Effects of Inotropes on the Mortality in Patients With Septic Shock

Background: Although surviving sepsis campaign guidelines recommend the use of inotropes in the presence of myocardial dysfunction, the effects of inotropes, including epinephrine, dobutamine, and milrinone, on in-hospital mortality in patients with septic shock remains unclear. Materials and Methods: We conducted an international,2-center, retrospective cohort study. The Cox proportional hazards regression model with time-varying covariates was used to investigate whether epinephrine, milrinone, or dobutamine reduces in-hospital mortality in patients with septic shock. Sensitivity analysis was performed using propensity score matching. The primary outcome was in-hospital mortality. The secondary outcome included atrial fibrillation (Afib) with a rapid ventricular response (RVR) in the intensive care unit (ICU) and ICU-free days. Results: A total of 417 patients with septic shock were included, 72 (17.3%) of whom received inotropes. The use of epinephrine and dobutamine was associated with significantly higher in-hospital mortality (epinephrine, hazard ratio [HR]: 4.79, 95% confidence interval [CI]: 2.12-10.82, P = .001; dobutamine, HR: 2.53, 95% CI: 1.30-4.95, P = .046). The effects of epinephrine and dobutamine were time- and dose-dependent. The use of milrinone was not associated with increased mortality (HR: 1.07, 95% CI: 0.42-2.68, P = .345). The use of epinephrine, dobutamine, and milrinone was associated with significantly increased odds of Afib with RVR (epinephrine, odds ratio [OR]: 3.88, 95% CI: 1.11-13.61, P = .034; dobutamine, OR: 3.95, 95% CI: 1.14-13.76; and milrinone, OR: 3.77, 95% CI: 1.05-13.59). On the other hand, the use of epinephrine, dobutamine, and milrinone was not associated with less ICU-free days (epinephrine, adjusted OR: 0.30, 95% CI: 0.09-1.01, P = .053; dobutamine, adjusted OR: 0.91, 95% CI: 0.29-2.84; and milrinone, adjusted OR: 0.60, 95% CI: 0.19-1.87). Conclusion: The present study showed that the use of epinephrine and dobutamine was associated with significantly increased in-hospital mortality in patients with septic shock. These effects were both time- and dose-dependent. On the other hand, the use of milrinone was not associated with increased in-hospital mortality.

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Quantitative assessment of erector spinae muscles and prognosis in elderly patients with pneumonia

Scientific Reports ◽

10.1038/s41598-021-83995-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hiroki Yoshikawa ◽

Kosaku Komiya ◽

Takashi Yamamoto ◽

Naoko Fujita ◽

Hiroaki Oka ◽

...

Keyword(s):

Elderly Patients ◽

Hospital Mortality ◽

Regression Models ◽

Proportional Hazards ◽

Community Acquired Pneumonia ◽

Cox Proportional Hazards ◽

Erector Spinae ◽

Cross Sectional ◽

Proportional Hazards Regression ◽

Survivor Group

AbstractErector spinae muscle (ESM) size has been reported as a predictor of prognosis in patients with some respiratory diseases. This study aimed to assess the association of ESM size on all-cause in-hospital mortality among elderly patients with pneumonia. We retrospectively included patients (age: ≥ 65 years) admitted to hospital from January 2015 to December 2017 for community-acquired pneumonia who underwent chest computed tomography (CT) on admission. The cross-sectional area of the ESM (ESMcsa) was measured on a single-slice CT image at the end of the 12th thoracic vertebra and adjusted by body surface area (BSA). Cox proportional hazards regression models were used to assess the influence of ESMcsa/BSA on in-hospital mortality. Among 736 patients who were admitted for pneumonia, 702 patients (95%) underwent chest CT. Of those, 689 patients (98%) for whom height and weight were measured to calculate BSA were included in this study. Patients in the non-survivor group were significantly older, had a greater frequency of respiratory failure, loss of consciousness, lower body mass index, hemoglobin, albumin, and ESMcsa/BSA. Multivariate analysis showed that a lower ESMcsa/BSA independently predicted in-hospital mortality after adjusting for these variables. In elderly patients with pneumonia, quantification of ESMcsa/BSA may be associated with in-hospital mortality.

