Original Article
Full Outline of UnResponsiveness Score Versus Glasgow Coma Scale in Children With Nontraumatic Impairment of Consciousness
Journal of Child Neurology 2014, Vol. 29(10) 1299-1304 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073813514293 jcn.sagepub.com
Gurpreet Singh Kochar, DM1,2, Sheffali Gulati, MD3, Rakesh Lodha, MD4, and RM Pandey, PhD5
Abstract The study was designed to compare the Full Outline of UnResponsiveness score with Glasgow Coma Scale as a predictor of mortality and poor functional outcome at hospital discharge in children with nontraumatic impairment of consciousness. Seventy children aged 5 to 18 years admitted with impaired consciousness were enrolled. The scores were applied by the Pediatric Neurology fellow within 2 hours of admission. The primary outcome studied was in-hospital mortality. Receiver operating characteristic curves were used to compare the 2 scores. The area under the curves for Glasgow Coma Scale and Full Outline of UnResponsiveness scores were 0.916 and 0.940, respectively. However, the difference between the areas under curve for the 2 scores was not statistically significant (0.023; 95% confidence interval: –0.0115 to 0.058). Our data indicate that both the scores are good predictors for in-hospital mortality and functional outcome. However, no significant difference was observed between the ability of the 2 scores to predict the outcomes. Keywords Full Outline of UnResponsiveness (FOUR) score, Glasgow Coma Scale (GCS), coma, impaired consciousness Received August 27, 2013. Received revised September 04, 2013. Accepted for publication November 04, 2013.
The assessment of comatose patients is an important part of critical care. Further, the assessment of the level of coma relies on clinical scores. The Glasgow Coma Scale defined by Teasdale and Jennett in 19741 remains the most commonly used scoring system for altered state of consciousness. The unmodified Glasgow Coma Scale has been used in several series of pediatric traumatic coma, but there are considerable difficulties with the application of, particularly, the verbal scale in this age group. Various modifications for verbal components have been suggested in intubated patients. One of them is the grimace component of the modified Glasgow Coma Scale developed by Tatman et al,2 which appears to be more reliable than the verbal component. Although the Glasgow Coma Scale is the most widely used scale in adults as well as in children with impaired consciousness, it has many limitations. Many newer studies have found only moderate degrees of interrater agreement with Glasgow Coma Scale.3,4 The other major limitation is its inability to accurately assess intubated patients because of the requirement of a verbal component.5 Several methods have been used to circumvent this problem, such as pseudo-scoring6 (average of motor and eye score) and linear regression model7 (calculates predicted verbal response) and use of Grimace score,2 but none of these has been universally accepted. Also, Glasgow Coma Scale does not include
brainstem reflexes, which could reflect the severity of coma. Lastly, the score is skewed toward the motor part of the scale (6 items vs 4 for eyes and 5 for verbal). Summing the 3 subscales assumes equal weighting for each one, thus leading to loss of information since the same score can be made up in various ways.8 Considering the limitations of Glasgow Coma Scale, Wijdicks and colleagues9 in 2005 proposed a new coma scale named the Full Outline of UnResponsiveness score (Table 1).
1
Department of Pediatrics, Division of Pediatric Neurology, All India Institute of Medical Sciences, New Delhi, India 2 Department of Pediatric Neurology, SPS Apollo Hospital, Ludhiana (Punjab), India 3 Department of Pediatrics, Division of Pediatric Neurology, All India Institute of Medical Sciences, New Delhi, India 4 Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India 5 Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India Corresponding Author: Sheffali Gulati, MD, Department of Pediatrics, Division of Pediatric Neurology, All India Institute of Medical Sciences, New Delhi 110029, India. Email: [email protected]
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Table 1. Full Outline of UnResponsiveness Score.
