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The use of Vasoactive-Inotropic Score in Adult Patients with Septic Shock in Intensive Care/Yogun Bakimda Septik Soklu Eriskin Hastalarda Vazoaktif Inotropik Skor Kullanimi.

Introduction

Sepsis is an important cause of mortality and morbidity affecting millions of people around the world every year. According to The Third International Consensus, sepsis is defined as life-threatening organ dysfunction resulting from an irregular response to the host's infection. Septic shock is a condition where vasopressor support is required to maintain a mean arterial pressure of 65 mmHg and above. This condition contains deep circulatory, cellular and metabolic disorders (1). According to the Surviving Sepsis Campaign guideline, when there is hypotension not responding to fluid therapy, various vasopressors and inotropic agents are used, first choice noradrenaline (2). Thus, tissue perfusion is continued and the process of organ dysfunction is prevented (1).

Measuring the amounts of supports used in these patients could help in estimating the outcome. The vasoactive inotropic score (VIS), developed to measure vasopressor support, is mostly used in pediatric patients and cardiac surgery patients (3-6). Also, two studies have used VIS in pediatric sepsis patient groups (7,8). To our best knowledge, there is no present study using VIS in adult septic shock. In our study, we aimed to determine the relationship between VIS which we use to determine the amount of vasopressor and inotropic support and some patient results, especially mortality, in patients with septic shock in our adult intensive care unit (ICU).

Material Method

Consent was obtained from the ethics committee of our hospital (Date: 04.07.2018, number: 2018/269). The data of 18 years old and older patients who were admitted to the Intensive Care Unit of Anesthesiology and Reanimation Department between January 2013 and July 2018 were analyzed retrospectively. Surviving Sepsis Campaign 2012 Guideline and Sepsis-3 Definition were regarded in diagnosis and treatment selection of sepsis and septic shock (1,2). The demographic characteristics of patients diagnosed with sepsis / septic shock, intensive care scores, some laboratory values, sepsis foci, some treatments and intensive care results were recorded. Vasopressor values in the first 48 hours after diagnosis of septic shock were recorded. Only the first septic shock attack was recorded in long-term hospitalized patients. Mean VIS and peak VIS scores were calculated according to these values. The patients were divided into two as survivors and non-survivors, and the relationship between mortality and VIS were examined. Then the data were grouped as mean VIS [greater than or equal to] 10 and peak VIS [greater than or equal to] 10 and statistical analysis was performed.

VIS calculation method

Vasopressor and inotropic support doses were recorded during the first 48 hours after the diagnosis of septic shock in intensive care. The initiation of vasopressor was 0 hours. Then, at 6th, 12th, 24th and 48th hours, doses of vasopressors were recorded. The averages and peak values of the five values recorded during the two-day period were taken. The calculated values for each drug were collected and the total mean VIS and peak VIS values were found. The following formula was used for VIS.

Vasoactive-Inotropic Score = dopamine dose ([micro]g/kg/min) + dobutamine dose ([micro]g/kg/min) + 100 x adrenaline dose ([micro]g/ kg/ min) + 100 x noradrenaline dose ([micro]g/kg/min) + 10 x milrinone dose ([micro]g/kg/min) + 10.000 x vasopressin dose (U/kg/min)

Statistical analysis

Data were statistically analyzed using SPSS Version 22.0 (Statistical Package for the Social Sciences Inc., Chicago, IL, USA). Data were tested for normality with Kolmogorov-Smirnov (with Lilliefors correction) and Shapiro-Wilk tests. Descriptive statistics were performed in all the patient groups; numerical data were expressed as median (quarter intervals) while categorical data were given as percentages. Patients were classified according to mean VIS (VIS<10 or VIS [greater than or equal to] 10), peak VIS (VIS<10 or VIS [greater than or equal to] 10), and ICU outcomes (dead or survive). Patient features were compared using Chi-Square or Fisher's Exact Test for categorical variables and Mann-Whitney U Test for numerical variables. p<0.05 value was accepted as statistically significant. To identify any independent risk factor associated with mortality, among the significant parameters of univariate analysis, the ones which were not associated with each other were entered into the multivariate linear regression analysis. ROC analysis was performed.

Results

General characteristics of patients with sepsis / septic shock

In the study period, 1734 patients were followed in the intensive care unit. The diagnosis of septic shock was 22.6% (392 patients) in these patients. The median ages of the patients were 68 (54.2-79) years, and 239 (61%) were male. Median Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA) values were 24.5 (18-27) and 11 (9-12), respectively. While the duration of ICU stay was 10(4-22) days, the rates of patients with invasive mechanical ventilation, blood and blood products transfusion and acute kidney injury were 96.9% (380 patients), 58.9% (231 patients) and 26.3% (103 patients), respectively. Mortality was 42.1% (165 patients) (Table 1).

