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Systemic inflammatory response syndrome caused by chronic salicylate intoxication.

Systemic inflammatory response syndrome (SIRS) is characterized by body temperature abnormalities, tachypnea or hyperventilation, tachycardia, and leukocytosis or leukopenia. Although it is typically associated with a serious infection and referred to as sepsis, SIRS can stem from noninfectious causes, as well. We report the cases of four patients with toxic serum levels of salicylate (33.5 to 67.6 mg/dL) and SIRS, and we discuss mechanisms responsible for SIRS. Our patients showed temperature disturbances (35.5 degrees C to 39.8 degrees C), noncardiogenic pulmonary edema, and mixed acid base disturbances. Other abnormalities included coagulopathy (disseminated intravascular coagulation), encephalopathy, and hypotension. All four patients recovered from SIRS, probably due to early recognition and treatment; only one patient did not survive the hospitalization. Chronic salicylate toxicity should be considered as a cause of SIRS in the absence of a source of infection, since survival appears to be dependent on prompt diagnosis and management.

Acid-Base Imbalance↗

The systemic inflammatory response syndrome in acute liver failure.

The systemic inflammatory response syndrome (SIRS) in acute liver failure (ALF), in which infection is common, has not been studied. In this study, SIRS components were recorded on admission and during episodes of infection, in 887 ALF patients admitted to a single center during an 11-year period. Overall, 504 (56.8%) patients manifested a SIRS during their illness, with a maximum of 1, 2, and 3 concurrent SIRS components in 166, 238, and 100 patients, respectively. In 353 (39.8%) patients who did not become infected, a SIRS on admission was associated with a more critical illness, subsequent worsening of encephalopathy, and death. Infected patients more often developed a SIRS and one of greater magnitude. The magnitude of the SIRS in 273 patients with bacterial infection correlated with mortality, being 16.7%, 28.4%, 41.2%, and 64.7% in patients with 0, 1, 2, and 3 maximum concurrent SIRS components, respectively. Similar correlations with mortality were seen for SIRS associated with fungal infection, bacteremia, and bacterial chest infection. Fifty-nine percent of patients with severe sepsis died, as did 98% of those with septic shock. A significant association was found between progressive encephalopathy and infection. Infected patients with progressive encephalopathy manifested more SIRS components than other infected patients. For patients with a SIRS, the proportions of infected and noninfected patients manifesting worsening encephalopathy were similar. In ALF, the SIRS, whether or not precipitated by infection, appears to be implicated in the progression of encephalopathy, reducing the chances of transplantation and conferring a poorer prognosis.

Acetaminophen↗

Acute systemic inflammatory response syndrome in subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Systemic inflammatory response syndrome (SIRS) without infection is a well-known phenomenon that accompanies various acute cerebral insults. We sought to determine whether the initial SIRS score was associated with outcome in subarachnoid hemorrhage (SAH). METHODS: In 103 consecutive patients with SAH, the occurrence of SIRS was assessed according to the presence of >/=2 of the following: temperature of <36 degrees C or >38 degrees C, heart rate of >90 bpm, respiratory rate of >20 breaths/min, and white blood cell count of <4000/mm(3) or >12 000/mm(3). SIRS criteria and other prognostic parameters were evaluated as predictors of dichotomous Glasgow Outcome Scale score. RESULTS: SIRS was highly related to poor clinical grade (Hunt and Hess clinical grading scale), a large amount of SAH on CT (Fisher CT group), and high plasma glucose concentration on admission. By univariate analysis, the occurrence of SIRS was associated with higher mortality and morbidity rates than was the nonoccurrence (P<0.001). Among individual SIRS criteria, heart rate (P=0.003), respiration rate (P=0.003), and white blood cell count (P=0.03) were significant outcome predictors. By multivariate logistic regression analysis, the presence of SIRS independently predicted outcome. SIRS carried an increased risk of subsequent intracranial complications such as vasospasm and normal pressure hydrocephalus, as well as systemic complications. CONCLUSIONS: In SAH patients, SIRS on admission reflected the extent of tissue damage at onset and predicted further tissue disruption, producing clinical worsening and, ultimately, a poor outcome.