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Abstract 3248: Is It Safe to Train Residents to Perform Cardiac Surgery? Intermediate Term Follow-up

Circulation ◽

10.1161/circ.116.suppl_16.ii_730-c ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Billie Jean Martin ◽

Dimitri Kalavrouziotis ◽

Roger Baskett

Keyword(s):

Cardiac Surgery ◽

Hospital Mortality ◽

Proportional Hazards ◽

Artery Bypass ◽

Cox Proportional Hazards ◽

Adverse Outcomes ◽

Short Term ◽

Term Outcome ◽

Teaching Case ◽

Teaching Cases

Introduction While there are rigourous assessments made of trainees’ knowledge through formal examinations, objective assessments of technical skills are not available. Little is known about the safety of allowing resident trainees to perform cardiac surgical operations. Methods Peri-operative date was prospectively collected on all patients who underwent coronary artery bypass grafting (CABG), aortic valve replacement (AVR) or a combined procedure between 1998 and 2005. Teaching-cases were identified by resident records and defined as cases which the resident performed skin to skin. Pre-operative characteristics were compared between teaching and non-teaching cases. Short-term adverse events were defined as a composite of: in-hospital mortality, stroke, intra- or post-operative intra-aortic balloon pump (IABP) insertion, myocardial infarction, renal failure, wound infection, sepsis or return to the operating room. Intermediate adverse outcomes were defined as hospital readmission for any cardiac disease or late mortality. Logistic regression and Cox proportional hazard models were used to adjust for differences in age, acuity, and medical co-morbidities. Outcomes were compared between teaching and non-teaching cases. Results 6929 cases were included, 895 of which were identified as teaching-cases. Teaching-cases were more likely to have an EF<40%, pre-operative IABP, CHF, combined CABG/AVRs or total arterial grafting cases (all p<0.01). However, a case being a teaching-case was not a predictor of in-hospital mortality (OR=1.02, 95%CI 0.67–1.55) or the composite short-term outcome (OR=0.97, 95%CI 0.75–1.24). The Kaplan-Meier event-free survival of staff and teaching-cases was equivalent at 1, 3, and 5 years: 80% vs. 78%, 67% vs. 66%, and 58% vs. 55% (log-rank p=0.06). Cox proportional hazards regression modeling did not demonstrate teaching-case to be a predictor of late death or re-hospitalization (HR=1.05, 95%CI 0.94 –1.18). Conclusions Teaching-cases were more likely to have greater acuity and complexity than non-teaching cases. Despite this, teaching cases did no worse than staff cases in the short or intermediate term. Allowing residents to perform cardiac surgery does not appear to adversely affect patient outcomes.

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Epidemiology, Risk Factors, and Outcomes After Early Posttransplant Clostridiodes difficile Infection in Renal Transplant Recipients

Annals of Pharmacotherapy ◽

10.1177/1060028019845003 ◽

2019 ◽

Vol 53 (10) ◽

pp. 1020-1025

Author(s):

Margaret R. Jorgenson ◽

Jillian L. Descourouez ◽

Dou-Yan Yang ◽

Glen E. Leverson ◽

Christopher M. Saddler ◽

...

Keyword(s):

Risk Factors ◽

Renal Transplant ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Female Gender ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Secondary Outcome ◽