Platelet, hemoglobin, white blood cell, procalcitonin and lactate levels were 107 (94-140) (x [10.sup.3]/[micro]L), 9.8(9.1-10.0) (g/dL), 9.5(8.2-13) (x [10.sup.3]/L), 7.9 (4-11.1) (ng/ml) ve 4.2 (2.6-6.0) (mEq/L) respectively. The infection foci of septic shock patients were blood-catheter-borne infection 105(%26.8), urinary system infection 143(%36.5), respiratory system infection 182(%46.4) and soft tissue infection 41(%10.5) (Table 1).

Vasopressor and inotropic drugs used in patients with sepsis / septic shock

Dopamine 188 (47.9%), noradrenaline 365 (93.1%), adrenaline 53 (13.5%) and dobutamine 15 (3.8%) were administered to patients. The mean VIS was 9 (4-15), while the number of mean VIS [greater than or equal to] 10 patients were 192 (49%). Peak VIS values were 11 (5-20) and the number of peak VIS [greater than or equal to] 10 patients were 220 (56.1%) (Table 1).

Patient characteristics according to mortality

The age (74 vs 66 years, p = 0.000), SOFA scores (12 vs 10, p = 0.000) and acute renal failure rates (33.3% vs 21.1%, p = 0.008) were higher in non-survivors. In survivors, the duration of hospitalization were longer (13 vs 8 days, p = 0.000) and the fluid balance were more positive (1600 vs 1100 ml, p = 0.018). Procalcitonin (8.6 vs. 7.7, p = 0.000) and lactate levels (4.6 vs 3.8, p = 0.007) were higher in non-survivors. Survivors had higher rates of urinary tract infection (41% vs 30.3%, p=0.034). The mean VIS score (13 vs 6, p = 0.000), mean VIS [greater than or equal to] 10 (71.5% vs 32.6%, p = 0.000), peak VIS score (16 vs 8, p = 0.000) and peak VIS [greater than or equal to] 10 (73.3% vs 43.6%, p = 0.000) were higher in non-survivors (Table 2).

The data with significant results according to univariate analysis were evaluated with multivariate analysis. The parameters such as age [OR 1.034, 95% CI 1.020-1.049, p=0.000], procalcitonin [OR 1.015, 95% CI 1.003-1.028, p=0.014], lactate [OR 1.161, 95% CI 1.039-1.297, p=0.008], mean VIS [OR 1.123, 95% CI 1.027-1.229, p=0.011], mean VIS [greater than or equal to] 10 [OR 3.455, 95% CI 1.6257.345, p=0.001] and peak VIS score [OR 0.917, 95% CI 0.8510.989, p=0.024] were determined as independent risk factors for mortality (Table 2).

Patient characteristics according to mean VIS [greater than or equal to] 10

Age (71 vs 67 years, p=0.004), SOFA score (12 vs 9, p=0.000), acute renal failure (33.9% vs 19%, p=0.001) and procalcitonin levels (8.6 vs 6.6, p=0.000) were higher in mean VIS [greater than or equal to] 10 patients group, while ICU hospitalization time (8 vs 15.5 days, p=0.000) was shorter (Table 3).

Multivariable logistic regression was performed controlling for patient characteristics. Patients with high mean VIS had significantly greater odds of age [OR 1.018, 95% CI 1.004- 1.033, p=0.014], duration of ICU stay [OR 0.961, 95% CI 0.943-0.979, p=0.000], SOFA score [OR 1.823, 95% CI 1.586-2.094, p=0.000], acute renal failure [OR 2.158, 95% CI 1.183-3.937, p=0.012] and procalcitonin [OR 1.018, 95% CI 1.002-1.033, p=0.023] compared to patients with low mean VIS (Table 3).

Patient characteristics according to peak VIS [greater than or equal to] 10

Age (70 vs 66 years, p=0.014), SOFA score (12 vs 9, p=0.000), acute renal failure (32.3% vs 18.6%, p=0.003) and procalcitonin levels (8.3 vs 6.4, p=0.000) were higher in peak VIS [greater than or equal to] 10 patients group, while ICU hospitalization time (8 vs 16 days, p=0.000) was shorter (Table 4).

Multivariable logistic regression was performed controlling for patient characteristics. Patients with high peak VIS had significantly greater odds of duration of ICU stay [OR 0.958, 95% CI 0.941-0.976, p=0.000], SOFA score [OR 1.785, 95% CI 1.559-2.044, p=0.000] and acute renal failure [OR 2.052, 95% CI 1.112-3.783, p=0.021] compared to patients with low peak VIS (Table 4).