Participants
Eye response 4 ¼ Eyelids open or opened, tracking or blinking to command 3 ¼ Eyelids open but not tracking 2 ¼ Eyelids closed but opens to loud voice 1 ¼ Eyelids closed but opens to pain 0 ¼ Eyelids remain closed with pain Motor response 4 ¼ Thumbs up, fist, or peace sign to command 3 ¼ Localizing to pain 2 ¼ Flexion response to pain 1 ¼ Extensor posturing 0 ¼ No response to pain or generalized myoclonus status epilepticus Brainstem reflexes 4 ¼ Pupil and corneal reflexes present 3 ¼ One pupil wide and fixed 2 ¼ Pupil or corneal reflexes absent 1 ¼ Pupil and corneal reflexes absent 0 ¼ Absent pupil, corneal, and cough reflex Respiration 4 ¼ Not intubated, regular breathing pattern 3 ¼ Not intubated, Cheyne-Stokes breathing pattern 2 ¼ Not intubated, irregular breathing pattern 1 ¼ Breathes above ventilator rate 0 ¼ Breathes at ventilator rate or apnea
Children aged 5 to 18 years who presented with impaired consciousness of less than 7 days’ duration and admitted in the pediatric ward or pediatric intensive care unit were eligible for inclusion. Children with traumatic brain injury, known vision/hearing impairment, cerebral palsy, intellectual disability, degenerative brain disease, and those already on sedatives or neuromuscular blockade and with ongoing seizures or seizures within the last 1 hour were excluded from the study.
The Full Outline of UnResponsiveness score has 4 testable components (E, eye responses; M, motor responses; B, brainstem reflexes; and R, respiration) in contrast to 3 components of the Glasgow Coma Scale. Each category is awarded 0 to 4 points, with 0 being the worst. As compared to the Glasgow Coma Scale, brainstem reflexes and respiration have been included whereas verbal response and withdrawal to pain (component of motor response) have been excluded from the Full Outline of UnResponsiveness score. The Full Outline of UnResponsiveness score has been validated by dedicated staff in a neurointensive care unit,10 nonneurology staff in emergency room,11 and intensive care unit staff of general intensive care units.12 There is limited experience for use of Full Outline of UnResponsiveness score in children. In a recent study in children with nontraumatic (predominantly brain tumors) and traumatic impairment of consciousness, the Full Outline of UnResponsiveness score has been found to be reliable and valid in predicting in-hospital mortality and poor outcome at discharge.13 In view of scant data in children and potential benefits of the Full Outline of UnResponsiveness score, we planned to compare this score with Glasgow Coma Scale in children aged 5 to 18 years admitted in the pediatric ward/intensive care unit with impaired consciousness as predictors of outcome (mortality and functional outcome at discharge).
Training of Investigator The investigator was trained with the standardized video examples included in a DVD prepared by the developers of the Full Outline of UnResponsiveness score (Wijdicks et al9). After training, the investigator demonstrated the score on 2 patients while being supervised by a senior pediatric neurologist.
Assessment Procedure All the observations (required for the Full Outline of UnResponsiveness score and Glasgow Coma Scale) and investigations (required for Paediatric Index of Mortality score, PIM2) are done routinely in the children admitted in the pediatric ward/ pediatric intensive care unit. Standardized care based on current guidelines was provided to all the patients. Rater carried one page hand-out with written instructions describing both the Full Outline of UnResponsiveness score and the Glasgow Coma Scale. Both the scores were applied by the rater within 2 hours of admission and before starting sedatives or neuromuscular blockade. In case the child was intubated before enrollment, the score on the Grimace scale2 was used as replacement for the verbal score on the Glasgow Coma Scale (5 ¼ spontaneous normal facial/oromotor activity, for example sucks tube, coughs; 4 ¼ less than usual spontaneous ability or only responds to touch; 3 ¼ vigorous grimace to pain; 2 ¼ mild grimace or some change in facial expression to pain; 1 ¼ no response to pain). The rater was the primary investigator in all the patients. The sequence of application of the scores was randomized using block randomization with block size of 10 patients. Severity of illness was assessed with the Paediatric Index of Mortality score,14 for which the values of various variables at time of were recorded. The children with impaired consciousness and reduced mental state were classified as obtunded, stuporous, or comatose based on the classification by Taylor et al.15 The etiology was determined based on a review of the clinical, laboratory, and imaging data by the senior pediatric neurologist. The patient was observed till discharge or in-hospital mortality. The functional outcome of the patients was assessed by the Pediatric Overall Performance Category (POPC)16 at the time of pediatric intensive care unit discharge or 1 month following admission, whichever was earlier. Children were considered to have poor outcomes if they scored 3 to 6 on the Pediatric Overall Performance Category scale, consistent with moderate to severe disability to vegetative state, coma, or brain death.