Induction Agent ◽

Renal Transplant Recipients

Background: Modifiable risk-factors associated with Clostridioides difficile infection (CDI) in renal-transplant (RTX) have not been clearly established and peri-transplant risk has not been described. Objective: Evaluate epidemiology, risk-factors and outcomes after CDI occurring in the first 90 days after RTX (CDI-90).Methods: Observational cohort study/survival analysis of adult RTX recipients from 1/1/2012-12/31/2015. Primary outcome was CDI-90 incidence/risk-factors. Secondary outcome was evaluation of post-90 day transplant outcomes. Results: 982 patients met inclusion criteria; 46 with CDI-90 and 936 without (comparator). CDI incidence in the total population was 4.7% at 90 days, 6.3% at 1 year, and 6.4% at 3 years. Incidence of CDI-90 was 5%; time to diagnosis was 19.4±25 days (median 7). Risk-factors for CDI-90 were alemtuzumab induction (Hazard ratio [HR] 1.5, 95% CI(1.1-2.0), p = 0.005) and age at transplant (HR 1.007/year, 95% CI (1.002-1.012), p= 0.007). However, risk-factors for CDI at any time were different; donation-after-circulatory-death (DCD) donor (HR 2.5 95% CI (1.3-4.9), p = 0.008) and female gender (HR 1.6 95% CI (1.0-2.7), p = 0.049). On Kaplan-Meier, CDI-90 appeared to have an impact on patient/graft survival, however when analyzed in a multivariable stepwise Cox proportional hazards model, only age was significantly associated with survival ( p = 0.002). Conclusion and Relevance: Incidence of CDI-90 is low, mostly occurring in the first post-operative month. Risk-factors vary temporally based on time from transplant. In the early post-op period induction agent and age at transplant are significant, but not after. Associations between CDI and negative graft outcomes appear to be largely driven by age. Future studies validating these risk-factors as well as targeted prophylaxis strategies and their effect on long term graft outcomes and the host microbiome are needed.

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Osteoprotegerin is Higher in Sepsis Than in Noninfectious SIRS and Predicts 30-Day Mortality of SIRS Patients in the Intensive Care

The Journal of Applied Laboratory Medicine ◽

10.1373/jalm.2018.026559 ◽

2019 ◽

Vol 3 (4) ◽

pp. 559-568 ◽

Cited By ~ 1

Author(s):

Hans Kemperman ◽

Irene T Schrijver ◽

Mark Roest ◽

Jozef Kesecioglu ◽

Wouter W van Solinge ◽

...

Keyword(s):

Septic Shock ◽

Intensive Care ◽

Complex Disease ◽

Proportional Hazards ◽

Vascular System ◽

Cox Proportional Hazards ◽

Admission Data ◽

Increased Risk ◽

Severity Of The Disease ◽

Sepsis And Septic Shock

AbstractBackgroundSystemic inflammatory response syndrome (SIRS) is a complex disease involving multiple pathways and organs. Biomarkers reflecting these pathways and organ function could correlate with the severity of the disease. Osteoprotegerin (OPG), mainly known for its role in bone metabolism, is also involved in the immune and vascular system and is therefore an interesting biomarker to study in SIRS patients. In this prospective observational study, we investigated the correlation of plasma OPG concentrations, sepsis, and 30-day mortality of SIRS patients in the intensive care unit (ICU).MethodsThis observational, single-center, cohort study included 313 consecutive patients admitted to the ICU, with an anticipated stay of more than 48 h and SIRS on admission. Data from included patients were collected daily until discharge or death for a maximum of 10 days. Thirty-day mortality was retrospectively assessed. OPG concentrations were measured in the first 48 h after admission. The relation of OPG with no sepsis, sepsis, and septic shock was assessed with the Kruskal–Wallis test and the Mann–Whitney U-test. Cox proportional hazards regression was used to study OPG concentrations and 30-day mortality.ResultsOPG concentrations were higher in patients with sepsis and septic shock than in patients without sepsis. Furthermore, patients with OPG concentrations in the highest tertile at admission in the ICU have an increased risk of mortality within 30 days when compared to patients with OPG concentrations in the lowest and middle tertiles, independent of acute physiologic and chronic health evaluation (APACHE) and sequential organ failure assessment (SOFA) scores.ConclusionsWe show that OPG is a biomarker that correlates with sepsis and predicts mortality of SIRS patients in the ICU.