The Correlation Between Mean Cutoff VIS value and Mortality

The cut-off value of mean VIS values according to the receiver operating characteristic (ROC) analysis performed to predict mortality rate was found as 9.75 (Figure 1). The area under the ROC for mean VIS was 0.713 [95% CI 0.662-0.764, p<0.0001], with sensitivity, specificity, and positive and negative predictive values and overall consistency values with 95 % CI of 71.5%, and 66.9 %,61.1%, 76.3% and 68.8%, respectively, at a cutoff [greater than or equal to] 9.75 (Table 5).

Discussion

As far as we know, this is the first study that evaluated VIS in septic shock patients followed in the adult intensive care unit. According to our study, high mean and peak VIS values calculated within the first 48 hours in patients with septic shock may predict the increase in mortality. Mean VIS [greater than or equal to] 10 is an independent risk factor for mortality.

Sepsis, the most common cause of intensive care admission, is also the most common cause of death in the intensive care unit. Despite all advances in treatment, mortality is around 20-30% (9). According to a meta-analysis, mortality rates in ICU in sepsis can reach 40-60% (10). Mortality was 42.1% in our study group. Hypotension occurs in sepsis as a result of venous and arterial vasoplegia, hypovolemia and myocardial depression. In studies, vasopressor agents such as norepinephrine, epinephrine, vasopressin, dopamine, terlipressin, phenylephrine and inotropic agents such as dobutamine, dopexamine, milrinone and levosimendan were used (11). According to the Surviving Sepsis Campaign guideline, norepinephrine is the first choice for vasopressor support when there is no response to fluid therapy in septic shock (1). Norepinephrine reduces mortality. Dopamine with similar effect has undesirable effects such as tachycardia and arrhythmia. Two other drugs, which are often preferred, are epinephrine and vasopressin, reducing the need for norepinephrine. Inotropes may be added to patients with cardiac dysfunction (12). In our study, 93.1% of patients received norepinephrine in the first 48 hours of septic shock. Other drugs have been dopamine, adrenaline and dobutamine.

It is relatively difficult to evaluate the adequacy of fluid therapy in sepsis and septic shock. Conditions such as acute renal failure, heart failure, pulmonary edema and prolonged mechanical ventilation may occur as the amount of fluid support increases. In our study, we found no significant difference in fluid support between the groups. At the same time, there was no difference between steroid support rates in the case of refractory shock. The aim of using vasopressors in septic shock is to maintain tissue perfusion and to prevent the process of organ dysfunction (1). At the same time, we try to save time for eliminating the potential causes (13). Microcirculatory disorders may continue while blood pressure is increased with the use of vasopressors. Besides, vasoconstriction may cause oxygen diffusion disorder at the cellular level (14). In our study, increased lactate levels were independent risk factors for mortality but not with VIS elevation. However, the levels of procalcitonin in our laboratory were independent risk factors for mortality and were also predictive for mean VIS [greater than or equal to] 10.

VIS, which was developed based on the idea that there may be a relationship between the size of these supports given to patients in shock and patient outcomes, has been mostly studied after cardiac surgery and especially in the pediatric patient group. In one study, VIS scores were calculated in infants with cardiopulmonary bypass in congenital heart disease surgery. High maximum VIS values within the first 48 hours postoperatively were associated with poor outcome in terms of cardiac arrest, circulatory support, renal replacement therapy, neurologic injury and death (3). In another study, VIS values calculated in 391 infants who underwent cardiac surgery. The relationship between high VIS values (especially max VIS [greater than or equal to] 20) and poor clinical outcome was found in the first 48 hours in patients who were followed-up in the ICU postoperatively (6).

To our knowledge, only two studies in septic patients and in a group of pediatric patients underwent VIS (7,8). In a study, pediatric sepsis patients (2 months-18 years) in the intensive care unit were evaluated with VIS. VIS values were calculated at the first 6, 12, 24 and 48 hours after diagnosis. The relationship between VIS and ventilator days and ICU hospitalization periods was evaluated as primary and strong correlation was determined between them. In conclusion, it was reported that use of VIS in pediatric sepsis patients might be beneficial (7). In another study, 71 children with fluid refractory septic shock (1 month-16 year of age) evaluated the relationship between VIS and mortality. Mortality was 44% in patients with VIS <20 and 100% in those with VIS [greater than or equal to] 20 (8). A study that reported that only limited data on the use of multiple vasoactive drugs in the ICU revealed that patients who received three or more vasoactive drugs rarely survived (13). In our study, adult septic shock patients were evaluated and both the mean and peak values of VIS were significantly higher in the deceased patient group. Also, mean VIS [greater than or equal to] 10 and peak VIS [greater than or equal to] 10 were associated with mortality, whereas VIS> 10 was an independent risk factor for mortality.