Methods
Quality Assurance
This prospective observational study was carried out from May 2009 to June 2010 in the Department of Pediatrics, All India Institute of Medical Sciences, New Delhi.
There was periodic training of the investigator every month by reviewing the case examples in DVD and rechecking the score in every fifth child by the senior pediatric neurologist.
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Outcome Measures The primary outcome studied was in-hospital mortality. The secondary outcome was functional outcome at discharge as assessed by the POPC scale. The predictive ability of the 2 scores was compared by calculating area under the curve (AUC) using a receiver operating characteristic (ROC) curve.
Sample Size Estimation and Statistical Analysis From the previous studies, it is known that the area under the receiver operating characteristic curve of the Glasgow Coma Scale score in children for prediction of mortality is 0.7 to 0.9.17 Assuming area under the receiver operating characteristic curve of Glasgow Coma Scale to be 0.85 and Full Outline of UnResponsiveness score to be a better predictor of outcome (area under the curve for Full Outline of UnResponsiveness score assumed to be 0.95), the sample size calculation was done using MedcalcR version 9.2.0.1. The correlation between both the scores and outcome was assumed to be 0.7. Keeping the a-level as 0.05 and b-level as 0.20, the sample size was calculated to be 80 (40 in each group). We could recruit 70 patients during the study period. Data were analyzed by SPSS 15.0 for Windows (SPSS Inc, Chicago, IL) and receiver operating characteristic curve analyses were performed. The predictive value of the Glasgow Coma Scale and Full Outline of UnResponsiveness scores in predicting primary outcome measures was established using the receiver operating characteristic curve by calculating the area under the curve. This study was approved by the institutional ethics committee. Written informed consent was obtained from the parents/guardians for all patients.
Results During the study period, 90 patients meeting inclusion criteria were assessed for eligibility. Of these, 20 patients were excluded (6 patients already on sedatives or neuromuscular blockade, 4 children had cerebral palsy, 5 had degenerative brain disease, and 5 patients had status epilepticus and ongoing seizures). Thus, a total of 70 patients were included in the study. The median age of the patients was 8 years (range 5-16 years). Of 70 patients, 46 (65.7%) were boys and 24 were girls (34.3%). The median duration of symptoms at presentation was 24 hours. Most common presenting symptoms were fever seen in 49 (70%) of the cases, convulsions (59%), headache (46%), vomiting (46%), and behavioral change (53%). Of 70 children, 18 each were classified (as per classification given by Taylor et al15) as obtunded and stuporous (25.7% each) and 34 were comatose (48.6%). The mean percentage predicted mortality using the Pediatric Index of Mortality score in 70 patients was 24.2% + 29.02%. Central nervous system infections accounted for 38 (54.3%) of cases (Table 2). Among the other 32 children, most common diagnoses were fulminant hepatic failure and intracranial bleed secondary to underlying bleeding diathesis. Underlying chronic illness was observed in 36 (51.5%) patients. The most common underlying disease was cyanotic congenital heart disease.
