Hospital Mortality In Sepsis Research Articles

U-shaped correlation of lymphocyte count with all-cause hospital mortality in sepsis and septic shock patients: a MIMIC-IV and eICU-CRD database study

BackgroundIn sepsis, the relationship between lymphocyte counts and patient outcomes is complex. Lymphocytopenia and lymphocytosis significantly influence survival, illustrating the dual functionality of lymphocytes in responding to infections. This study investigates this complex interaction, focusing on how variations in lymphocyte counts correlate with all-cause hospital mortality among sepsis patients.MethodsThis retrospective cohort study analyzed data from two extensive critical care databases: the Medical Information Mart for Intensive Care IV 2.0 (MIMIC-IV 2.0) from Beth Israel Deaconess Medical Center, Boston, Massachusetts, and the eICU Collaborative Research Database (eICU-CRD), which was Multi-center database from over 200 hospitals across the United States conducted by Philips eICU Research Institute. We included adult patients aged 18 years and older who met the Sepsis-3 criteria, characterized by documented or suspected infection and a Sequential Organ Failure Assessment (SOFA) score of 2 or higher. Sepsis patients were categorized into quartiles based on lymphocyte counts. The primary outcome was all-cause mortality in the hospital, with 90 and 60-day all-cause mortality as the secondary outcomes. Univariable and multivariable Cox proportional hazard regressions were utilized to assess lymphocyte counts' impact on hospital mortality. An adjusted restricted cubic spline (RCS) analysis was performed to elucidate this relationship further. Subgroup analyses were also conducted to explore the association across various comorbidity groups among sepsis and septic shock patients.ResultsOur study included 37,054 patients, with an observed in-hospital mortality rate of 16.6%. Univariable and multivariable Cox proportional hazard regression models showed that lymphocyte counts were independently associated with in-hospital mortality (HR = 1.04, P < 0.01; HR = 1.06, P < 0.01). RCS regression analysis revealed a U-shaped relationship between lymphocyte levels and hospital mortality risk in sepsis and septic shock patients (P for overall < 0.001, P for nonliner < 0.01; P for overall = 0.002, P for nonliner = 0.014). Subgroup analyses revealed that elevated lymphocyte counts correlated with increased hospital mortality among sepsis patients with liver disease and requiring renal replacement therapy (P for overall = 0.021, P for nonliner = 0.158; P for overall = 0.025, P for nonliner = 0.759). These findings suggest that lymphocytes may have enhanced prognostic value in specific subsets of critically ill sepsis patients.ConclusionOur findings demonstrate that lymphocyte counts are a significant independent predictor of hospital mortality in sepsis and septic shock patients. We observed a U-shaped association between lymphocyte levels and mortality risk, indicating that high and low counts are linked to increased mortality. This result highlights the complex role of lymphocytes in sepsis outcomes and suggests the need for further investigation into the underlying mechanisms and potential therapeutic approaches. Integrating lymphocyte count assessment into risk stratification algorithms and clinical decision support tools could enhance the early identification of high-risk sepsis patients.

The neutrophil-to-lymphocyte ratio levels over time correlate to all-cause hospital mortality in sepsis