In a study, patients with low cardiac output syndrome (LCOS) at the early postoperative period were examined in pediatric cardiac surgery. Also calculated maximum VIS. LCOS was not associated with duration of mechanical ventilation, ICU stays, hospitalization time and hospital costs. Increased VIS was moderately related to prolonged mechanical ventilation, longer ICU hospitalization and higher total hospital costs, but was not associated with duration of hospitalization (15). In our study, there was no difference between the groups because almost all patients were in mechanical ventilator. However, the duration of ICU hospitalization was significantly lower in patients with higher VIS and also in deceased patients. In a study, the maximum vasoactive-inotropic score (VIS) and inotrope score (IS) were calculated at 24, 48 and 72 hours postoperatively in infants (in 90 days) after cardiovascular surgery. Higher VIS values at 48 hours were strongly associated with increased intubation time and long-term ICU and hospital stay. Both scores were not associated with time to negative fluid balance, peak lactate, and changes in creatinine (4). However, in our study, increased renal insufficiency and increased VIS were statistically associated. Another study examined the relationship between VIS and morbidity and mortality in adult cardiac surgery. The combination of morbidity and mortality were called as 'bad outcome'. A high VIS were associated with a bad outcome. Secondary results were the duration of ICU stay and time to extubation. Patients with high VIS were required longer ICU hospitalization and longer mechanical ventilation. In conclusion, the amount of cardiovascular support at the end of cardiac surgery has been reported to predict morbidity and mortality in adults (16). In our study, there was a significant relationship between advanced age, mean SOFA and mean and peak VIS [greater than or equal to] 10 in both univariate and multivariate analyzes. In another study to determine the relationship between inotropic/vasoactive support and clinical outcomes in children after open heart surgery (208 patients), it was reported that this score could be an excellent tool to measure the severity of the disease, decide on interventions, and provide parental counselling in pediatric cardiac surgery ICUs (17).

In a study, adolescents with congenital heart disease (10-18 years) were examined with VIS postoperatively. Maximum VIS values at 24 and 48 hours were significantly associated with increased hospitalization and prolonged weaning periods. According to cutoff> 4.75, the area under the ROC for the max VIS was 0.76, while the sensitivity, specificity, positive predictive value and negative predictive value were 67%, 74%, 36% and 91%, respectively. It has been proposed that this simple score can be used as a prognostic indicator (18). In our previous study in which the relationship between VIS score and mortality in patients with severe head trauma followed in adult intensive care unit was 72.7%, 74.1%, 68.1% and 78.2% for the cutoff value of mean VIS [greater than or equal to] 7.5, respectively (19). In this study, according to the ROC analysis, the cut-off value of VIS 9.75 was taken, and the AUC value was 0.713 when the mortality was estimated. Sensitivity-specificity positive predictive value and negative predictive value were 71.5%, 66.9%, 61.1% and 76.3%, respectively.

Limitations

Our study has some limitations. First, our study was performed in a single-center and single intensive care unit and the data were retrospective. Second, our sepsis patients were heterogeneous and were followed up and treated by different clinicians during the long study period. Thirdly, clinical findings, central venous pressure and passive leg raising have been used to assess fluid status. Very few patients had bedside echocardiography and PICCO. Fourthly, the dose increase of vasopressor drugs was made according to the clinician's decision, accompanied by local protocols for ICU. We also did not have any protocol with maximum drug doses. Finally, there was no vasopressin in our hospital and therefore it was not used for VIS calculation.

Conclusion

We believe that vasoactive-inotropic score which is easy to calculate, does not require any laboratory examination, may be useful in predicting outcome in adult septic shock patients followed in the intensive care unit.

https://doi.org/10.33381/dcbybd.2019.2057

Ethics Committee Approval: Ethics committee approval was received for this study from the ethics committee of Selcuk University Faculty of Medicine (Approval Date: 04.07.2018 / No: 2018/269).

Peer-review: Externally peer-reviewed.

Conflict of Interest: Authors have no conflicts of interest to declare.

Financial Disclosure: The authors declared that this study has received no financial support.

Etik Komite Onayi: Bu calisma icin etik kurul onayi Selcuk Universitesi Tip Fakultesi etik kurulundan alinmistir (Onay Tarihi: 10.10.2018 / Oturum No: 04.07.2018/ No: 2018/269).

Hakem Degerlendirmesi: Dis bagimsiz.