Table 2. Etiological Diagnosis in 70 Children With Impaired Consciousness. Diagnosis CNS infections Meningo-encephalitis Tuberculous meningitis Acute bacterial meningitis Multiple neurocysticercosis Brain abscess Enteric encephalopathy Cerebral malaria Dengue encephalopathy Meningococcemia Rabies encephalitis ADEM Acute febrile encephalopathy, unspecified Total Noninfectious causes Fulminant hepatic failure IC bleed Postcardiac surgery HIE Uremic encephalopathy DKA Hypertensive encephalopathy Other/unknown Total
n (%) 12 (17.1) 7 (10) 2 (2.9) 1 (1.4) 5 (7.1) 2 (2.9) 1 (1.4) 1 (1.4) 1 (1.4) 1 (1.4) 2 (2.9) 3 (4.3) 38 (54.3) 9 (12.9) 8 (11.4) 4 (5.7) 3 (4.3) 1 (1.4) 3 (4.3) 4 (5.7) 32 (45.7)
Abbreviations: ADEM, acute disseminated encephalomyelitis; CNS, central nervous system; DKA, diabetic ketoacidosis; HIE, hypoxic-ischemic encephalopathy; IC, internal carotid.
Forty-four of 70 patients required ventilation (62.9%). The median (IQR) duration of ventilation was 5 (3-8.75) days. Twenty-six patients were already intubated at the time of evaluation. Of 70 patients, 38 (54.3%) survived and 32 (45.7%) died. The mortality rate for central nervous system infections was 37% and for toxic metabolic group was 45%.
Performance of Glasgow Coma Scale and Full Outline of UnResponsiveness Score in Predicting Mortality The mean total Glasgow Coma score was 7.93 + 3.4 (median ¼ 8, interquartile range ¼ 8-10.25) and the mean total Full Outline of UnResponsiveness score was 9.77 + 4.74 (median ¼ 10, interquartile range ¼ 7-14). In our population, both Glasgow Coma Scale and Full Outline of UnResponsiveness score discriminated well between death and survival, the area under the curve values for Glasgow Coma Scale and Full Outline of UnResponsiveness score were 0.916 (95% confidence interval: 0.825-0.969) and 0.940 (95% confidence interval: 0.8560.982), respectively, (Figure 1). The difference between the areas under curve for Glasgow Coma Scale and Full Outline of UnResponsiveness score was not statistically significant (0.023; 95% confidence interval ¼ –0.0115 to 0.058, P value ¼ .118). The area under the curve values in 26 patients who were already intubated at the time of application of scores were 0.971 (0.818-1.00) and 0.900 (0.718-0.982), respectively,
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Journal of Child Neurology 29(10) Table 3. Receiver Operating Characteristic Curve Analyses in Predicting Hospital Mortality and Poor Functional Outcome for FOUR Score, GCS, and Subunit Scores.
Figure 1. Area under the curve values for the Full Outline of UnResponsiveness score and the Glasgow Coma Scale for in-hospital mortality (left) and poor functional outcome (Pediatric Overall Performance Category score 3-6) (right). Abbreviations: FOUR, Full Outline of UnResponsiveness; GCS, Glasgow Coma Scale.
for the Full Outline of UnResponsivess score and Glasgow Coma Scale. The cut-off value with maximum sensitivity and specificity was obtained by the receiver operating characteristic curves. The cut-off for the Full Outline of UnResponsiveness score in predicting mortality was 10 and for Glasgow Coma Scale was 8. The sensitivity and specificity of the Full Outline of UnResponsiveness score 10 in predicting mortality were both 81%; the Positive and Negative predictive values were 79% and 84%, respectively. The sensitivity and specificity of Glasgow Coma Scale score 8 in predicting the mortality was 90% and 74%, respectively. The positive and the negative predictive values were 78% and 84%, respectively.
