High Mortality in Severe Sepsis and Septic Shock Patients with Do-Not-Resuscitate Orders in East Asia

<div><p>Background</p><p>Severe sepsis is a potentially deadly illness and always requires intensive care. Do-not-resuscitate (DNR) orders remain a debated issue in critical care and limited data exist about its impact on care of septic patients, particularly in East Asia. We sought to assess outcome of severe sepsis patients with regard to DNR status in Taiwan.</p><p>Methods</p><p>A retrospective cohort study was conducted in intensive care units (ICUs) between 2008 and 2010. All severe sepsis patients were included for analysis. Primary outcome was association between DNR orders and ICU mortality. Volume of interventions was used as proxy indicator to indicate aggressiveness of care.</p><p>Results</p><p>Sixty-seven (9.4%) of 712 patients had DNR orders on ICU admission, and these patients were older and had higher disease severity compared with patients without DNR orders. Notably, DNR patients experienced high ICU mortality (90%). Multivariate analysis revealed that the presence of DNR orders was independently associated with ICU mortality (odds ratio: 6.13; 95% confidence interval: 2.66–14.10). In propensity score-matched cohort, ICU mortality rate (91%) in the DNR group was statistically higher than that (62%) in the non-DNR group (p <0.001). Regarding ICU interventions, arterial and central venous catheterization were more commonly used in DNR patients than in non-DNR patients.</p><p>Conclusions</p><p>From the Asian perspective, septic patients placed on DNR orders on ICU admission had exceptionally high mortality. In contrast to Western reports, DNR patients received more ICU interventions, reflecting more aggressive approach to dealing with this patient population. The findings in some ways reflect differences between East and West cultures and suggest that DNR status is an important confounder in ICU studies involving severely septic patients.</p></div

Patient characteristics with regard to the do-not-resuscitate status.

<p>Patient characteristics with regard to the do-not-resuscitate status.</p

Characteristics of propensity score-matched cohort.

<p>Characteristics of propensity score-matched cohort.</p

Multivariate logistic regression analysis to identify independent predictors of intensive care unit mortality.

<p>Multivariate logistic regression analysis to identify independent predictors of intensive care unit mortality.</p

Conditional effect plot of the estimated risk for in-hospital mortality against SOFA score upon admission, stratified by AKIN stage with the values of all other factors fixed.

<p>The risk of in-hospital mortality was the highest among patients in AKIN stage 3 with a high SOFA score.</p

In A, the inverse relation between <i>Q</i>_max and <i>R_p</i> is noted after pooling the data of all the groups (<i>Q</i>_max = 47.7300−0.2064× <i>R_p</i> and <i>r</i> = 0.2909; <i>p</i><0.005).

<p>However, the significant inverse linear correlation between the two parameters is predominantly derived from the data of the DM and DM+OXF groups (<i>Q</i>_max = 50.9368−0.3126× <i>R_p</i> and <i>r</i> = 0.4390; <i>p</i><0.05 in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0069977#pone-0069977-g004" target="_blank">Figure 4B</a>). NC, normal controls; NC+ALC, NC treated with ALC; NC+OXF, NC treated with OXF; DM, STZ-induced diabetic rats; DM+ALC, DM treated with ALC; DM+OXF, DM treated with OXF; ALC, acetyl-L-carnitine; OXF, oxfenicine; <i>Q</i>_max, the theoretical maximum flow; <i>R_p</i>, the total peripheral resistance.</p

Clinical features of admitted nonagenarians by length of hospital stay (percentage in parentheses).

*<p>All continuous variables were expressed in mean ± standard deviation, while dichotomized variables were expressed in frequency and percentages.</p>$<p>Including oncologic or endocrinologic illnesses.</p><p>Abbreviations: CAD, coronary artery disease; AMI, acute myocardial infarction; HF, heart failure; PAOD, peripheral artery occlusive disease; PUD, peptic ulcer disease; COPD, chronic obstructive pulmonary disease; CVA, cerebrovascular accident; CKD, chronic kidney disease; AE, acute exacerbation; UGI, upper gastrointestinal tract; LGI, lower gastrointestinal tract; UTI, urinary tract infection; AKI, acute kidney injury.</p

Kaplan-Meier survival curve based on category of main admission diagnosis (nephrologic vs. non-nephrologic diseases).

<p>Nephrologic diseases included the diagnosis or management of diseases comprised of acute/chronic renal dysfunction, urinary tract infection (upper/lower), and dyselectrolytemia.</p

The solid lines of A and B show the measured ascending aortic flow signal and the LV pressure waveform, respectively, of one control rat.

<p>In Graph B, the dashed line represents the isovolumic pressure curve at an end-diastolic volume, which is estimated by fitting a sinusoidal function to the isovolumic portions of the measured LV pressure. Graphs C and D show the measured data and model-generated data when the elastance-resistance model is fit over <i>t_ej</i><<i>t</i><<i>t_piso</i>_max; <i>t_ej</i> is the onset of ventricular ejection and <i>t_piso</i>_max is the time of peak isovolumic pressure. In Graph C, the solid line represents measured data, and dashed lines represent model-derived data. In Graph D, the dashed line has the slope of regression that equals 1.0. The solid line represents the relation between the measured and model-generated data. <i>P</i>(<i>t</i>) is the measured LV pressure; <i>P_iso</i>(<i>t</i>) is the estimated isovolumic pressure; <i>P</i>(<i>t</i>)/<i>P_iso</i>(<i>t</i>) is the ratio of <i>P</i>(<i>t</i>) to <i>P_iso</i>(<i>t</i>).</p

Acute Kidney Injury Network classification of acute kidney injury.

<p>Acute kidney injury defined as an abrupt reduction in kidney function within 48 hours.</p><p>Individuals who receive renal replacement therapy are considered to have met the criteria for stage 3.</p