Acute Disease↗

Endotoxin immunity and the development of the systemic inflammatory response syndrome in critically ill children.

BACKGROUND: The systemic inflammatory response syndrome (SIRS) may be triggered by endotoxin. Humans have antibodies directed against the core of endotoxin (endotoxin core antibodies, EndoCAb) that appear to be protective following surgery and in sepsis. We hypothesised that children with elevated antibodies to endotoxin core would be less likely to develop SIRS in their initial period on intensive care. Because of the existing literature we defined two sub-groups according to the primary reason for ICU admission: infection and non-infection. METHODS: We recruited 139 consecutive patients admitted to a paediatric intensive care unit (PICU) with more than one organ failure for longer than 12 h as part of another study. Patients were classified on admission to PICU as having an infectious or a non-infections diagnosis. The occurrence of SIRS within 48 h of admission was recorded along with detailed clinical and demographic data, EndoCAb concentration and the potential confounding variables C-reactive protein and mannose-binding lectin. RESULTS: In the 71 patients admitted without infection (primarily post-operative and head injured) IgG EndoCAb was significantly lower in patients who developed SIRS than those who did not (72 vs. 131 MU/ml), independent of potential confounding variables. In patients with infection there was no significant difference in IgG EndoCAb between children developing SIRS and those who did not (111 vs. 80 MU/ml). CONCLUSION: Head injured and post-operative patients admitted to PICU who develop early SIRS have significantly lower serum IgG EndoCAb levels than those who do not.

Adolescent↗

Air embolism as a cause of the systemic inflammatory response syndrome: a case report.

We describe a case of systemic inflammatory response syndrome associated with air embolism following the removal of a central line catheter, coupled with a deep inspiratory maneuver. The presence of a patent foramen ovale allowed the passage of a clinically significant amount of air from the venous circulation to the systemic circulation. The interaction of air with the systemic arterial endothelium may have triggered the release of endothelium-derived cytokines, resulting in the physiologic response of systemic inflammatory response syndrome.

Aged↗

Role of the neutrophil in the development of systemic inflammatory response syndrome and sepsis following abdominal aortic surgery.

INTRODUCTION: There is evidence to suggest that the polymorphonuclear neutrophil (PMN) plays a critical early step in the development of the ischaemia-reperfusion syndrome, the systemic inflammatory response syndrome (SIRS) and sepsis. The PMN receptor CD16 plays an important role in phagocytosis, cell-mediated cytotoxicity and the release of free radicals and proteolytic enzymes. The aim of this study was to determine whether there is any relationship between PMN CD16 expression, phagocytosis and the development of sepsis. METHODS: Fifty patients who underwent elective infrarenal abdominal aortic aneurysm repair were studied. Venous blood was taken before operation, throughout surgery and for 7 days after operation. CD16 expression was measured, unstimulated and following further stimulation, by means of flow cytometry. Phagocytosis was determined using flow cytometry. RESULTS: Some 36 patients had an uncomplicated recovery; 14 developed SIRS or sepsis. There was no difference between the two groups with respect to nutritional, co-morbid or technical factors. In the group that developed septic complications after operation, the level of PMN CD16 expression was significantly higher before surgery (mean channel fluorescence (MCF) 30.2 versus 10.4; P < 0.05, Mann-Whitney U test) and throughout the postoperative period. Surgery produced no change in CD16 expression. After operation, stimulation of PMNs in the septic group resulted in a fall in CD16 expression (40.8 versus 20.4 MCF; P < 0.05, Mann-Whitney U test); surgery produced no change in the level of expression in the uncomplicated group. CONCLUSION: This study provides evidence of phenotypic and functional differences in neutrophil behaviour in patients who develop sepsis following aneurysm surgery.

Aged↗

Dysregulated expression of neutrophil apoptosis in the systemic inflammatory response syndrome.

