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In the era of quality-based medicine, high-risk neurosurgical patients represent a considerable proportion of intensive care unit (ICU) admissions aiming to fulfill the gap of treatment standard and expecting the best clinical outcome. However, some recent studies showed the mortality in neurosurgical ICU to be three times higher than in general ICU, accounting for 22.5%-24.8% of the in-hospital mortality and 39.8% of the mortality after 1 year (1-3). Information derivable from effective mortality predicting tools may facilitate the appropriate administrative management rationale among the scarcity of healthcare resources and help guiding physician for proper evidence-based decision-making.

A widely used ICU prognostic scoring model, the Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring system has been recognized. It has shown to be an accurate measurement of patient severity and correlates strongly with outcome in critical patients (4,5). The highly differentiated affinity among critically ill patients was shown by the AUC of 0.806-0.892 (6-9). The familiarity is achieved because of its less variables and no calculation converted for any sea levels affected (4,10). The APACHE II score can compare and benchmark for the effectiveness, efficacy and quality matter of each unit individually (11,12). Nonetheless, the qualified systematic database indicating APACHE II score, i.e. patient diagnosis, clinical condition, scientific parameters and laboratory values could hardly be established in routine (13,14). Particularly in fragile neurosurgical patients, the clinical condition may alter and need specific treatment immediately.

The length of stay is one of the most concerned issues not only for the healthcare personnel but also the patients, relatives and health insurance providers (15). Some literature data indicate that the mean length of ICU stay is 4.5-6.0 days for the patient undergoing craniotomy with blood clot removal, 1.8-2.9 days for the patient undergoing craniotomy without blood clot removal, and 11.2[+ or -]15.4 days for stroke patients (16). However, there is still no strong evidence supporting the validity of the length of hospital stay estimators in these groups of patients.

From the critical appraisal process, few articles reviewed the value of APACHE II score and performance of mortality prediction in subspecialty ICUs that have different case-mix and different providermix such as neurosurgical ICU (3). The discordance between the predictive implications, particularly on some specific neurosurgical disease conditions that were not generalized to the others, was mentioned (17). Therefore, this retrospective study was performed to present the severity of illness by acknowledging the APACHE II score among neurosurgical ICU patients, to predict mortality reffecting APACHE II performance, and to evaluate the relationship of APACHE II score parameters as if they could estimate the length of hospital stay.

Patients and Methods

This study had been registered at the Tai Clinical Trials Registry with the identification number of TCTR 20150925001. Approval for the study (No. 10/2555) was received from the Prasat Neurological Institutional Ethics Committee (Chairman: Suchart Hanchaipiboonkul) on February 8, 2012, and written informed consent was obtained from all patients or legal relatives in case of unconsciousness. All patients admitted to neurosurgical ICU at Prasat Neurological Institute, Bangkok, between February 1 and July 31, 2011 were recruited. Demographics and the parameters indicating APACHE II score were collected within 30 minutes after admission by certified neurosurgical registrar nurses. The score calculation software was developed based on Microsoft Excel 2007 software (Seattle, WA, 2007) to convert those parameters, i.e. body temperature, mean arterial pressure, heart rate, respiratory rate, alveolar-arterial oxygen (A-a) gradient; if fractional inspired oxygen concentration is [greater than or equal to]0.5, arterial oxygen tension (Pa[O.sub.2]); if fractional inspired oxygen concentration is <0.5, serum bicarbonate (HC[O.sub.3]); if there is no arterial blood gas analysis, arterial pH, serum sodium, serum potassium, creatinine, hematocrit, white blood cell count, Glasgow Coma Scale score, age and medical condition were entered into the APACHE II score, as shown in Figure 1 (4). The adjusted predicted risk of death (R) for each patient was calculated based on the patient's APACHE diagnosis, APACHE II score, and surgical status by using the APACHE II risk of death equation [ln (R/1-R)= -3.517 + (APACHE II score x 0.146) + (0.603, only if postoperative emergency surgery) + (diagnostic category weight, as indicated in listing of diagnostic categories leading to ICU admission)] (4). The length of stay and Glasgow Outcome Scale score were also recorded at unit discharge and hospital discharge. The observed death rate was compared with the risk-adjusted death prediction for the study population.

This retrospective study was performed within a 6-month period, expected to recruit 250 patients at least. The NQuery Advisor software version 6.0 (Boston, MA, 2005) was calculated to reassure the power of this study according to Park et al. (3), which showed the adjusted predicted mortality rate in neurosurgical ICU. Finally, it was found that the power would increase to 99% if capable to detect the difference between the null hypothesis proportion of 0.38 and the alternative proportion of 0.25, with the sample size of 228, a single group t-test with a 0.05 two-sided significance level.