Functional Outcome at Discharge: Pediatric Overall Performance Category Score Of 38 survivors, 20 (52.6%) were categorized into good outcome and 18 (47.4%) were categorized having poor functional outcome at discharge. The area under the curve values predicting poor functional outcome at discharge (Pediatric Overall Performance Category score 3-6) for Glasgow Coma Scale was 0.732 (95% confidence interval: 0.564-0.862) and that for Full Outline of UnResponsiveness score was 0.746 (95% confidence interval: 0.579-0.873) (Figure 1). The difference between the areas under the curve for Glasgow Coma Scale and Full Outline of UnResponsiveness score was not statistically significant (0.013; 95% confidence interval: –0.06 to 0.09). The results indicate that both Glasgow Coma Scale and Full Outline of UnResponsiveness score are good predictors for poor functional outcome at discharge and Full Outline of UnResponsiveness score is not observed to be superior to Glasgow Coma Scale in predicting the poor functional outcome. The subunit analysis of Full Outline of UnResponsiveness score revealed that brainstem subscore had a lower area under
Total FOUR score FOUR score eye FOUR score motor FOUR score brainstem FOUR score respiration GCS total GCS eye GCS motor GCS verbal
Area under the curve (95% CI) for mortality
Area under the curve (95% CI) for poor outcome
0.940 (0.889-0.990) 0.857 (0.769-0.946) 0.896 (0.823-0.969) 0.716 (0.590-0.842) 0.865 (0.773-0.956) 0.916 (0.855-0.978) 0.830 (0.734-0.926) 0.896 (0.822-0.969) 0.786 (0.678-0.893)
0.746 (0.584-0.908) 0.706 (0.538-0.873) 0.606 (0.425-0.786) 0.611 (0.428-0.794) 0.638 (0.457-0.818) 0.732 (0.568-0.896) 0.612 (0.431-0.794) 0.789 (0.635-0.943) 0.660 (0.474-0.845)
Abbreviations: CI, confidence interval; FOUR, Full Outline of UnResponsiveness; GCS, Glasgow Coma Scale.
the curve value than eye, motor, and respiration components and total scores of Glasgow Coma Scale and the Full Outline of UnResponsiveness score had higher area under the curve values than subunit scores (Table 3). The odds ratio for mortality prediction with total Full Outline of UnResponsiveness score and total Glasgow Coma Scale was calculated by logistic regression analysis. After adjusting for age, duration of symptoms, need for ventilation and severity of illness (Pediatric Index of Mortality score), the odds ratio for total Full Outline of UnResponsiveness score was 0.53; that is for every 1-point increase in Full Outline of UnResponsiveness score, there is 47% reduction in odds of mortality. Similarly, the adjusted odds ratio for the Glasgow Coma Scale score was 0.48 implicating that for every 1-point increase in total Glasgow Coma Scale score, there is 52% reduction in odds of mortality. In the logistic regression model, Full Outline of UnResponsiveness score, Glasgow Coma Scale score, and Pediatric Index of Mortality were found to be independent predictors of mortality.
Discussion The results from the current study demonstrate the feasibility of use of the Full Outline of UnResponsiveness score in pediatric patients with nontraumatic impairment of consciousness and good predictive value for in-hospital mortality and functional outcome at discharge. Children more than 5 years were recruited as there was no experience of the Full Outline of UnResponsiveness score in children less than 5 years at the start of the study and the eye and motor components of the score require some patient cooperation. Cohen et al13 found the score feasible to apply and reliable in children as young as 2 years of age. Thus, this score can be applied in younger populations and can be tested in our setting in further studies. The results are consistent with other adult studies and a pediatric study. In the only other pediatric study13 in 60 children, 35 pediatric critical care nurse raters participated and it was demonstrated that
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for in-hospital mortality, the area under the curve for the Full Outline of UnResponsiveness was 0.81 and that for the Glasgow Coma Scale score was 0.77. As in the current study, the differences in area under the curve values were not statistically significant. In a pooled analysis comprising 381 adult patients,18 the area under the curve for the total Full Outline of UnResponsiveness score was 0.88, and for the Glasgow Coma Scale scores the area under the curve was 0.87. The Full Outline of UnResponsiveness score provided additional information with respect to survival in the most severe cases (Glasgow Coma Scale score of 3). In the current study, the area under the curve values were higher than those obtained in previously published validation studies.9-13 The adjusted odds ratio for both the scores (0.52 for Full Outline of UnResponsiveness score and 0.48 for Glasgow Coma Scale) were lower compared with