ObjectiveThis research aims to investigate the prognosis value using the time-weighted average neutrophil-to-lymphocyte ratio (TWA-NLR) for predicting all-cause hospital mortality among sepsis patients. Data were analyzed through the use of the eICU Collaborative Research Database (eICU-CRD 2.0) as well as Medical Information Mart for Intensive Care IV 2.2 (MIMIC-IV 2.2). MethodsSeptic patients from both eICU-CRD 2.0 as well as MIMIC-IV 2.2 databases were included. The neutrophil-to-lymphocyte ratios (NLR) were available for analysis, utilizing complete blood counts obtained on days one, four, and seven following ICU admission. The TWA-NLR was computed at the end of the seven days, and patients were then stratified based on TWA-NLR thresholds. 90-day all-cause mortality during hospitalization was the primary objective, with 60-day all-cause hospital mortality as a secondary objective. The correlation between TWA-NLR and sepsis patients' primary outcome was analyzed using univariable and multivariable Cox proportional hazard regressions. A restricted cubic spline (RCS) analysis was conducted in an attempt to confirm this association further, and subgroup analyses were employed to evaluate the correlation across various comorbidity groups. Results3921 patients were included from the eICU-CRD 2.0, and the hospital mortality rate was 20.8 %. Both multivariable as well as univariable Cox proportional hazard regression analyses revealed that TWA-NLR was independently correlated with 90-day all-cause hospital mortality, yielding a hazard ratio (HR) of 1.02 (95 % CI 1.01–1.02, P-value<0.01) as well as 1.12 (95 % CI 1.01–1.15, P-value<0.01), respectively. The RCS analysis demonstrated a significant nonlinear relationship between TWA-NLR and 90-day all-cause hospital mortality risk. The study subjects were divided into higher (>10.5) and lower (≤10.5) TWA-NLR cohorts. A significantly decreased incidence of 90-day all-cause hospital mortality (HR = 0.56, 95 % CI 0.48–0.64, P-value<0.01) and longer median survival time (40 days vs 24 days, P-value<0.05) were observed in the lower TWA-NLR cohort. However, septic patients with chronic pulmonary (interaction of P-value = 0.009) or renal disease (interaction of P-value = 0.008) exhibited significant interactive associations between TWA-NLR and 90-day all-cause hospital mortality, suggesting the predictive power of TWA-NLR may be limited in these subgroups. The MIMIC-IV 2.2 was utilized as a validation cohort and exhibited a similar pattern. ConclusionOur findings suggest that TWA-NLR is a powerful and independent prognostic indicator for 90-day all-cause hospital mortality among septic patients, and the TWA-NLR cutoff value may prove a useful method for identifying high-risk septic patients.

Effect of low-dose hydrocortisone and inhaled nitric oxide on inflammatory mediators and local pulmonary metalloproteinases activity in LPS-induced sepsis in piglets

Hospital mortality in sepsis varies between 30–45%. It has been shown that administration of inhaled nitric oxide (iNO) and intravenous corticosteroid in a porcine endotoxemia model attenuated the systemic inflammatory response. We explored the anti-inflammatory effect of a double-treatment strategy (iNO + low-dose steroid) on the lungs in a long-term porcine endotoxic shock model. As metalloproteinases (MMPs) are involved in the initiation of multiple organ dysfunction in septic shock, we evaluated the influence of this combination therapy on MMP2 and MMP9 activity and proIL-1β maturation. A shock-like condition was established in 23 animals by continuous infusion of E. coli lipopolysaccharide (LPS) for 10 h. Then the animals were observed for 10 h. Twelve pigs received iNO and hydrocortisone (iNO treatment started 3 h after the initial LPS infusion and continued until the end of the experiment). Eleven pigs were controls. Pigs treated with iNO and hydrocortisone displayed less inflammatory infiltrates in the lungs than the controls and a lower level of IL-1β. The proMMP2 was significantly decreased in the iNO and hydrocortisone group. The amount of an active MMP9 (~ 60 kDa) was decreased in the iNO and hydrocortisone group. Total gelatinolytic activity was lower in the iNO and hydrocortisone group. Reduced MMP activity was accompanied by a 2.5-fold decrease of the active IL-1β form (17 kDa) in the pulmonary tissue of iNO combined with hydrocortisone exposed pigs. We demonstrated that in a porcine endotoxemia model the NO inhalation combined with intravenous hydrocortisone led to the attenuation of the inflammatory cascade induced by bacterial LPS. The decrease in pulmonary MMPs activities was accompanied by reduced proIL-1β processing.