OBJECTIVE: To study the effect of the systemic inflammatory response syndrome (SIRS) or major elective surgery on the apoptosis of circulating polymorphonuclear neutrophils because an activated inflammatory response is terminated, in part, through the programmed cell death, or apoptosis, of its effector cells. DESIGN: A prospective inception cohort study. SETTING: A mixed surgical and medical intensive care unit of an adult tertiary care hospital. PATIENTS: Sixteen patients with SIRS, 7 uninfected patients who had undergone elective aortic aneurysmectomy, and 8 healthy laboratory control subjects. INTERVENTIONS: Serial blood samples were drawn for evaluation of neutrophil apoptosis, activational state, and surface receptor expression by flow cytometry. MAIN OUTCOME MEASURES: Spontaneous apoptosis was significantly delayed in neutrophils from patients with SIRS (8.6%+/-6.8%) and patients who had undergone elective aortic aneurysmectomy (11.0%+/-5.0%) when compared with controls (34.9%+/-6.8%). These neutrophils were activated as evidenced by enhanced respiratory burst activity and augmented surface expression of CD11b. Apoptosis in response to engagement of cell surface Fas (also known as CD95 or APO-1) with an agonistic antibody was blunted. Plasma from patients with SIRS or patients who had undergone elective aortic aneurysmectomy suppressed the apoptotic responses of control neutrophils (plasma from patients with SIRS, 18.8%+/-10.3%; plasma from patients who had undergone elective aortic aneurysmectomy, 20.0%+/-6.1%; P<.01). Western blot analysis showed normal expression of the key proapoptotic proteases, interleukin 1beta converting enzyme and CPP32 (also known as YAMA, apopain, and caspase 3), indicating that delayed apoptosis was not a consequence of decreased levels of proapoptotic enzymes. CONCLUSIONS: Circulating neutrophils from patients with SIRS or from patients who have undergone major elective surgery show delayed expression of constitutive programmed cell death, and antiapoptotic factors are present in the general circulation. While prolonged neutrophil survival may represent an appropriate adaptive response to injury, the presence of activated and apoptosis-resistant cells in an antiapoptotic environment may contribute to the systemic inflammatory injury characteristic of SIRS and predispose to the development of the multiple organ dysfunction syndrome.

APACHE↗

Systemic inflammatory response syndrome after cardiac operations.

BACKGROUND: A systemic inflammatory response after open heart operation may be responsible for hyperdynamic circulatory instability and organ dysfunction. To what extent mediator release is involved needs to be clarified. METHODS: Ten patients with postoperative hyperdynamic circulatory dysregulation (group I) requiring application of alpha-constrictors and 10 patients with routine cardiac procedures and stable postoperative hemodynamic indices (group II) were analyzed for mediator release and metabolic and hemodynamic changes until the third postoperative day. RESULTS: Group I patients showed a significantly increased cardiac index and decreased systemic vascular resistance after bypass (cardiac index, group I: 5.2 +/- 1.2 L.min-1.m-2, group II: 2.5 +/- 1.6 L.min-1.m-2; systemic vascular resistance, group I: 495 +/- 204 dyne.s. cm-5, group II: 1,356 +/- 466 dyne.s.cm-5) and at 3 hours (cardiac index, group I: 4.4 +/- 0.8 L.min-1.m-2, group II: 2.9 +/- 0.6 L.min-1.m-2; systemic vascular resistance, group I: 567 +/- 211 dyne.s.cm-5, group II: 1,053 +/- 273 dyne.s.cm-5). Significantly higher serum levels of interleukin-6 were assessed in group I (postbypass, group I: 6,812 +/- 9,293 pg/mL, group II: 295 +/- 303 pg/mL; 3 hours, group I: 3,474 +/- 5,594 pg/mL, group II: 286 +/- 296 pg/mL). Concentrations of elastase, tumor necrosis factor, soluble tumor necrosis factor receptor, and interleukin-8 were elevated in group I (not significant). Early postoperative levels of soluble E-selectin and soluble intercellular adhesion molecule were also higher in group I (not significant). Continuously increased levels of endotoxin could be detected in only 3 of 10 patients in group I. Severe lactic acidosis (> or = 5 mmol/L) occurred in group I only. CONCLUSIONS: Postoperative hyperdynamic instability after open heart operations appears to be associated with a certain pattern of mediator release. In particular, interleukin-6 appears to be involved in circulatory dysregulation and metabolic derangement.