Cikar Catismasi: Yazarlar cikar catismasi bildirmemislerdir.

Finansal Destek: Yazarlar bu calisma icin finansal destek almadiklarini beyan etmislerdir.

References

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(2.) Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012. Crit Care Med. 2013 Feb; 41(2): 580-637. [CrossRef]

(3.) Gaies MG, Gurney JG, Yen AH, et al. Vasoactive-Inotropic Score as a predictor of morbidity and mortality in infants after cardiopulmonary bypass. Pediatr Crit Care Med 2010; 11: 234-238. [CrossRef]

(4.) Davidson J, Tong S, Hancock H, et al. Prospective validation of the Vasoactive-Inotropic Score and correlation to short-term outcomes in neonates and infants after cardiothoracic surgery. Intensive Care Med 2012; 38: 1184-1190. [CrossRef]

(5.) Butts RJ, Scheurer MA, Atz AM, et al. Comparison of maximum Vasoactive Inotropic Score and low cardiac output syndrome as markers of early postoperative outcomes after neonatal cardiac surgery. Pediatr Cardiol 2012; 33: 633-638. [CrossRef]

(6.) Gaies MG, Jeffries HE, Niebler RA, Pasquali SK, Donohue JE, Yu S, Gall C, Rice TB, Thiagarajan RR. Vasoactive-inotropic score is associated with outcome after infant cardiac surgery: An analysis from the pediatric cardiac critical care consortium and virtual PICU system registries. Pediatr Crit Care Med 2014; 15(6): 529-37. [CrossRef]

(7.) McIntosh AM, Tong S, Deakyne SJ, Davidson JA, Scott HF. Validation of the vasoactive-inotropic score in pediatric sepsis. Pediatr Crit Care Med 2017; 18(8): 750-757. [CrossRef]

(8.) Haque A, Siddiqui NR, Munir O, Saleem S, Mian A. Association between vasoactive-inotropic score and mortality in pediatric septic shock. Indian Pediatr 2015; 52(4): 311-313. [CrossRef]

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(10.) Avni T, Lador A, Lev S, Leibovic L, Paul M, Grossman A. Vasopressors for the Treatment of Septic Shock: Systematic Review and Meta-Analysis. PLoS One. 2015 Aug 3;10(8):e0129305. [CrossRef]

(11.) Gelinas JP, Russell JA. Vasopressors During Sepsis: Selection and Targets. Clin Chest Med 2016; 37:251-62. [CrossRef]

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(13.) Prys-Picard CO, Shah SK, Williams BD, Cardenas V, Sharma G. Outcomes of patients on multiple vasoactive drugs for shock. Journal of Intensive Care Medicine 2012; 28(4): 237-240. [CrossRef]

(14.) Stratton L, Berlin DA, Arbo JE. Vasopressors and Inotropes in Sepsis. Emerg Med Clin N Am 2017; 35: 75-91. [CrossRef]

(15.) Butts RJ, Scheurer MA, Atz AM, et al. Comparison of maximum Vasoactive Inotropic Score and low cardiac output syndrome as markers of early postoperative outcomes after neonatal cardiac surgery. Pediatr Cardiol 2012; 33: 633-638. [CrossRef]

(16.) Yamazaki Y, Oba K, Matsui Y, Morimoto Y. Vasoactive-inotropic score as a predictor of morbidity and mortality in adults after cardiac surgery with cardiopulmonary bypass. Journal of Anesthesia 2018; 32: 167-173. [CrossRef]

(17.) Kumar M, Sharma R, Sethi SK, Bazaz S, Sharma P, Bhan A, Kher V. Vasoactive Inotrope Score as a tool for clinical care in children post cardiac surgery. Indian Journal of Critical Care Medicine 2014; 18(10): 653-658. [CrossRef]

(18.) Garcia RU, Walters III HL, Delius RE, Aggarwal S. Vasoactive inotropic score (VIS) as biomarker of short-term outcomes in adolescents after cardiothoracic surgery. Pediatr Cardiol 2016; 37: 271-277. [CrossRef]

(19.) Kara I, Sargin M, Bayraktar YS, Sahinoglu M, Ildarov G, Duman I, Celik JB, Karabagli H. The Relationship Between Vasoactive-Inotropic Score and Mortality in Adult Patients with Traumatic Brain Injury. [CrossRef]

Iskender KARA [1] [ID], Mehmet SARGIN [2] [ID], Yesim Serife BAYRAKTAR [1] [ID], Hatice EYIOL [2] [ID], Ipek DUMAN [3] [ID], Jale Bengi CELIK [1] [ID]