For demographic data, descriptive statistics was used and reported as mean, standard deviation (SD), 95% confidence interval (95% CI), number and percent. The area under the receiver operating characteristic curve (AUC) was analyzed, as well as the optimal cut point to demonstrate the capability of APACHE II score to predict death rate. Pearson's correlation was conducted using the SPSS software version 16 (Markham, Ontario, Canada, 2007) to determine the correlation of APACHE II score and the length of stay. If the correlation is over 0.8 at p-value <0.05, the predictive property of APACHE II parameters and the length of stay are further analyzed with the general linear model. The values were expressed as mean difference and 95% CI.
Fig. 1. Summary variables and calculation methods for Acute Physiology
and Chronic Health Evaluation (APACHE) II score.

Physiologic Variable                              +4

 1. Temperature ([degrees]C)           [greater than or equal to]41
 2. Mean arterial pressure (mmHg)     [greater than or equal to]160
 3. Heart rate (/min)                 [greater than or equal to]180
 4. Respiratory rate (/min)            [greater than or equal to]50
 5. Oxygenation (mmHg)
    a. A-aD[O.sub.2] if Fi[O.sub.2]
       [greater than or equal to]0.5                            500
    b. Pa [O.sub.2] if Fi[O.sub.2]
 6. Acid-base balance
    a. Arterial pH                      [greater than or equal to]7.7
    b. Serum HC[O.sub.3] (mEq/l)       [greater than or equal to]52
       if no arterial blood gas
 7. Sodium (mEq/l)                    [greater than or equal to]180
 8. Potassium (mEq/l)                   [greater than or equal to]7
 9. Creatinine (mg/dl)                  [greater than or equal to]3.5
10. Hematocirt (%)                     [greater than or equal to]60
11. White blood count
    (x1000/[mm.sup.3])                 [greater than or equal to]40
12. Glasgow Coma Score (GCS)           Score = 15 minus actual GCS

Physiologic Variable                    +3          +2          +1

 1. Temperature ([degrees]C)           39-40.9                38.5-38.9
 2. Mean arterial pressure (mmHg)     130-159     110-129
 3. Heart rate (/min)                 140-179     110-139
 4. Respiratory rate (/min)            35-49                  25-34
 5. Oxygenation (mmHg)                            200-349
    a. A-aD[O.sub.2] if Fi[O.sub.2]
       [greater than or equal to]0.5  350-499
    b. Pa [O.sub.2] if Fi[O.sub.2]
 6. Acid-base balance
    a. Arterial pH                      7.6-7.69               7.5-7.59
    b. Serum HC[O.sub.3] (mEq/l)       41-51.9                32-40.9
       if no arterial blood gas
 7. Sodium (mEq/l)                    160-179     155-159    150-154
 8. Potassium (mEq/l)                   6-6.9                  5.5-5.9
 9. Creatinine (mg/dl)                  2-3.4       1.5-1.9
10. Hematocirt (%)                                 50-59.9    46-49.9
11. White blood count                              20-39.9    15.19.9
12. Glasgow Coma Score (GCS)

Physiologic Variable                      0          +1         +2

 1. Temperature ([degrees]C)            36-38.4     34-35.9   32-33.9
 2. Mean arterial pressure (mmHg)       70-109                50-69
 3. Heart rate (/min)                   70-109                55-69
 4. Respiratory rate (/min)             12-24       10-11      6-9
 5. Oxygenation (mmHg)
    a. A-aD[O.sub.2] if Fi[O.sub.2]   <200
       [greater than or equal to]0.5
    b. Pa [O.sub.2] if Fi[O.sub.2]     >70          61-70
 6. Acid-base balance
    a. Arterial pH                       7.33-7.49             7.25-7.32
    b. Serum HC[O.sub.3] (mEq/l)        22-31.9               18-21.9
       if no arterial blood gas
 7. Sodium (mEq/l)                     130-149               120-129
 8. Potassium (mEq/l)                    3.5-5.4     3-3.4     2.5-2.9
 9. Creatinine (mg/dl)                   0.6-1.4              <0.6
10. Hematocirt (%)                      30-45.9               20-29.9
11. White blood count                    3-14.9                1-2.9
12. Glasgow Coma Score (GCS)