previous studies, implicating higher positive predictive value for survival with increasing scores. As there was a single rater in the present study who applied the scores and periodic check of the scores applied by a senior pediatric neurologist, this might have resulted in higher area under the curve values for both the scores. Outside the Mayo Clinic, the Full Outline of UnResponsiveness score has been validated in other countries with Italian,20 Spanish,21 and French22 versions. Marcati and colleagues20 found the score to be reliable, valid, practical, and accurate as a prognostic indicator. The area under the curve value for mortality in their study was 0.935 for the Full Outline of UnResponsiveness and 0.953 for the Glasgow Coma Scale. Thus, the new scale consistently demonstrates high predictive value and good interrater agreement and is practical to use. Being a new score, there are few criticisms of the Full Outline of UnResponsiveness score. A few studies outside the Mayo Clinic have found inclusion of brainstem and respiration components in the Full Outline of UnResponsiveness score to be not sufficient enough for replacing the Glasgow Coma Scale in clinical practice. In a study comparing Glasgow Coma Scale and Full Outline of UnResponsiveness score in emergency setting, Eken et al23 enrolled 185 patients older than 17 years who presented with an altered level of consciousness after head trauma or with neurologic complaints. Area under the curve values in predicting hospital mortality for Glasgow Coma Scale and Full Outline of UnResponsiveness score were 0.735 and 0.788, respectively. The area under the curve value of brainstem and respiration component was 0.598 and 0.585, respectively. The authors concluded that Full Outline of UnResponsiveness Score was not superior to the Glasgow Coma Scale as the brainstem reflexes and respiratory pattern did not provide the expected benefit to using the eye and motor components. In another study, Fischer and colleagues24 observed that the interrater reliability for the Full Outline of UnResponsiveness score was at least as good as that of the Glasgow Coma Scale and they found the Full Outline of UnResponsiveness score to be superior to the Glasgow Coma Scale with regard to exact interrater agreement. They demonstrated that the interrater agreement was lowest for the ‘‘brainstem’’ component. Although the new Full Outline of UnResponsiveness score has many advantages over the Glasgow Coma Scale as stated
above, the difference between the areas under the curve for Glasgow Coma Scale and Full Outline of UnResponsiveness scores was not statistically significant as in most other studies. But this does not completely negate the benefits of the Full Outline of UnResponsiveness score. Rather, the present study forms the basis for feasibility of further longitudinal studies to compare Glasgow Coma Scale and Full Outline of UnResponsiveness scores in children for serial monitoring of patients and to examine if the above-mentioned advantages of the Full Outline of UnResponsiveness score aid in better monitoring and decision making in treatment of the patients. Moreover, patients with the lowest Glasgow Coma Scale score (3-5) had Full Outline of UnResponsiveness score values between 0 and 8, emphasizing that the latter provides more neurologic detail in severely affected patients and might be more useful than the Glasgow Coma Scale score in tracking the clinical status of patients. The lower area under the curve values of the brainstem component of the Full Outline of UnResponsiveness score in the present study (0.716) demonstrate that it does not provide the expected benefit to using eye and motor components of the score. Nevertheless, the brainstem component may prove to be useful in careful monitoring of the children. This is one of the first few studies evaluating the Full Outline of UnResponsiveness score in children with nontraumatic impairment of consciousness. At the time of initiation of the present study, there were no published studies in pediatric patients. Second, we had measures for proper training of the investigator by use of videos and periodic cross checking by the pediatric neurologist. Lastly, the outcomes used are objective and the functional outcome measure (Pediatric Overall Performance Category) was used at discharge, which has been validated for pediatric patients. The limitation of the study was that a single rater performed both scores and thus the interrater reliability could not be tested. Another limitation is that the sample size was calculated estimating the area under the curve for Glasgow Coma Scale score as 0.8; in the present study, we observed area under the curve as 0.916. So, the study was under-powered to detect the statistically significant advantage of Full Outline of UnResponsiveness score.