Acidosis, Lactic↗

[Systemic inflammatory response syndrome and primary of spontaneous intracerebral haemorrhage].

OBJECTIVE: Systemic inflammatory response syndrome (SIRS) without infection is a well known phenomenon that accompanies various acute cerebral insults. We in tented to determine whether SIRS was associated with outcome in patients with spontaneous intracerebral hemorrhage. PATIENTS AND METHODS: In patients with intracerebral hemorrhage, the occurrence of SIRS was assessed according to the guidelines of the 1992 Consensus Conference. SIRS criteria and other prognostic parameters were evaluated as predictors of final outcome. RESULTS: SIRS was highly related to poor clinical grade (Glasgow coma scale), hemorrhage volume on CT scan and intraventricular extension of hemorrhage. By univariate analysis,the occurrence of SIRS was associated with higher mortality and morbidity rates than was the nonoccurrence (p<0.005). CONCLUSIONS: In patients with intracerebral hemorrhage, SIRS reflected the extent of tissue damage and predicted a poor outcome.

Adult↗

Glycyrrhizin inhibits the manifestations of anti-inflammatory responses that appear in association with systemic inflammatory response syndrome (SIRS)-like reactions.

In association with the systemic inflammatory response syndrome (SIRS), anti-inflammatory response syndrome is commonly manifested in patients with trauma, burn injury, and after major surgery. These patients are increasingly susceptible to infection with various pathogens due to the excessive release of anti-inflammatory cytokines from anti-inflammatory effector cells. Recently, CC-chemokine ligand 2 (CCL2) found in the sera of mice with pancreatitis was identified as an active molecule for SIRS-associated anti-inflammatory response manifestation. Also, the inhibitory activity of glycyrrhizin (GL) on CCL2 production was reported. Therefore, the effect of GL on SIRS-associated anti-inflammatory response manifestation was investigated in a murine SIRS model. Without any stimulation, splenic T cells from mice 5 days after SIRS induction produced cytokines associated with anti-inflammatory response manifestation. However, these cytokines were not produced by splenic T cells from SIRS mice previously treated with GL. In dual-chamber transwells, IL-4-producing cells were generated from normal T cells cultured with peripheral blood polymorphonuclear neutrophils (PMN) from SIRS mice. However, IL-4-producing cells were not generated from normal T cells in transwell cultures performed with PMN from GL-treated SIRS mice. CCL2 was produced by PMN from SIRS mice, while this chemokine was not demonstrated in cultures of PMN from SIRS mice treated with GL. These results indicate that GL has the capacity to suppress SIRS-associated anti-inflammatory response manifestation through the inhibition of CCL2 production by PMN.

Animals↗

The sequential organ failure assessment score as a useful predictor for estimating the prognosis of systemic inflammatory response syndrome patients being treated with extracorporeal blood purification.

Systemic inflammatory response syndrome (SIRS) is a major cause of morbidity and mortality in critically ill patients. Extracorporeal blood purification procedures are becoming important for treating these patients. However, the cost of these procedures is high. Therefore, a prognostic marker would be helpful. To establish the reliability of the Sequential Organ Failure Assessment (SOFA) score as a prognostic indicator, we evaluated daily changes in the SOFA score of 40 SIRS patients who needed blood purification procedures such as continuous renal replacement therapy (CRRT), endotoxin adsorption, bilirubin adsorption, and/or plasma exchange. Twenty patients survived and 20 died. Although the baseline scores of the two groups (survivors and non-survivors) did not differ, both the maximum value of the SOFA score and the DeltaSOFA score (the difference between the maximum SOFA and baseline SOFA scores) were significantly higher in the non-survivor group. The mortality rate among patients with a maximum SOFA score greater than or equal to 18 or a DeltaSOFA score greater than or equal to 3 was higher than for the rest of the patients. The changes in the SOFA score correlated well with the outcomes of the SIRS patients. The maximum SOFA score and the DeltaSOFA score are therefore likely to be useful prognostic markers.

