Clinical Examination for the Prediction of Mortality in the Critically Ill

The Simple Intensive Care Studies-I

Bart Hiemstra, MD; Ruben J. Eck, MD; Renske Wiersema, BSc; Thomas Kaufmann, MD; Geert Koster, MD; Thomas W.L. Scheeren, MD, PhD; Harold Snieder, PhD; Anders Perner, MD, PhD; Ville Pettilä, MD, PhD; Jørn Wetterslev, MD, PhD; Frederik Keus, MD, PhD; Iwan C.C. van der Horst, MD, PhD; SICS Study Group


Crit Care Med. 2019;47(10):1301-1309. 

In This Article


Patient Characteristic and Outcome

A total of 1,442 patients were assessed for eligibility between March 27, 2015, and July 22, 2017. The inclusion criteria were fulfilled in 1,212 patients, of whom 137 patients were not included for various reasons (Figure 1). In the final analysis, 1,075 patients (89%) were included. The median time from ICU admission to inclusion was 15 hours (IQR = 8–20 hr). The proportion of missing values per variable is presented in eTable 2 (Supplemental Digital Content 2, and per case (eFigure 2, Supplemental Digital Content 2, One third of the patients was admitted after acute or complicated surgery, and the most common admission diagnoses were of cardiovascular or respiratory origin (Table 1).

Figure 1.

Flow diagram of the SICS-I. CCUS = critical care ultrasonography, SICS = Simple Intensive Care Studies.

After 90 days, 298 patients (28%) had died and eight patients (1%) were lost from follow-up due to emigration to or residence in another country. Patients who died within 90 days were significantly older, were more often mechanically ventilated, had higher positive end-expiratory pressures and lower diastolic blood pressures and mean arterial pressures (p < 0.015; Table 2). Most clinical signs reflecting organ perfusion differed: patients who died had significantly lower urine outputs, colder extremities, longer CRTs, and more severe skin mottling during the clinical examination.

Clinical Examination and 90-day Mortality

Both unadjusted and age- and sex-adjusted analyses showed that most clinical examination findings were associated with 90-day mortality (eTable 3, Supplemental Digital Content 2, Multivariable logistic regression adjusted for age and norepinephrine infusion rate showed that five clinical examination findings, that is, higher respiratory rate, higher systolic blood pressure, lower central temperature, altered consciousness, and decreased urine output, were independently associated with 90-day mortality (Figure 2). The variables atrial fibrillation, diastolic blood pressure, and severe skin mottling were of suggestive statistical significance due to a p-value of greater than 0.015 and a statistical significance in less than 80 of the 100 bootstrap replications (Figure 2).

Figure 2.

Clinical examination findings associated with 90-day mortality. Five of the eight clinical examination findings in our model were independently associated with mortality (i.e., p < 0.015): respiratory rate, systolic blood pressure, central temperature, consciousness, and urine output. The model included all 1,075 patients of whom 298 died. Pseudo R 2 = 0.14. Hosmer–Lemeshow goodness of fit test χ 2 = 7.43; p = 0.68 (see plot in eFigure 2, Supplemental Digital Content 2, area under the receiver operating characteristic curves = 0.74 (95% CI, 0.71–0.78). Mottling was scored according to Ait-Oufella et al (19). DBP = diastolic blood pressure, SBP = systolic blood pressure.

The multivariable logistic regression analysis was repeated with systolic blood pressure in quartiles because this variable had a U-shaped relationship with mortality (eFigure 3, Supplemental Digital Content 2, In this model, only the highest quartile (i.e., a systolic blood pressure > 133 mm Hg) had a suggestive statistically significant association with mortality (OR = 1.65; 98.5% CI, 0.90–3.05; p = 0.046; eTable 4, Supplemental Digital Content 2, In the complete case analysis, all variables except diastolic blood pressure remained statistically significant (eTable 5, Supplemental Digital Content 2,

Performance of Clinical Examination When Compared With Prognostic Scores

When comparing AUC's to three established ICU prognostic risk scores, the clinical examination model was comparable to the SAPS-II and APACHE-IV and significantly better than the SOFA score (Figure 3). The clinical examination model distinguished 817 patients (76%) correctly into survivor or nonsurvivor. The number of patients correctly classified was 810 (75%) for the SAPS-II, 818 (76%) for the APACHE-IV, and 800 (74%) for the SOFA. The net reclassification improvement of the clinical examination model was 3.8% compared with the SAPS-II (p = 0.09), 5.0% compared with the APACHE-IV (p = 0.025), and 12% compared with the SOFA (p < 0.001).

Figure 3.

The discriminative value of the multivariable models to distinguish 90-day survivors from nonsurvivors using area under the receiver operating characteristic curves (AUC) analyses. Figure legend presents the AUC with 98.5% CI. The DeLong method was used to compare our clinical examination model to three prognostic scores commonly used in the intensive care. APACHE = Acute Physiology and Chronic Health Evaluation, SAPS = Simplified Acute Physiology Score, SOFA = Sequential Organ Failure Assessment.

Sensitivity Analysis: Clinical Examination and Short-term Mortality

The relation of clinical examination findings over time was studied using logistic regression analyses on 7- and 30-day mortalities and a Cox regression. Severe skin mottling had stronger associations with 7-day mortality (OR = 3.06; 95% CI, 1.34–6.98; p = 0.008) compared with 90-day mortality (OR = 2.45; 95% CI, 1.12–5.34; p = 0.025). Systolic and diastolic blood pressures were not statistically significantly associated with 7-day mortality (eTable 7, Supplemental Digital Content 2, Atrial fibrillation and diastolic blood pressures were not statistically significantly associated with 30-day mortality (eTable 7, Supplemental Digital Content 2, Results of the multivariable Cox regression were comparable to the logistic regression analysis used in the main analysis (eTable 8, Supplemental Digital Content 2,

Subgroup Analyses

In two predefined subgroup analyses, the patient population was stratified by vasopressor use and by underlying pathology. In these analyses, only the eight clinical examination findings that were statistically significant in the primary analysis were tested (eFigure 5, Supplemental Digital Content 2, In patients without vasopressors, only a higher respiratory rate and an altered consciousness had statistically significant associations with mortality (p < 0.001; eTable 9, Supplemental Digital Content 2, In patients receiving vasopressors, a higher respiratory rate, atrial fibrillation, lower central temperature, nonresponsiveness, decreased urine output, and severe skin mottling were independently associated with 90-day mortality (eTable 9, Supplemental Digital Content 2, In patients admitted with septic shock, only age and skin mottling over the knee were significantly associated with mortality (OR = 3.22; 95% CI, 1.31–7.94; p = 0.011). In the subgroups of patients admitted with acute liver failure or post-OLT, heart failure, with a CNS pathology, or after cardiac arrest, there were too few events (i.e., < 40) to assess any meaningful independent associations.