Performance Differences Among Variations Of Systolic, Diastolic, And Mean Arterial Pressures In Prognosticating Mortality In Critically Ill Patients Who Are Taking Norepineprine

Admitted patients and may be used to predict the prognosis of patients with septic shock. Sepsis is a complex syndrome caused by the body’s systemic response to an infection with a major cause of high treatment cost, single or multiple organ dysfunctions.^[1-4] C-reactive protein (CRP) is also a useful positive acute-phase reactant marker that can predict morbidity and mortality among critically ill patients. ^[5,6]  However, the results of CRP and other severity indices of sepsis may not be immediately available upon request, potentially delaying effective dynamic risk stratification and goal directed management in these unstable studied cohort. MAP which defined as 1/3 SBP + 2/3 DBP is a readily and affordable attained comprehensive parameter that combines two physiological pressure parameters (SBP and DBP) into a single parameter and previously has been shown to stratify and served as an early warning prognosticator of high risk septic patients from various aetiologies when compared to SBP and DBP.^[7-10] Having reliable indicators and markers that would help prognosticate the survival of these patients is invaluable and would subsequently assist in the course of effective treatment.^[11,12] Our objective was to compare the ability of %DBP, %SBP, and %MAP variations to predict the primary outcome of overall 28-day ICU mortality, and the secondary outcomes of early mortality (≤14 days), late mortality (>14 days), and ICU length of stay (LOS). Also, our objective was to determine the optimal cut-off point, sensitivity (TPR), specificity (TNR), Youden’s index (YI), positive and nega­tive predictive values (PPV and NPV), and accuracy index (AI), of the three tested prognosticators.

Methods

This was a single-centre observational retrospective study conducted in the department of adult ICU of King Hussein Medical Hospital (KHMH) at Royal Medical Services (RMS) in Jordan. This study was approved by our Institutional Review Board (IRB), and a requirement for consent was waived owing to its retrospective design. This study included a cohort of 913 critically ill patients admitted to our adult ICU via the emergency department (ED) or via other hospital wards with any medical or surgical problems. After excluded all patients who were died or discharged before completed at least 1 week after admission and included all critically ill patients who their anthropometrics, diagnostics, demographics, hemodynamics, nutritional indices, and all required laboratory data were known, 163 critically ill patients were finally included in our study. Flow chart of critically ill patient’s selection and data collection process is fully illustrated in Figure 1.

All patient continuous variables were expressed as mean± standard deviation by using the independent samples T-test while categorical and ordinal variables were expressed as numbers with percentages by using the chi square test or as median (interquartile range) by using the Mann-Whitney U test, respectively. Analysis values were compared for the two tested groups (survivors vs. non-survivors) and the non-survival group was further analysed after being divided into 2 subgroups, early (≤14 days) and late (>14 days) mortality. A receiver operating char­acteristic (ROC) curve followed by sensitivity analysis was used to determine the area under the ROC curves (AUROCs), predictive performances, and the optimal cut-off values for %SBP_var, %MAP_var, and %DBP_var, YI, TPR, TNR, PPV, NPV, and AI were also calculated.  Statistical analyses were performed using IBM SPSS ver. 25 (IBM Corp., Armonk, NY, USA) and P-values ≤0.05 were considered sta­tistically significant.

 

Result

The mean overall age was 58.37±9.96 years. 112 subjects (68.71%) were male and 51 subjects (31.29%) were female. The overall 28-day, early, and late ICU mortality rate were 39.26% (64 patients), 9.82% (16 patients), and 29.45% (48 patients), respectively. 28-day ICU mortality was significantly higher in medically than surgically admitted patients (85.94% (55 medically patients) versus 14.06% (9 surgically patients), respectively). Baseline pre-ICU admission days and number of co-morbidities >1 were also significantly higher in non-survivors than survivors (7.42±4.57 days versus 2.23±1.06 days and 65.63% (42 subjects) versus 47.47% (47 subjects), respectively). Despite baseline albumin level (ALB₁) was significantly higher in non-survivors (2.94±0.39 g/dl) than survivors (2.63±0.20 g/dl), survivors had significantly higher average administered human albumin (H.ALB) doses and nutritional protein density (PD) inputs and significantly lower CRP (18.89±3.16 g/day and 3.72±0.74 g/100 Cal and 28.38±14.38 mg/dl, respectively) than non-survivors (14.06±6.09 g/day and 3.50±0.36 g/100 Cal and 43.09±19.28 mg/dl, respectively) which ultimately resulted in significantly higher average ALB during ICU admission in survivors (2.87±0.12 g/dl) than in non survivors (2.57±0.13 g/dl). The ICU and overall hospital LOS were also significantly lower in survivors non survivors (9.23±1.06 days and 11.46±2.12 days versus 17.30±4.14 days and 24.72±1.98 days, respectively).