Physiologic Variable                     +3

 1. Temperature ([degrees]C)           30-31.9
 2. Mean arterial pressure (mmHg)
 3. Heart rate (/min)                  40-54
 4. Respiratory rate (/min)
 5. Oxygenation (mmHg)
    a. A-aD[O.sub.2] if Fi[O.sub.2]
       [greater than or equal to]0.5
    b. Pa [O.sub.2] if Fi[O.sub.2]     55-60
 6. Acid-base balance
    a. Arterial pH                      7.15-7.24
    b. Serum HC[O.sub.3] (mEq/l)       15-17.9
       if no arterial blood gas
 7. Sodium (mEq/l)                    111-119
 8. Potassium (mEq/l)
 9. Creatinine (mg/dl)
10. Hematocirt (%)
11. White blood count
12. Glasgow Coma Score (GCS)

Physiologic Variable                             +4

 1. Temperature ([degrees]C)           [less than or equal to]29.9
 2. Mean arterial pressure (mmHg)      [less than or equal to]49
 3. Heart rate (/min)                  [less than or equal to]39
 4. Respiratory rate (/min)             [less than or equal to]5
 5. Oxygenation (mmHg)
    a. A-aD[O.sub.2] if Fi[O.sub.2]
       [greater than or equal to]0.5
    b. Pa [O.sub.2] if Fi[O.sub.2]                           <55
 6. Acid-base balance
    a. Arterial pH                                            <7.15
    b. Serum HC[O.sub.3] (mEq/l)                             <15
       if no arterial blood gas
 7. Sodium (mEq/l)                    [less than or equal to]110
 8. Potassium (mEq/l)                                         <2.5
 9. Creatinine (mg/dl)
10. Hematocirt (%)                                            <2.5
11. White blood count                                         <1
12. Glasgow Coma Score (GCS)

A. Total Acute Physiology Score (sum of 12 above points)
B. Age points (years) [less than or equal to]44=0; 4 5 to 54 =2; 55 to
   64=3; 65 to 74=5; [greater than or equal to]75=6
C. Chronic Health Points (*)
Total APACHE II Score (add together the points from A+B+C)

(*) Chronic Health Points: If the patient has a history of severe organ
system insufficiency or is immune-compromised as defined below, assign
points as follows:
5 points for non-operative or emergency post-operative patients
2 points for elective post-operative patinets


There were 276 patients admitted to the neurosurgical ICU, mean age [+ or -] SD 47.94[+ or -]15.39 years. Of these, 246 (89.13%) were elective cases and 30 (10.87%) were emergency cases. Two hundred and ffty-eight (93.48%) patients were transferred from the operating theater, 12 (4.35%) from hospital ward, and six (2.17%) from outside the hospital. Demographics and patient characteristics are shown in Table 1.

Arterial blood gas analyses were performed completely in all 276 patients. Only two in the cerebral tumor and two in cerebral vascular lesion categories had received high concentration of oxygen (Fi[O.sub.2] >0.5), showing a mean A-a gradient of 178.85[+ or -]67.49 mm Hg. The incidence of acute renal failure and comorbidities indicating chronic health points, i.e. AIDS, hepatic failure, lymphoma, metastasis cancer, leukemia, immune compromise and cirrhosis were not identified. The APACHE II parameters are shown in Table 2.

There was no death at ICU discharge, while Glasgow Outcome Scale scores 2-5 (persistent vegetative state to good recovery) were recorded in one (0.36%), 14 (5.07%), 77 (27.90%) and 184 (66.67%) patients, respectively. At hospital discharge, 12 (4.35%) patients died. Of the 264 (95.65%) survivors, one (0.36%) had persistent vegetative state, seven (2.54%) were conscious but disabled, 42 (15.22%) were disabled but independent, and 214 (77.54%) had good recovery and were capable to return to their way of life. The overall APACHE II score in survivors and non survivors was 16.56[+ or -]5.95 (95% CI, 15.84-17.29) and 19.08[+ or -]6.47(95% CI, 15.40-22.76), while the calculated APACHE II adjusted predicted mortality was 13.39[+ or -]12.85% (95% CI, 11.83-14.95) and 17.49[+ or -] 13.51% (95% CI, 9.81-25.17), respectively. The APACHE II score and hospital mortality are summarized in Figure 2.

The AUC of APACHE II score to hospital mortality was 0.62 (95% CI, 0.44-0.79), as shown in Figure 3. Finally, the optimal cut point of 18 would yield the sensitivity of 58.33% (95% CI, 52.52-64.15) and specificity of 61.36% (95% CI, 55.62-67.11).