[1] Selcuk University, Faculty of Medicine, Anesthesiology and Reanimation, Critical Care Medicine, Konya, Turkiye

[2] Selcuk University, Faculty of Medicine, Anesthesiology and Reanimation, Konya, Turkiye

[3] Necmettin Erbakan University, Meram Faculty of Medicine, Department of Medical Pharmacology, Konya, Turkiye

Corresponding Author / Sorumlu Yazar: Iskender Kara

E mail: driskenderkara@gmail.com

Received/Gelis: 15.03.2019

Accepted/Kabul: 25.03.2019

Available online/ Cevrimici yayin: 28.03.2019

Caption: Figure 1. Receiver operating characteristic (ROC) curve for mean Vasoactive-inotropic score
Table 1. General characteristics of patients with sepsis/septic shock

Characteristics

Age (years)                                 68(54.2-79)
Gender (male)                                239(61%)
ICU admission time (days)                    10(4-22)
SOFA score                                   11(9-12)
APACHE II score                             24.5(18-27)
Mechanical ventilation                      380(96.9%)
Acute renal failure                         103(26.3%)
Blood products transfusion                  231(58.9%)
Steroid support                              91(23.2%)
Fluid balance (ml)                        1600(700-2150)
Outcome (Exitus)                            165(42.1%)
Laboratory
Platelets (x[10.sup.3] /pL)                 107(94-140)
Hemoglobin (g/dL)                          9.8(9.1-10.0)
White blood cell (x[10.sup.3] /L)           9.5(8.2-13)
Procalcitonin (ng/ml)                       7.9(4-11.1)
Lactate (mEq/L)                            4.2(2.6-6.0)
Anatomic localizations of
infectious foci
Blood-catheter borne infection              105(26.8%)
Urinary system infection                    143(36.5%)
Respiratory system infection                182(46.4%)
Soft tissue infection                        41(10.5%)
Supportive Therapies and Vasoactive
Inotropic Score
Mean dopamine (188 patients)                 5(2.5-8)
Mean noradrenaline (365 patients)             7(4-10)
Mean adrenaline (53 patients)                5(3.5-7)
Mean dobutamine (15 patients)                 5(4-10)
Mean Vasoactive Inotropic                     9(4-15)
Score ([micro]g/kg/min)
Mean Vasoactive Inotropic Score              192(49%)
[greater than or equal to] 10
Peak dopamine ([micro]g/kg/min)               7(5-10)
Peak noradrenaline ([micro]g/kg/min)          8(5-12)
Peak adrenaline ([micro]g/kg/min)             6(5-7)
Peak dobutamine ([micro]g/kg/min)             7(4-10)
Peak Vasoactive Inotropic Score              11(5-20)
([micro]g/kg/min)
Peak Vasoactive Inotropic Score             220(56.1%)
[greater than or equal to] 10

Data are presented as median (IQR) or n (%). ICU: Intensive Care Unit,
SOFA: Sequential Organ Failure Assessment, APACHE II: Acute
Physiology and Chronic Health Evaluation 2

Table 2. Patient characteristics according to mortality

                                     Univariate Analysis

                             Survivors       Non-survivors
Variables                     (n=227)           (n=227)       p value

Age (years)                  66(49-75)         74(63-83)       0.000
Gender (male)               135(59.5%)         104(63%)        0.529
ICU admission                13(5-26)           8(2-17)        0.000
time (days)
SOFA score                   10(8-12)          12(10-13)       0.000
APACHE II score              24(16-27)        25(20-26.5)      0.147
Mechanical                  222(97.8%)        158(95.8%)       0.374
ventilation
Acute renal failure          48(21.1%)         55(33.3%)       0.008
Blood products              130(57.3%)        101(61.2%)       0.467
transfusion
Steroid support              50(22.0%)         41(24.8%)       0.340
Fluid balance (ml)        1600(800-2400)    1100(700-2125)     0.018
Laboratory
Platelets                   106(94-138)       108(92-143)      0.416
(x 103 /[micro]L)
Hemoglobin (g/dL)          9.8(9.1-10.1)      9.7(8.9-10)      0.151
White blood cell             9.5(8-12)        10(8.5-14)       0.219
(x 103 /L)
Procalcitonin (ng/ml)       7,7(3,2-10)      8.6(5.2-14.3)     0.000
Lactate (mEq/L)            3.8(2.4-5.4)      4.6(2.6-6.5)      0.007
Anatomic
localizations of
infectious foci
Blood-catheter               64(28.2%)         41(24.8%)       0.490
borne infection
Urinary system                93(41%)          50(30.3%)       0.034
infection
Respiratory                 110(48.5%)         72(43.6%)       0.358
system infection
Soft tissue                   25(11%)          16(9.7%)        0.740
infection
Vasoactive
Inotropic Score
Mean VIS                      6(3-12)         13(6-19.5)       0.000
([micro]g/kg/min)
Mean VIS [greater            74(32.6%)        118(71.5%)       0.000
than or equal to] 10
Peak VIS                      8(4-15)         16(8.5-22)       0.000
([micro]g/kg/min)
Peak VIS [greater            99(43.6%)        121(73.3%)       0.000
than or equal to] 10