The effect of dobutamine in sepsis: a propensity score matched analysis

BackgroundThe use of dobutamine in patients with sepsis is questionable currently. As the benefit of dobutamine in septic patients is unclear, we aimed to evaluate whether the use of dobutamine was associated with decreased hospital mortality in sepsis patients.MethodsBased on the analysis of MIMIC III public database, we performed a big-data, real world study. According to the use of dobutamine or not, patients were categorized as the dobutamine group or non dobutamine group.We used propensity score matched (PSM) analysis to adjust for confoundings. The primary outcome was hospital mortality.ResultsIn the present study, after screening 38,605 patients, 2826 patients with sepsis were included. 121 patients were in dobutamine group and 2165 patients were in non dobutamine group. Compared with patients in non-dobutamine group, patients in dobutamine group had a lower MAP, higher HR, higher RR, higher severity of illness scores. 72 of 121 patients (59.5%) in the dobutamine group and 754 of 2165 patients (34.8%) in the non-dobutamine group died in the hospital, which resulted in a significant between-group difference (OR 1.56, 95% CI 1.01–2.40; P = 0.000). For the secondary outcomes, patients in dobutamine group received more MV use, more renal replacement therapy use, had longer ICU stay durations and more cardiac arrhythmias than those in non-dobutamine group. After adjusting for confoundings between groups by PSM analysis, hospital mortality was consistently higher in dobutamine group than that in non-dobutamine group (60.2% vs. 49.4%, OR 1.55, 95% CI 1.01–2.37; P = 0.044).ConclusionsAmong patients with sepsis, our study showed that the use of dobutamine was not associated with decreased hospital mortality. Further large scale, randomized controlled studies are warrented to confirm our findings.

Asociación entre temperatura corporal al ingreso a urgencias y mortalidad intrahospitalaria en pacientes sépticos, estudio de cohortes

ObjectiveTo estimate the relationship between body temperature on admission and hospital mortality. DesignProspective analytical observational cohort study conducted between February and July 2017 on patients diagnosed with sepsis, and who were admitted to fourth level hospital. Digital temperature was taken, and the outcome was in-hospital mortality. FrameworkThe association between body temperature and hospital mortality in sepsis is controversial. Studies show that fever increases oxygen consumption and worsens multi-organ dysfunction, and the counterpart is, that it helps control pathogens. PatientsPatients admitted consecutively over a 6-month period to the Resuscitation room of Méderi Hospital Universitario Mayor with sepsis and met the inclusion and exclusion criteria. Interventions and measurementsThe axillary digital temperature was taken upon admission, using a standardised digital thermometer, guaranteed and with a calibration guarantee). ResultsThe relative risk for in-hospital mortality in septic patients, according to hypothermia vs no-hypothermia was 1.58, 95%, confidence interval 0.85-2.84, P=.056. The incidence of death in hypothermic patients was 4.2 per 100 hospital admission days, compared to an incidence of death in non-hypothermic patients of 2.6 per 100 patient hospital admission days. This was not statistically significant (P=.056). ConclusionsAlthough there is a non-statistically significant trend between presenting with hypothermia and mortality, there was no direct association in this cohort between body temperature and in-hospital mortality. In this population, the factors most associated with in-hospital mortality were pulmonary foci and septic shock.

Preadmission Antihypertensive Drug Use and Sepsis Outcome: Impact of Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs)