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Simulating Duration Data for the Cox Model

Political Science Research and Methods ◽

10.1017/psrm.2018.19 ◽

2018 ◽

Vol 7 (04) ◽

pp. 921-928 ◽

Cited By ~ 2

Author(s):

Jeffrey J. Harden ◽

Jonathan Kropko

Keyword(s):

Hazard Function ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Simulation Studies ◽

Baseline Hazard ◽

Baseline Hazard Function ◽

Time Varying Covariates

The Cox proportional hazards model is a popular method for duration analysis that is frequently the subject of simulation studies. However, no standard method exists for simulating durations directly from its data generating process because it does not assume a distributional form for the baseline hazard function. Instead, simulation studies typically rely on parametric survival distributions, which contradicts the primary motivation for employing the Cox model. We propose a method that generates a baseline hazard function at random by fitting a cubic spline to randomly drawn points. Durations drawn from this function match the Cox model’s inherent flexibility and improve the simulation’s generalizability. The method can be extended to include time-varying covariates and non-proportional hazards.

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Sodium Fluctuations and Mortality in a General Hospitalized Population

Kidney & Blood Pressure Research ◽

10.1159/000500916 ◽

2019 ◽

Vol 44 (4) ◽

pp. 604-614 ◽

Cited By ~ 3

Author(s):

Gianmarco Lombardi ◽

Pietro Manuel Ferraro ◽

Luca Calvaruso ◽

Alessandro Naticchia ◽

Silvia D’Alonzo ◽

...

Keyword(s):

Hospital Mortality ◽

Hospital Admission ◽

Hospital Stay ◽

Proportional Hazards ◽

Medical Center ◽

Cerebrovascular Diseases ◽

Linear Increase ◽

Cox Proportional Hazards ◽

Hospital Death ◽

Cox Proportional Hazards Models

Background/Aims: Aim of our study was to describe the association between natremia (Na) fluctuation and hospital mortality in a general population admitted to a tertiary medical center. Methods: We performed a retrospective observational cohort study on the patient population admitted to the Fondazione Policlinico A. Gemelli IRCCS Hospital between January 2010 and December 2014 with inclusion of adult patients with at least 2 Na values available and with a normonatremic condition at hospital admission. Patients were categorized according to all Na values recorded during hospital stay in the following groups: normonatremia, hyponatremia, hypernatremia, and mixed dysnatremia. The difference between the highest or the lowest Na value reached during hospital stay and the Na value read at hospital admission was used to identify the maximum Na fluctuation. Cox proportional hazards models were used to estimate hazard ratios (HRs) for in-hospital death in the groups with dysnatremias and across quartiles of Na fluctuation. Covariates assessed were age, sex, highest and lowest Na level, Charlson/Deyo score, cardiovascular diseases, cerebrovascular diseases, dementia, congestive heart failure, severe kidney disease, estimated glomerular filtration rate, and number of Na measurements during hospital stay. Results: 46,634 admissions matched inclusion criteria. Incident dysnatremia was independently associated with in-hospital mortality (hyponatremia: HR 3.11, 95% CI 2.53, 3.84, p < 0.001; hypernatremia: HR 5.12, 95% CI 3.94, 6.65, p < 0.001; mixed-dysnatremia: HR 4.94, 95% CI 3.08, 7.92, p < 0.001). We found a higher risk of in-hospital death by linear increase of quartile of Na fluctuation (p trend <0.001) irrespective of severity of dysnatremia (HR 2.34, 95% CI 1.55, 3.54, p < 0.001, for the highest quartile of Na fluctuation compared with the lowest). Conclusions: Incident dysnatremia is associated with higher hospital mortality. Fluctuation of Na during hospital stay is a prognostic marker for hospital death independent of dysnatremia severity.

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Arbutin Content and Tyrosinase Activity of Bergenia Extracts

Natural Product Communications ◽

10.1177/1934578x1701200422 ◽

2017 ◽

Vol 12 (4) ◽

pp. 1934578X1701200 ◽

Cited By ~ 1

Author(s):

Lenka Tůmová ◽

Iva Dolečková ◽

Helena Hendrychová ◽

Marie Kašparová

Keyword(s):