Seventeen patients had total length of hospital stay of over 114 days. The mean [+ or -] SD and median (minmax) for total length of hospital stay were 32.37[+ or -]65.57 days and 12 (2-535) days, while the mean [+ or -] SD and median (min-max) for the length of ICU stay were 2.55[+ or -]2.51 days and 2 (1-25) days, respectively.

The correlation of APACHE II score with the length of ICU stay ([r.sup.2]=0.12 with 95% CI 0.00-0.23; p=0.036) and length of hospital stay ([r.sup.2]=0.07 with 95% CI, 0.05-0.19; p=0.24) was nonsignificant.


This study demonstrated the severity of patient conditions in neurosurgical ICU in terms of APACHE II score, which probably reffects the spectrum of a tertiary referral neurosurgical center. Nevertheless, the mortality and length of hospital stay prediction was not achieved by APACHE II model.

For the performance of mortality prediction, the APACHE II scale has been validated and accepted in many settings of general ICU, with the AUC varying from 0.74 to 0.86 (17-21). The risk-adjusted formula to predict mortality estimated from APACHE II score is a remarkable advantage (18,19). The diagnostic category weight variables, e.g., the causes of respiratory failure, the causes of cardiovascular failure, the major vital organ surgeries leading to ICU admission post-surgery, type of surgery, etc., were included (4,22). However, the adjusted predicted values were not related to the observed mortality and could not discriminate between survivors and non-survivors in neurosurgical ICU. The possibility of monitoring modality, the effectiveness of multidisciplinary team, therapeutic preference and patient unique characteristics were considered, in particular patient distinctive nature, disease specific pathology, and severity of illness (23,24).

Besides the property of APACHE II score in mortality prediction, determining the length of hospitalization was also expected. This study showed a nonsignificant correlation between the scores and the length of hospital stay. Interestingly, even the length of ICU stay was longer than in an earlier study but when compared to general ICU, it was still shorter (25). This result is in contrast to the study by Rubiano et al., who report that the length of stay in teaching hospitals is longer because they need more time to investigate and take care specifically (26).

The practical reason that was different from the others was the primary patient condition. Most of the patients admitted to neurological ICU in this setting were healthy or were partially treated before their transfer. Ninety-three percent of the patients were admitted with the criterion of postoperative major neurosurgery without any other complications. In fact, the term 'High Dependency Care Unit' may be used properly instead of the term 'Intensive Care Unit' in these circumstances (27). Moreover, this unit has been organized as an open intensive care system. The responsible physician is a neurosurgeon appointed on the bed quota basis, which resulted in a lower and wider range of APACHE II scores (6-39 score of 0-67 total score).

Our study had several limitations. Firstly, we used an ICU to take care of postoperative patients that were healthy and most of them did not have any other complications. Despite this, the APACHE II score is less likely to represent the severity of the real situation. We would recommend re-estimation of the patients according to the admission criteria if applied to a national sample. Secondly, our hospital sample had a limited number of performance outliers because it is a tertiary referral healthcare center. There were a few cases of traumatic brain injury or emergency situation. A larger sample of cases is needed to draw more reliable conclusions in these circumstances. Thirdly, there was a limitation of the assessment frequency, as even the criteria of APACHE II evaluation were recommended to be measured once within 24 hours of admission but the estimated accuracy would be increased if the assessment could have been performed periodically.

In conclusion, the mean APACHE II score in neurosurgical ICU patients was 16.67[+ or -]5.99 (95% CI, 15.96-17.38). The calculated adjusted predicted mortality was 13.57[+ or -]12.88% (95% CI, 12.04-15.09), while the hospital-discharge mortality was only 4.35%. We found that the mortality predictive performance of APACHE II score was not precise. Nevertheless, these results can provide general informative data to the benefit of setting standard clinical indicators individually and initiate liberal study of the mortality predictor in these critical patients in the future.


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P. Akavipat, J. Tinkhamrop, B. Tinkhamrop i W. Sriraj