All haemodynamic parameters of SBP_max, SBP_min, and SBP_avg versus MAP_max, MAP_min, and MAP_avg versus DBP_max, DBP_min, and DBP_avg versus were significantly higher values in survivors (113.77±3.15 mmHg, 103.77±3.15 mmHg, and 111.77±3.15 mmHg versus 87.04±3.16 mmHg, 73.77±3.15 mmHg, and 81.77±3.15 mmHg versus 73.44±3.30 mmHg, 58.64±3.23 mmHg, and  66.65±3.20 mmHg, respectively) than in non-survivors (98.41±16.13 mmHg, 88.41±16.13 mmHg, and 96.41±16.13 mmHg versus 72.14±14.81 mmHg, 58.99±13.98 mmHg, and 66.76±14.70 mmHg versus  57.26±17.02 mmHg, 42.99±16.46 mmHg, and 51.03±16.47 mmHg, respectively).

Our studied three prognosticators of %SBP_var, %MAP_var, and %DBP_var were significantly lower in survivors in compared with non survivors (8.96%±0.26%, 16.34%±0.65%, and 22.52%±1.10% versus 11.04%±4.61%, 21.17%±7.54%, and 35.18%±29.37%, respectively). There were insignificant differences between the two tested groups regarding average child-Pugh score, average Glasgow coma scale (GSC), average NE infusion rate, and total calories (TC) inputs. Demographics, admission co-morbidities and class, anthropometrics, and follow-up comparison data of the study’s critically ill patients are fully summarised in Table 1 and Table 2, respectively. Table 3 shows the optimal cut-off point, TPR, TNR, YI, PPV, NPV, and AI of the tested prognostic indicators. The best cut-off values for %SBP_var, %MAP_var, and %DBP_var in our study were 12.26%, 18.49%, and 105.11% for overall 28-day ICU mortality. The area under curve of (ROC) AUROC of %MAP_var (0.818; 95% CI, 0.738-0.897) was significantly greater than those of %SBP_var (0.769; 95% CI, 0.678-0.859) and %DBP_var (0.265; 95%, 0.179-0.350). Fig 1 illustrates the ROC curve analysis for the three tested prognosticators of the overall 28-day ICU mortality.

Discussion

The present study included septic mechanically ventilated critically ill patients who were taking norepinephrine as a vasopressor at an overall average rate of 9.53±1.79 mcg/min. To the best of our knowledge, this is the first study that compare the prognosticating performance of three pressure parameters of SBP, MAP, and DBP using there’s percentage variations based on the concept of dynamic changes, instabilities, and high acuities of septic critically ill patients.^[13-16] Vital sign dependent on blood pressure (BP) emphasises current physiologic no-cost bedside triage dynamic rather than static tools that can be used at any time for triage decisions and appropriately assigning a higher priority to sicker septic patients in the context of ever-shrinking resources, early stratification with fast, affordable, valid, reliable, and discriminative predictive tools while waiting for the results of other diagnostics_.^[17-20] After careful analysis of the data, %MAP_var demonstrated significantly higher sensitivity, performance, negative predictive value, and accuracy than %SBP_var followed by %DBP_var (87.10%, 58.90%, 89.59%, and 77.81% versus 83.90%, 45.00%, 85.44%, and 70.05% versus 15.60%, 15.60%, 64.70%, and 66.86%, respectively). This study demonstrates a vast difference in predictive values of BP percentage variations, possibly due to the fact that fluid resuscitation and norepinephrine, which were primarily used in these septic mechanically ventilated critically ill studied patients, gives rise to alterations of physiological parameters of heart rate (HR), stroke volume (SV), cardiac output (CO), and systemic vascular resistance (SVR), making the BP percentage variations especially %MAP_var indicator a realistic reflection of the septic patients and a more reliable predictive prognosticator compared to with other non-dynamic indicators such as CRP and pro-calcitonin, lactate, and white blood cells (WBCs).^[21-24]

In summary, %MAP_var prognosticator and %SBP_var were an effective, no-cost bedside modalities, and discriminative prognosticators with realistic, reliable, and readily available red flag bedside assessment tools which had high sensitivity, performance, and accuracy to predict early, late, and overall 28-day ICU mortality in septic mechanically ventilated critically ill patients who are taking norepinephrine as a vasopressor.^[25-27] This study is limited by its retrospective design, using single-centre data, including only septic mechanically ventilated ICU patients. Nonetheless, our centre is an experienced and high-volume unit, so our data may be useful in other centres. A larger, multisite, and prospective study is needed to control for multiple confounders.

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