Tyrosinase Activity ◽

The Other ◽

Aqueous Extracts ◽

Other Hand ◽

Ethanol Extracts ◽

Dose Dependent Increase ◽

Dose Dependent ◽

Diphenolase Activity

The total arbutin content in the leaves of all the studied Bergenia plants ( B. crassifolia, B. ciliata and B. x ornata) was determined. The highest values of the arbutin content have been established for B. crassifolia (58.9 ± 0.7 mg.g−1 DW) and B. x ornata (51.0 ± 1.21 mg.g−1 DW), and the lowest for B. ciliata (5.9 ± 0.6 mg.g−1 DW). Arbutin concentration in the Bergenia leaves was the lowest in spring, in the autumn, on the contrary it increased. All the tested aqueous extracts caused a dose-dependent increase in diphenolase activity of fungal tyrosinase in a similar way as arbutin. On the other hand, all the ethanol extracts inhibited the diphenolase activity of tyrosinase.

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Influence of adenosine triphosphate on the isolated perfused mesenteric artery of the rabbit

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y83-201 ◽

1983 ◽

Vol 61 (11) ◽

pp. 1409-1417 ◽

Cited By ~ 13

Author(s):

V. S. R. Krishnamurty ◽

P. J. Kadowitz

Keyword(s):

Adenosine Triphosphate ◽

Mesenteric Arteries ◽

The Other ◽

Receptor Blocker ◽

Medium Size ◽

Inhibitory Influence ◽

Vasodilator Response ◽

Other Hand ◽

Vasoconstrictor Response ◽

Dose Dependent

The vascular effects of adenosine triphosphate (ATP) were examined in the isolated perfused mesenteric arteries of the rabbit. Bolus injections of ATP (1 × 10−8 to 10−6 mol) induced a dose-dependent vasoconstrictor response at resting perfusion pressure, while continuous perfusion with ATP briefly elicited a vasoconstrictor response which was not maintained. Perfusion with phentolamine (2.65 × 10−6 M, an α-adrenergic receptor blocker), indomethacin (8.37 × 10−6 M, an inhibitor of cyclooxygenase), atropine (1 × 10−7 M, a muscarinic receptor blocker), and hydralazine (2 × 10−4 M, a vascular smooth muscle inhibitor) for a period of 1 h had no effect on vasoconstrictor responses to ATP. However, pretreatment with reserpine (2 mg∙kg−1∙day−1 for 2 days), an agent which depletes catecholamines, potentiated responses to ATP. On the other hand, when vascular tone was increased with an isoosmotic 60 mM K+ depolarizing Krebs bicarbonate solution, bolus injections of ATP elicited a prominent dose-dependent vasoconstriction followed by a prominent vasodilation. The degree of vasodilation but not of vasoconstriction elicited by ATP was greater in small terminal arteries with branches (<0.5 mm outside diameter (o.d.)) than in the medium size arteries (≤1 mm o.d.) without terminal branches. Both the vasoconstrictor and vasodilator responses were unaffected by a perfusion with atropine, indomethacin, or eicosatetraynoic acid (ETYA, 1 × 10−4 M) for 1 – 2 h. The vasoconstrictor responses were potentiated while the vasodilator responses were inhibited significantly by perfusion with propranolol (3 × 10−6 M) and phentolamine (2.65 × 10−6 M) together for 1 h or by pretreatment with reserpine followed by cold storage at 2 °C for 24 h. Perfusion with 8-phenyltheophylline (4 × 10−6 M (8-PT), an adenosine receptor blocker) for 1 h significantly inhibited by the vasodilator responses to bolus injections of adenosine but not to ATP. Further, ATP but not adenosine elicited a much more prominent vasodilator response on norepinephrine (NE) induced tone than on 60 mM K+. These studies suggest that ATP may induce vasoconstriction independent of activation of α-adrenergic or muscarinic receptors or enhanced synthesis of prostaglandins. This vasoconstriction is resistant to the inhibitory influence of hydralazine. On the other hand, the vasodilator response to ATP may be mediated through its interactions with released or circulating norepinephrine.

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Propensity-Based Study of Aminoglycoside Nephrotoxicity in Patients with Severe Sepsis or Septic Shock

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.03750-14 ◽

2014 ◽

Vol 58 (12) ◽

pp. 7468-7474 ◽

Cited By ~ 26

Author(s):

W. Picard ◽

F. Bazin ◽

B. Clouzeau ◽

H.-N. Bui ◽

M. Soulat ◽

...