Several studies have reported improved sepsis outcomes when certain preadmission antihypertensive drugs, namely, calcium channel blockers (CCBs), are used. This study aims to determine whether preadmission antihypertensive drug use, especially angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), is associated with decreased total hospital mortality in sepsis. This study was conducted using the unique database of a sepsis cohort from the National Health Insurance Research Database in Taiwan. Frequency matching for age and sex between preadmission antihypertensive drug users (study cohort) and nonusers (comparison cohort) was conducted. The primary outcome was total hospital mortality. Logistic regression analyses were performed to calculate the odds ratios (ORs) of important variables. Further joint effect analyses were carried out to examine the impacts of different combinations of antihypertensive drugs. A total of 33,213 sepsis antihypertensive drug use patients were retrieved as the study cohort, and an equal number of matched sepsis patients who did not use antihypertensive drugs were identified as the comparison cohort. The study cohort had a higher incidence rate of being diagnosed with septic shock compared with the comparison cohort (4.36%-2.31%, P < 0.001) and a higher rate of total hospital mortality (38.42%-24.57%, P < 0.001). In the septic shock condition, preadmission antihypertensive drug use was associated with a decreased adjusted OR (OR = 0.66, 95% confidence interval [CI], 0.55-0.80) for total hospital mortality, which was not observed for the nonseptic shock condition. Compared with antihypertensive drug nonusers, both ACEI and ARB users had decreased adjusted ORs for total hospital mortality in sepsis (adjusted OR = 0.93, 95% CI, 0.88-0.98 and adjusted OR = 0.85, 95% CI, 0.81-0.90); however, CCB, beta-blocker, and diuretic users did not. In the septic shock condition, ACEI, ARB, CCB, and beta-blocker users all had decreased ORs for total hospital mortality. Joint effect analysis showed ACEI use, except in combination with diuretics, to be associated with a decreased adjusted OR for total hospital mortality in sepsis. Similar results were observed for ARB users. Preadmission ACEI or ARB use is associated with a decreased risk of total hospital mortality, regardless of a nonshock or septic shock condition.

A risk-model for hospital mortality among patients with severe sepsis or septic shock based on German national administrative claims data.

BackgroundSepsis is a major cause of preventable deaths in hospitals. Feasible and valid methods for comparing quality of sepsis care between hospitals are needed. The aim of this study was to develop a risk-adjustment model suitable for comparing sepsis-related mortality between German hospitals.MethodsWe developed a risk-model using national German claims data. Since these data are available with a time-lag of 1.5 years only, the stability of the model across time was investigated. The model was derived from inpatient cases with severe sepsis or septic shock treated in 2013 using logistic regression with backward selection and generalized estimating equations to correct for clustering. It was validated among cases treated in 2015. Finally, the model development was repeated in 2015. To investigate secular changes, the risk-adjusted trajectory of mortality across the years 2010–2015 was analyzed.ResultsThe 2013 deviation sample consisted of 113,750 cases; the 2015 validation sample consisted of 134,851 cases. The model developed in 2013 showed good validity regarding discrimination (AUC = 0.74), calibration (observed mortality in 1st and 10th risk-decile: 11%-78%), and fit (R2 = 0.16). Validity remained stable when the model was applied to 2015 (AUC = 0.74, 1st and 10th risk-decile: 10%-77%, R2 = 0.17). There was no indication of overfitting of the model. The final model developed in year 2015 contained 40 risk-factors. Between 2010 and 2015 hospital mortality in sepsis decreased from 48% to 42%. Adjusted for risk-factors the trajectory of decrease was still significant.ConclusionsThe risk-model shows good predictive validity and stability across time. The model is suitable to be used as an external algorithm for comparing risk-adjusted sepsis mortality among German hospitals or regions based on administrative claims data, but secular changes need to be taken into account when interpreting risk-adjusted mortality.

Reply: The Timing of Early Antibiotics and Hospital Mortality in Sepsis: Playing Devil's Advocate.

Reply: The Timing of Early Antibiotics and Hospital Mortality in Sepsis: Playing Devil's Advocate.

The Timing of Early Antibiotics and Hospital Mortality in Sepsis: Playing Devil's Advocate.

The Timing of Early Antibiotics and Hospital Mortality in Sepsis: Playing Devil's Advocate.

The Timing of Early Antibiotics and Hospital Mortality in Sepsis.

