.
Clinical features and specific aspects of treatment were evaluated in 612 patients with gram-negative bacteremia observed over a 10 year period. Coagulation abnormalities or thrombocytopenia were observed in 64 per cent of the patients. Evidence of disseminated intravascular coagulation (DIC) was found in approximately 10 per cent of them but was of sufficient severity to be associated with subcutaneous or visceral bleeding in 3 per cent of them. The frequency of coagulation abnormalities, other than DIC, was greater in patients with more severe underlying disease but DIC occurred with similar frequency irrespective of the severity of underyling host disease. Coagulation abnormalities of all types were associated with increased fatality rates. Hypothermia was noted in 13 per cent of the patients at the onset of bacteremia but was transient and was not associated with increased fatality. Failure to mount a febrile response greater than 99.6 degrees F within the first 24 hours of bacteremia was associated with a significant increase in fatality rates. Prior corticosteroid therapy diminished the febrile response to bacteremia. Age, underlying host disease, granulocytopenia, congestive heart failure, diabetes mellitus, renal insufficiency, nosocomial infections, and antecedent treatment with antibiotics, corticosteroids, and antimetabolites significantly increased fatality rates. Appropriate antibiotic treatment reduced the fatality rate of those with bacteremia by approximately one-half among patients in each category of severity of underlying host disease. In addition, it was shown that early appropriate antibiotic therapy also reduced the frequency with which shock developed by one half. Even after development of shock, appropriate antibiotic therapy significantly reduced fatality rates. The use of combinations of antibiotics could not be demonstrated to significantly improve survival rates. Minimal differences in therapeutic efficacy could be demonstrated between individual antibiotics and various combinations of antimicrobials. Shock occurred in approximately 40 per cent of the patients and its frequency was not influenced by the species of etiologic agent. Contrary to previous reports, corticosteroid therapy in patients with shock did not enhance survival and treatment with an average of 4.0 g/day of hydrocortisone or its equivalents was associated with a significant increase in fatality rates.
One hundred thirty-six patients meeting our criteria for one or more of eight clinical conditions were prospectively observed for the development of the adult respiratory distress syndrome. A high risk population was identified, including those with sepsis syndrome (38 percent), documented aspiration of gastric contents (30 percent), multiple emergency transfusions (24 percent), and pulmonary contusion (17 percent). The risk from multiple major fractures appeared low but contributed to the risk from other factors. The risk associated with just one factor (25 percent) was compounded by the presence of two (42 percent) and three (85 percent) simultaneous factors, and this finding was more predictive of ARDS than the injury severity score or initial arterial oxygenation. Of the ARDS cases, 76 percent occurred in the initial 24 hours after meeting the criteria. ARDS did not occur after 72 hours unless there was late development of sepsis (3 of 136 patients).
A system has been constructed to evaluate the design, implementation, and analysis of randomized control trials (RCT). The degree of quadruple blinding (the randomization process, the physicians and patients as to therapy, and the physicians as to ongoing results) is considered to be the most important aspect of any trial. The analytic techniques are scored with the same emphasis as is placed on the control of bias in the planning and implementation of the studies. Description of the patient and treatment materials and the measurement of various controls of quality have less weight. An index of quality of a RCT is proposed with its pros and cons. If published papers were to approximate these principles, there would be a marked improvement in the quality of randomized control trials. Finally, a reasonable standard design and conduct of trials will facilitate the interpretation of those with conflicting results and help in making valid combinations of undersized trials.
Sepsis syndrome: a valid clinical entity
- Bone
Effect of high-dose glucocorticoid therapy on mortality in patients with clinical signs of systemic sepsis
- Veterans Administration Systemic Sepsis Cooperative Study Group
Multiple organ failure during interleukin-2 and LAK cell infusion
- Sculier