Keyword(s):

Septic Shock ◽

Renal Failure ◽

Regression Analysis ◽

Severe Sepsis ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Adjusted Relative Risk ◽

Cox Proportional Hazards Regression ◽

Proportional Hazards Regression ◽

Increased Risk

ABSTRACTTo assess the risk of acute kidney injury (AKI) attributable to aminoglycosides (AGs) in patients with severe sepsis or septic shock, we performed a retrospective cohort study in one medical intensive care unit (ICU) in France. Patients admitted for severe sepsis/septic shock between November 2008 and January 2010 were eligible. A propensity score for AG administration was built using day 1 demographic and clinical characteristics. Patients still on the ICU on day 3 were included. Patients with renal failure before day 3 or endocarditis were excluded. The time window for assessment of renal risk was day 3 to day 15, defined according to the RIFLE (risk, injury, failure, loss, and end-stage renal disease) classification. The AKI risk was assessed by means of a propensity-adjusted Cox proportional hazards regression analysis. Of 317 consecutive patients, 198 received AGs. The SAPS II (simplified acute physiology score II) score and nosocomial origin of infection favored the use of AGs, whereas a preexisting renal insufficiency and the neurological site of infection decreased the propensity for AG treatment. One hundred three patients with renal failure before day 3 were excluded. AGs were given once daily over 2.6 ± 1.1 days. AKI occurred in 16.3% of patients in a median time of 6 (interquartile range, 5 to 10) days. After adjustment to the clinical course and exposure to other nephrotoxic agents between day 1 and day 3, a propensity-adjusted Cox proportional hazards regression analysis showed no increased risk of AKI in patients receiving AGs (adjusted relative risk = 0.75 [0.32 to 1.76]). In conclusion, in critically septic patients presenting without early renal failure, aminoglycoside therapy for less than 3 days was not associated with an increased risk of AKI.

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Chemotherapy-induced neutropenia as a prognostic factor in patients with unresectable pancreatic cancer treated with gemcitabine and nab-paclitaxel.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.324 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 324-324

Author(s):

Motoyasu Kan ◽

Hiroshi Imaoka ◽

Masafumi Ikeda ◽

Shuichi Mitsunaga ◽

Izumi Ohno ◽

...

Keyword(s):

Pancreatic Cancer ◽

Prognostic Factor ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Unresectable Pancreatic Cancer ◽

Who Grade ◽

Chemotherapy Induced Neutropenia ◽

Time Varying Covariates

324 Background: Chemotherapy-induced neutropenia (CIN) has been reported to be associated with a longer survival in patients with various cancers. The aim of our study was to assess whether CIN could also be a prognostic factor in patients with unresectable pancreatic cancer receiving treatment with gemcitabine (GEM) and nab-paclitaxel (nab-PTX). Methods: We retrospectively analyzed the medical records of pancreatic cancer patients who had been treated with GEM and nab-PTX as first-line chemotherapy. CIN was categorized on the basis of the worst WHO grade during chemotherapy: absent/mild (≦ grade 2), or severe (≧ grade 3). The background characteristics and CIN as time-varying covariates (TVCs) were analyzed as potential prognostic factors using a Cox proportional hazards model. Results: We analyzed a total of 291 patients (absent/mild CIN: 116 patients; severe CIN: 174 patients). The median time to severe CIN was 14 days (interquartile range: 10–39 days). The median overall survival (OS) was significantly longer in the severe CIN group than in the absent/mild CIN group (19.2 vs. 11.3 months; p < 0.001) After adjustments, severe CIN was identified as an independent predictor of the OS (HR, 0.54; 95% CI, 0.38–0.77; p = 0.001). In the TVC model also, severe CIN was identified as an independent factor (HR, 0.79; 95% CI, 0.68–0.92; p = 0.002). Conclusions: Severe CIN was associated with a longer survival in patients with pancreatic cancer treated with GEM and nab-PTX.

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