Prior sepsis studies evaluating antibiotic timing have shown mixed results. To evaluate the association between antibiotic timing and mortality among patients with sepsis receiving antibiotics within 6 hours of emergency department registration. Retrospective study of 35,000 randomly selected inpatients with sepsis treated at 21 emergency departments between 2010 and 2013 in Northern California. The primary exposure was antibiotics given within 6 hours of emergency department registration. The primary outcome was adjusted in-hospital mortality. We used detailed physiologic data to quantify severity of illness within 1 hour of registration and logistic regression to estimate the odds of hospital mortality based on antibiotic timing and patient factors. The median time to antibiotic administration was 2.1 hours (interquartile range, 1.4-3.1 h). The adjusted odds ratio for hospital mortality based on each hour of delay in antibiotics after registration was 1.09 (95% confidence interval [CI], 1.05-1.13) for each elapsed hour between registration and antibiotic administration. The increase in absolute mortality associated with an hour's delay in antibiotic administration was 0.3% (95% CI, 0.01-0.6%; P = 0.04) for sepsis, 0.4% (95% CI, 0.1-0.8%; P = 0.02) for severe sepsis, and 1.8% (95% CI, 0.8-3.0%; P = 0.001) for shock. In a large, contemporary, and multicenter sample of patients with sepsis in the emergency department, hourly delays in antibiotic administration were associated with increased odds of hospital mortality even among patients who received antibiotics within 6 hours. The odds increased within each sepsis severity strata, and the increased odds of mortality were greatest in septic shock.

Long-term mortality after community-acquired sepsis: a longitudinal population-based cohort study

ObjectivePrior studies have concentrated on the acute short-term outcomes of sepsis, with little focus on its long-term consequences. The objective of this study was to characterise long-term mortality following a...

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Introduction: Sepsis is a morbid cause of hospitalization, however, little is known about the relative proportion of hospital deaths that result from sepsis. We evaluated a multi-center sample of hospitalizations at 21 community medical centers in the Kaiser Permanente Northern California integrated healthcare delivery system between September 2010 and September 2012 to determine the proportion of all hospital deaths associated with sepsis. Methods: We retrospectively analyzed all hospitalizations that included non-obstetrical patients aged ≥18 years with overnight stays (or death at any time). We identified sepsis patients based on diagnosis coding and manually-collected data from regional sepsis quality improvement (QI) initiatives. We used QI data-available for 83.9% of sepsis patients-to categorize patients based on sepsis severity and their eligibility for, or use of, early goal-directed therapy (EGDT). Results: Over two years, a total of 345,264 patients met the study criteria including 42,457 (12.3%) hospitalized for sepsis-85.7% with the 038 ICD-9 diagnosis code. Mean age was 69.5 ± 16.9 for sepsis patients and 64.1 ± 17.5 years for others. Sepsis patients had higher comorbid disease burden, acute severity of illness, and predicted mortality (9.3% ± 12.6% versus 2.4% ± 5.5%, p<0.001) when compared with non-sepsis patients. They also had higher ICU utilization (31.8% versus 13.5%) and length of stay (6.7 versus 3.8 days) than other inpatients. Sepsis hospital mortality was 10.5%; 30-day mortality was 15.2%. Hospital mortality otherwise was 1.9%. More than 43% (n = 4,463) of all inpatient deaths were among sepsis patients. Most had sepsis present on admission (93.8%) and nearly 40% had severe sepsis or septic shock. Hospital mortality varied by severity strata; for example, 6.6% of patients with non-severe sepsis died compared with 17.8% of patients receiving EGDT. Hospital mortality was 26.2% to 33.6% among EGDT-eligible patients who did not receive EGDT (either based on clinician judgment, contraindications, patient refusal, or comfort care status). In terms of all sepsis deaths, each sepsis strata (non-severe sepsis, sepsis with intermediate lactate, and EGDT-eligible sepsis) contributed roughly equal numbers of deaths. This included 1,225 (31.9%) deaths among non-severe, 1,213 (31.6%) among intermediate lactate, and 1,397 (36.4%) among EGDT-eligible sepsis patients. Conclusions: In a multi-center study of community hospitals, >43% of patients dying in the hospital had sepsis. These sepsis deaths were roughly equally distributed across severity strata.

Incidence, risk factors, and impact on mortality of status epilepticus in sepsis in the United States

We sought to determine the epidemiology of status epilepticus (SE), prevalence of risk factors and impact on hospital mortality in sepsis in the United States. We hypothesized that SE would be associated with increased mortality.