Sustav APACHE II. odobren je kao mjerilo i prediktor smrtnosti, no samo se nekoliko clanaka bavi njegovom primjenom kod neurokirurskih bolesnika. Stoga smo proveli ovo istrazivanje kako bismo potvrdili ovaj sustav i njegovu sposobnost predvidanja bolnicke smrtnosti u referentnoj tercijarnoj neurokirurskoj jedinici intenzivnog lijecenja (JIL). U istrazivanje su bili ukljuceni svi bolesnici primljeni u neurokirursku JIL od 1. veljace do 31. srpnja 2011. godine. Prikupljeni su podaci koji se odnose na parametre sustava APACHE II. Izracunat je prilagodeni rizik smrti i usporeden sa zabiljezenom stopom smrtnosti. U analizi je primijenjena deskriptivna statistika ukljucujuci ROC. Rezultati su pokazali da je primljeno 276 bolesnika. Zbir APACHE II. bio je 16,56 (95% CI, 15,84-17,29) za prezivjele i 19,08 (95% CI, 15,40-22,76) za umrle, dok je prilagodena predvidena stopa smrtnosti bila 13,39% (95% CI, 11,83-14,95) odnosno 17,49% (95% CI, 9,81-25,17). Zabiljezena stopa smrtnosti bila je samo 4,35%. Podrucje ispod ROC zbira APACHE II. za bolnicku smrtnost iznosila je 0,62 (95% CI, 0,44-0,79). U zakljucku, ne samo da je zbir APACHE II. pokazao nisku tezinu kod neurokirurskih bolesnika, nego je i njegov rezultat u predvidanju bolnicke smrtnosti bio nezadovoljavajuci. Treba provesti daljnja istrazivanja prediktora smrtnosti kod ovih kriticnih bolesnika.

Kljucne rijeci: APACHE; Bolnicka smrtnost; Duzina hospitalizacije; Stupanj tezine bolesti; Jedinice intenzivne skrbi

Phuping Akavipat (1), Jadsada Tinkhamrop (2), Bandit Tinkhamrop (3) and Wimonrat Sriraj (4)

(1) Anesthesiology Department, Prasat Neurological Institute, Bangkok, Tailand; (2) Department of Obstetrics and Gynecology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Tailand; (3) Department of Biostatistics and Demography, Faculty of Public Health, Khon Kaen University, Khon Kaen, Tailand; (4) Department of Anesthesiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Tailand

Correspondence to: Phuping Akavipat, MD, FRCAT, PhD, Anesthesiology Department, Prasat Neurological Institute, 312 Rajvithee Road, Bangkok 10400, Tailand


Received March 13, 2017, accepted January 23, 2019

doi: 10.20471/acc.2019.58.01.07
Table 1. Demographics and patient characteristics

Variable                             Number (%)

Sex: Male                            120 (43.5)
- Cerebral tumor                     201 (75.0)
- Cerebral aneurysm                   28 (10.1)
- Spondylosis                         11 (4.0)
- Spinal tumor                         4 (1.5)
- Others                              26 (9.4)
- Craniotomy with lesion removal     193 (69.9)
- Craniotomy with clipping aneurysm   24 (8.7)
- Spinal surgery                      15 (5.4)
- Others                              44 (15.9)
Reason for admission
- Major operation                    258 (93.5)
- Neurologic problems                 17 (6.2)
- Pulmonary problems                   1 (0.4)

Table 2. Values of Acute Physiology and Chronic Health Evaluation
(APACHE) II variables

Variable                          Number (%)   Mean [+ or -] SD

Temperature ([degrees]C)          276 (100)    36.47[+ or -]0.77
MAP (mm Hg)                       276 (100)   108.72[+ or -]22.43
Heart rate (/min)                 276 (100)    82.21[+ or -]16.66
RR (/min)                         276 (100)    18.22[+ or -]3.88
Pa[O.sub.2] (mm Hg)               276 (100)   200.74[+ or -]86.63
pH                                276 (100)     7.39[+ or -]0.07
Sodium (mEq/L)                    276 (100)   137.98[+ or -]3.83
Potassium (mEq/L)                 276 (100)     3.78[+ or -]0.43
Creatinine (mg/dL)                276 (100)     0.81[+ or -]0.33
Hematocrit (%)                    276 (100)    34.90[+ or -]4.70
WBC count (x[10.sup.3]/[micro]L)  276 (100)    14.10[+ or -]5.65
GCS (*)                           276 (100)    10.33[+ or -]3.63
Age (years)                                    47.94[+ or -]15.39
- [less than or equal to]44       120 (43.5)
- 45-54                            62 (22.5)
- 55-64                            52 (18.8)
- 65-74                            26 (9.4)
- [greater than or equal to]75     16 (5.8)

MAP = mean arterial pressure; RR = respiratory rate; GCS = Glasgow Coma
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Title Annotation:Original Scientific Paper
Author:Akavipat, Phuping; Tinkhamrop, Jadsada; Tinkhamrop, Bandit; Sriraj, Wimonrat
Publication:Acta Clinica Croatica
Date:Mar 1, 2019

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