APACHE↗

The effects of leucodepletion in patients who develop the systemic inflammatory response syndrome following cardiopulmonary bypass.

The development of the systemic inflammatory response syndrome (SIRS) is associated with increased morbidity and mortality. Numerous anticytokine trials have failed to demonstrate any outcome benefit and there has been little evidence of improvement in the prognosis of this condition over the past 20 years. This study examines the effect of using a white cell filter designed to remove polymorphonuclear cells (PMNs) in patients who developed SIRS 36 h after cardiopulmonary bypass (CPB). Twenty-four patients were randomized to receive either leucofiltration (LF) or control therapy (CT). The two groups were well matched at study entry in terms of age, severity of illness and length of time on CPB. LF patients received 60 min filtration periods using a venovenous extracorporeal circuit at a flow rate of 200 ml/min with the cycle repeated every 12 h while SIRS and other entry criteria were met. CT patients received standard therapy. LF patients received an average of 4.2 cycles (range 1-8) and, after 15 min filtration, the total leucocyte count had fallen from 16.2 +/- 5.3 to 10.4 +/- 3.3 x 10(9)/l and PMN from 14.4 +/- 5.2 to 8.3 +/- 4.2 x 10(9)/l. The mean platelet count changed from 127 +/- 87 to 117 +/- 82 x 10(9)/l. No adverse effects related to leucodepletion were observed. There was no difference between the groups in either mortality or length of stay at the intensive care unit or at hospital discharge. Organ function was assessed regularly during the study period and significant changes occurred only in respiratory and renal function. In the LF patients, respiratory function assessed by change in hypoxaemia index from baseline and renal function assessed by serum creatinine showed significant treatment effects compared to CT patients (p < 0.01, < 0.01 respectively); three CT patients, but no LF patients, received haemofiltration during the study period. Leucofiltration safely and effectively removes circulating PMNs from patients with SIRS following CPB. This may result in improved pulmonary and renal function in these patients. Further studies are required of the kinetics and phenotypic characteristics of PMN removal by leucofiltration and a larger multicentre study will be necessary to determine whether this novel therapy has a significant outcome benefit in critically ill patients with SIRS.

Aged↗

Systemic inflammatory response syndrome and nosocomial infection in trauma.

BACKGROUND: Admission systemic inflammatory response syndrome (SIRS) score has been previously reported to be an accurate predictor of infection and outcome in trauma. However, the data were limited to the first 7 days of admission. Our objective in this follow-up study was to prospectively evaluate the utility of daily SIRS scores in the second and third week of admission as compared with the first week in prediction of nosocomial infection and outcome in high-risk trauma patients. METHODS: Prospective data were collected on 1,277 consecutive trauma patients admitted during a 28-month period to the intensive care unit. SIRS scores were calculated daily for the first week and every other day for the following 2 weeks. Patients were categorized into SIRS occurring "early" (week 1), "middle" (week 2), and "late" (week 3). Centers for Disease Control and Prevention guidelines were used for the diagnosis of infection. Multivariate linear and logistic regression analyses were utilized for statistical analyses, controlling for the covariates of age, Injury Severity Score, and admission Glasgow Coma Scale score. RESULTS: The trauma cohort included patients with blunt injuries (84%) and penetrating injuries (16%). The mean age was 43 +/- 21 years with an overall mortality of 14.7%. Nosocomial infection developed in 580 (45.4%) of the study patients (respiratory site most common) with a total of 1,001 infections (some patients with multiple infections). SIRS (defined as SIRS score >/=2) was common, with 92.4% of patients manifesting SIRS at admission. SIRS was most prevalent during the first week postinjury (91% of patients manifesting SIRS), decreasing to 69% and 50% during postinjury weeks 2 and 3. SIRS was more common in patients who acquired nosocomial infections compared with noninfected patients. Logistic regression analysis confirmed that patients with "middle" SIRS during week 2 (odds ratio [OR] 17.62, confidence interval [CI] 12.95-23.97, p < 0.0001, receiver operating characteristic [ROC] 0.83) and "late" SIRS during week 3 (OR18.12, CI 12.71-25.84, p < 0.0001, ROC 0.81) had significantly greater risk for nosocomial infection compared with patients with "early" SIRS during week 1 (OR 4.55, CI 2.57-8.06, p < 0.0001, ROC 0.65) postinjury. CONCLUSION: SIRS is predictive of nosocomial infection in trauma through postinjury day 21. Nosocomial infection should be considered as a treatable cause of SIRS in trauma patients, and early diagnostic interventions should be initiated to evaluate for potential causes.