                              Multivariate analysis

                                    OR
Variables                   (CI 95% low-upper)         p

Age (years)                 1.034(1.020-1.049)       0.000
Gender (male)
ICU admission                                          NS
time (days)
SOFA score                                             NS
APACHE II score
Mechanical
ventilation
Acute renal failure                                    NS
Blood products
transfusion
Steroid support
Fluid balance (ml)                                     NS
Laboratory
Platelets
(x 103 /[micro]L)
Hemoglobin (g/dL)
White blood cell
(x 103 /L)
Procalcitonin (ng/ml)       1.015(1.003-1.028)       0.014
Lactate (mEq/L)             1.161(1.039-1.297)       0.008
Anatomic
localizations of
infectious foci
Blood-catheter
borne infection
Urinary system              0.521(0.318-0.852)       0.009
infection
Respiratory
system infection
Soft tissue
infection
Vasoactive
Inotropic Score
Mean VIS                    1.123(1.027-1.229)       0.011
([micro]g/kg/min)
Mean VIS [greater           3.455(1.625-7.345)       0.001
than or equal to] 10
Peak VIS                    0.917(0.851-0.989)       0.024
([micro]g/kg/min)
Peak VIS [greater                                      NS
than or equal to] 10

Data are presented as median (IQR) or n (%). ICU: Intensive Care
Unit, SOFA: Sequential Organ Failure Assessment, APACHE II: Acute
Physiology and Chronic Health Evaluation 2, VIS: Vasoactive
Inotropic Score

Table 3. Patient characteristics according to mean VIS
[greater than or equal to] 10

                                  Univariate Analysis

                                               Mean VIS
                                            [greater than
                           Mean VIS <10     or equal to] 10
Variables                     n = 200            n=192          p

Age (years)                 67(49-77.5)        71(59-80)      0.004
Gender (male)               115(57.5%)        124(64.6%)      0.178
ICU admission              15.5(6-28.7)         8(2-15)       0.000
time (days)
SOFA score                    9(8-11)          12(12-13)      0.000
APACHE II score             24.5(16-27)       24.5(20-26)     0.636
Mechanical                   196(98%)         184(95.8%)      0.251
ventilation
Acute renal                   38(19%)          65(33.9%)      0.001
failure
Blood products               120(60%)         111(57.8%)      0.682
transfusion
Steroid support               46(23%)          45(23.4%)      0.830
Fluid balance (ml)        700(1600-2400)    1600(700-2150)    0.147
Laboratory
Platelets                   104(95-138)       110(90-141)     0.626
(x 103 /[micro]L)
Hemoglobin (g/dL)          9.8(9.1-10.1)      9.7(9.1-10)     0.235
White blood cell            9.5(8-12.2)       10(8.5-14)      0.199
(x 103 /L)
Procalcitonin              6.6(3.2-9.3)      8.6(6.1-17.5)    0.000
(ng/ml)
Lactate (mEq/L)            4.1(2.4-5.4)       4.3(2.6-6)      0.220
Anatomic localizations
of infectious foci
Blood-catheter               55(27.5%)          50(26%)       0.820
borne infection
Urinary system                76(38%)          67(34.9%)      0.531
infection
Respiratory                  110(55%)          72(37.5%)      0.001
system infection
Soft tissue                   28(14%)          13(6.8%)       0.021
infection

                             Multivariate analysis

Variables                       OR(CI%95)           p

Age (years)                1.018(1.004-1.033)     0.014
Gender (male)
ICU admission              0.961(0.943-0.979)     0.000
time (days)
SOFA score                 1.823(1.586-2.094)     0.000
APACHE II score
Mechanical
ventilation
Acute renal                2.158(1.183-3.937)     0.012
failure
Blood products
transfusion
Steroid support
Fluid balance (ml)
Laboratory
Platelets
(x 103 /[micro]L)
Hemoglobin (g/dL)
White blood cell
(x 103 /L)
Procalcitonin              1.018(1.002-1.033)     0.023
(ng/ml)
Lactate (mEq/L)
Anatomic localizations
of infectious foci
Blood-catheter
borne infection
Urinary system
infection
Respiratory                                         NS
system infection
Soft tissue                                         NS
infection

