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Introduction: Febrile neutropenia, a commonly occurring entity in patients (pts) with HM, is treated empirically with antibiotics due to a high risk of developing septic shock. Currently, there is no way to predict which hospitalized pts with febrile neutropenia are at greatest risk of developing septic shock. Clinicians have traditionally used systemic inflammatory response syndrome (SIRS) criteria (≥ 2 of the following: RR > 20, HR >90, Temp > 38C or 12k or Methods: We tested the association of lactate, tachypnea, and tachycardia with the development of septic shock in hospitalized adult HM pts (age 18–83) in a nested, case-control design within a prospective, single-center, cohort study. Vital signs and lactate were measured during episodes of febrile neutropenia (Temp > 100.4 & ANC < 1000) during hospitalization. We defined an elevated lactate as a level ≥ 2.0 mmol/L. The study endpoint was the development of septic shock, defined as a document or suspected infection resulting in hypotension unresponsive to 1.5 L of IV fluids. The case-control design with incidence-density sampling allowed for maximal efficiency and minimal bias. Controls were matched on length of stay at the time of septic shock in a 4:1 ratio to achieve 80% power to detect an OR (odds ratio) of 2.5. Using multivariable logistic regression and receiver operating curve (ROC) analysis, we evaluated the association of SIRS and lactate with the development of septic shock within 48 hrs following their measurement. Results: Of the 547 pts enrolled, 46 (8.4%; 95% confidence interval [CI]: 6.2–10.9) developed septic shock. Baseline characteristics including age, vital signs, ANC, medications, and lactate were similar between the groups. The mean baseline lactate (1.0 mmol/L; 95% CI: 0.5–2.0) for the cohort was similar to our hospital’s normal range (.7–2.1mmol/L). In univariate analysis of HR, RR and lactate, only tachypnea (RR>20) (OR 5.9; 95% CI: 2.0–16.9, p =.001) and elevated lactate level (OR 18.4; 95% CI: 4.1–81.6, p Conclusions: In febrile neutropenic pts, measurement of tachypnea is the only SIRS criteria with independent prognostic importance for the development of septic shock. In addition to RR, measurement of serum lactate (a valid, inexpensive, readily available laboratory test) at the time of febrile neutropenia, adds significant value in the prediction of which HM pts are at increased risk of developing septic shock. Although further study is required to validate these results, routine measurement of lactate may help identify pts who may benefit from increased monitoring and early intervention strategies.

Pts with hematologic malignancies (HM) are at high risk of developing SS and sepsis-related mortality. The diagnosis of sepsis requires suspicion of infection accompanied by at least two signs of systemic inflammation. The SIRS criteria were devised to improve the early bedside detection of sepsis and provide objective inclusion criteria for clinical research. Cut-point values based on consensus opinion are: HR >90, Temp > 100.4 or 20, and WBC >12k or Methods: The association between the SIRS and SS was evaluated in hospitalized adult pts (age 18–83) with HM in a prospective single-center, nested case-control study. The primary outcome was SS, defined as an infection resulting in cardiovascular or respiratory failure. Vital signs were performed every eight hours. Of the 547 pts who consented for the study, 54 developed SS (9.9% CI 7.7–12.7%). Using incidence density sampling, 211 controls were selected by matching on length of stay at time of SS. Evidence-based cut-points were then derived for the individual SIRS variables by examining risk estimates based on variable percentiles. Results: At hospital admission, HR, RR, BP, WBC, ANC, age, diagnosis, and transplant status were similar between the groups. In univariable analysis (24° prior to SS), significance of the four individual SIRS variables were: HR (p=.001), RR (p 20, OR 8.3, CI 2.8–24.4 p Conclusions: This study is the first to evaluate and define the test characteristics of the SIRS criteria in hospitalized pts with HM. The rationale for excluding HM patients from SS clinical trials based on diagnostic concerns should be revisited when planning future SS studies. Fever, tachycardia and tachypnea seem most predictive in this population. These results suggest that cut-points for significant SIRS variables can be redefined to improve the specificity of the SIRS score. Additional markers for the early detection of SS may further improve upon SIRS in HM pts. SIRS Score Sensitivity % (95 CI) Specificity LR(+) 1 98 (97–99) 12 (8–18) 1.1 2 76 (71–81) 60 (54–66) 1.9 3 39 (33–45) 91 (88–94) 4.3 4 7 (4–11) 99 (99–100) 15.6