Adult↗

Toward a theory regarding the pathogenesis of the systemic inflammatory response syndrome: what we do and do not know about cytokine regulation.

OBJECTIVES: The systemic inflammatory response syndrome (SIRS) is the massive inflammatory reaction resulting from systemic mediator release that may lead to multiple organ dysfunction. The objective of this review article is to analyze the roles of cytokines, cytokine production, and the relationship of cytokine production to the development of SIRS. DATA SOURCES: Previous research and clinical studies related to cytokines and their relationship to SIRS. STUDY SELECTION: From the studies reviewed, three critical questions are addressed. First, what is the definition of increased cytokine concentrations? Second, what other systemic illnesses besides sepsis can alter cytokine concentrations? Third, what are the right cytokines to measure? DATA SYNTHESIS: This article postulates a three-stage development of SIRS, in which stage 1 is a local production of cytokines in response to an injury or infection. Stage 2 is the protective release of a small amount of cytokines into the body's circulation. Stage 3 is the massive systemic reaction where cytokines turn destructive by compromising the integrity of the capillary walls and flooding end organs. CONCLUSIONS: While cytokines are generally viewed as a destructive development in the patient that generally leads to multiple organ dysfunction, cytokines also protect the body when localized. It will be necessary to study the positive effects of cytokines while also studying their role in causing SIRS. It will also be important to investigate the relationship between cytokines and their blockers in SIRS.

Animals↗

Systemic inflammatory response syndrome treatment by powdered sorbent pheresis: the BioLogic-Detoxification Plasma Filtration System.

Systemic inflammatory response syndrome (SIRS) is one of the most common causes of death in intensive care unit patients. The detoxification plasma filtration (DTPF) system (HemoCleanse, Inc., West Lafayette, IN) combines the DT hemodiabsorption system in series with a push-pull pheresis PF system (a suspension of powdered sorbents surrounding 0.5 microm plasma filter membranes). Bidirectional plasma flow (at 80-100 ml/min) across the PF membranes provides direct contact between plasma proteins and powdered sorbents, as well as clearance of cytokines (tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6) at a rate of 15-25 ml/min, without evidence of saturation for 90 minutes. In a U.S. Food and Drug Administration approved study we treated eight patients with SIRS and organ failure with a single DTPF treatment, using powdered charcoal as sorbent in four patients and powdered charcoal and silica in four patients. Treatments proceeded for 6 hours with proper heparin anticoagulation (activated clotting time 250-300 sec) and appeared safe. All patients improved during the treatments and each had increased blood pressure and decreased need for pressor agents. Plasma cytokine levels stabilized or decreased during treatment and were significantly lower the morning after treatment. Multiple organ dysfunction (MOD) and Acute Physiology Chronic Health Evaluation II scores and organ function gradually improved in most patients, and two patients survived for more than 28 days and two for more than 14 days. The DTPF System may prove beneficial in treatment of patients with sepsis.

Adult↗