Data are presented as median (IQR) or n (%). ICU: Intensive Care
Unit, SOFA: Sequential Organ Failure Assessment, APACHE II: Acute
Physiology and Chronic Health Evaluation 2, VIS: Vasoactive
Inotropic Score

Table 4. Patient characteristics according to peak VIS
[greater than or equal to] 10

                                    Univariate Analysis

                                               Peak VIS
                                             [greater than
                           Peak VIS <10     or equal to] 10
Variables                     n= 172             n=220       p

Age (years)                 66(48.2-78)        70(58-79)     0.014
Gender (male)               104(60.5%)        135(61.4%)     0.917
ICU admission                16(7-30)           8(2-16)      0.000
time (days)
SOFA score                    9(8-10)          12(11-13)     0.000
APACHE II score             24.5(16-27)       24.5(20-27)    0.550
Mechanical                  170(98.8%)        210(95.5%)     0.075
ventilation
Acute renal failure          32(18.6%)         71(32.3%)     0.003
Blood products               105(61%)         126(57.3%)     0.470
transfusion
Steroid support              40(23.2%)         51(23.1%)     1.000
Fluid balance (ml)        1600(700-2400)    1600(700-2150)   0.388
Laboratory
Platelets                   103(95-139)       109(90-140)    0.776
(x103 /[micro]L)
Hemoglobin (g/dL)          9.8(9.1-10.1)      9.7(9.1-10)    0.218
White blood cell           9.5(8.5-12.8)      9.5(8-13.3)    0.774
(x103 /L)
Procalcitonin             6.45(3.2-9.17)     8.3(5.5-14.3)   0.000
(ng/ml)
Lactate (mEq/L)            4.1(2.6-5.4)       4.3(2.6-6)     0.216
Anatomic localizations
of infectious foci
Blood-catheter               47(27.3%)         58(26.4%)     0.909
borne infection
Urinary system               63(36.6%)         80(36.4%)     1.000
infection
Respiratory                   98(57%)          84(38.2%)     0.000
system infection
Soft tissue                  25(14.5%)         16(7.3%)      0.030
infection

Variables                   Multivariate analysis

Age (years)                                         NS
Gender (male)
ICU admission              0.958(0.941-0.976)     0.000
time (days)
SOFA score                 1.785(1.559-2.044)     0.000
APACHE II score
Mechanical
ventilation
Acute renal failure        2.052(1.112-3.783)     0.021
Blood products
transfusion
Steroid support
Fluid balance (ml)
Laboratory
Platelets
(x103 /[micro]L)
Hemoglobin (g/dL)
White blood cell
(x103 /L)
Procalcitonin                                       NS
(ng/ml)
Lactate (mEq/L)
Anatomic localizations
of infectious foci
Blood-catheter
borne infection
Urinary system
infection
Respiratory                                         NS
system infection
Soft tissue                                         NS
infection

Data are presented as median (IQR) or n (%). ICU: Intensive Care
Unit, SOFA: Sequential Organ Failure Assessment, APACHE II: Acute
Physiology and Chronic Health Evaluation 2, VIS: Vasoactive
Inotropic Score

Table 5. ROC analysis for the prediction of mortality. Cut-off
mean VIS value for survivors versus non-survivors based on ROC
analysis

                              AUC             p value

Mean VIS                     0.713             0.000

                             Exitus

                      Yes     No     Total
Mean          Yes     118     75      193

VIS=9,75      No      47      152     199

             Total    165     227

                     Asymptotic 95 %
                   confidence intervals         Cut-off
                 lower bound-upper bound         value

Mean VIS               0.662-0.764               [greater than or
                                                    equal to] 9.75

Exitus        Sensitivity = 118/165 = 71.5%
              Specificity = 152/227 = 66.9%
Mean               Positive predictive
                 value = 118/193 = 61.1%
VIS=9,75           Negative predictive
                 value = 152/199 = 76.3%
                   Total consistency =
                   118+152/392 = 68.8%

ROC: Receiver operating characteristic, AUC: Area
under the curve, VIS: Vasoactive-inotropic score.
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Title Annotation:ORIGINAL INVESTIGATION/OZGUN ARASTIRMA
Author:Kara, Iskender; Sargin, Mehmet; Bayraktar, Yesim Serife; Eyiol, Hatice; Duman, Ipek; Celik, Jale Ben
Publication:Dahili ve Cerrahi Bilimler Yogun Bakim Dergisi (Journal of Medical and Surgical Intensive Care Medic
Date:Apr 1, 2019
Words:5580
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