Conclusion Both Glasgow Coma Score and Full Outline of UnResponsiveness score are good predictors for in-hospital mortality and functional outcome at discharge in children with nontraumatic impairment of consciousness. No significant difference was observed between the ability of the 2 scores to predict the mortality and functional outcome at discharge. For assessing other properties of an ideal coma score, further studies need to be carried out to assess interrater agreement and predictive validity and accuracy of scores done by nursing staff and intensive care unit residents. Acknowledgments The work was performed at the All India Institute of Medical Sciences (AIIMS), New Delhi, India.
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Author Contributions All authors contributed to the content of the manuscript. GSK was the principal investigator and did the clinical evaluation and scoring of all the children, reviewed the literature, and prepared the manuscript. RL contributed to designing and conceptualizing the study, supervised the data collection, and helped in drafting the manuscript and data analysis. RMP performed the analysis and interpretation of the data. SG was overall in charge of the case; trained the investigator (GSK), supervised the data collection, did periodic reevaluation of the investigator, and approved the final version of the manuscript.
Declaration of Conflicting Interests The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The authors received no financial support for the research, authorship, and/or publication of this article.
Ethical Approval This study was approved by institutional ethics committee, All India Institute of Medical Sciences New Delhi, India (T-17/01.05.09). Written informed consent was obtained from the parents/guardians for all patients.
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9. Prasad K. The Glasgow Coma Scale: a critical appraisal of its clinimetric properties. J Clin Epidemiol. 1996;49:755-763. 10. Wijdicks EFM, Bamlet WR, Maramattom BV, Manno EM, McClelland RL. Validation of new coma scale: the FOUR score. Ann Neurol. 2005;58:585-593. 11. Wolf CA, Wijdicks EFM, Bamlet WR, McClelland RL. Further validation of the FOUR score coma scale by intensive care nurses. Mayo Clin Proc. 2007;82:435-438. 12. Stead LG, Wijdicks EFM, Bhagra A, et al. Validation of a new coma scale, the FOUR score in the emergency department. Neurol Crit Care. 2009;10:50-54. 13. Iyer VN, Mandrekar JN, Danielson RD, Zubkov AY, Elmer JL, Wijdicks EF. Validity of the FOUR score coma scale in the medical intensive care unit. Mayo Clin Proc. 2009;84:694-701. 14. Cohen J. Interrater reliability and predictive validity of FOUR score coma scale in paediatric population. J Neurosci Nurs. 2009;41:261-269. 15. Slater A, Shann F, Pearson G. Paediatric Index of Mortality (PIM) Study Group. PIM2: a revised version of the Paediatric Index of Mortality. Intensive Care Med. 2003;29:278-285. 16. Taylor DA, Ashwal S. Impairment of consciousness and coma. In: Swaiman KF, ed. Pediatric Neurology: Principles and Practice. 4th ed. Philadelphia, PA: Elsevier (Mosby) 2006. 17. Fiser DH. Assessing the outcome of pediatric intensive care. J Pediatr. 1992;121:68-74. 18. Grinkevici¯ute DE, Kevalas R, Saferis V, Matukevicius A, Ragaisis V, Tamasauskas A. Predictive value of scoring system in severe pediatric head injury. Medicina (Kaunas). 2007;43:861-869. 19. Wijdicks EF, Rabinstein AA, Bamlet WR, Mandrekar JN. FOUR score and Glasgow Coma Scale in predicting outcome of comatose patients: a pooled analysis. Neurology. 2011;77: 84-85. 20. Marcati E, Ricci S, Casalena A, Toni D, Carolei A, Sacco S. Validation of the Italian version of a new coma scale: the FOUR score. Intern Emerg Med. 2012;7:145-152. 21. Idrovo L, Fuentes B, Medina J, et al. Validation of the FOUR Score (Spanish Version) in acute stroke: an inter-observer variability study. Eur Neurol. 2010;63:364-369. 22. Weiss N, Mutlu G, Essardy F, et al. The French version of the FOUR score: a new coma score. Rev Neurol. 2009;165: 796-802. 23. Eken C, Kartal M, Bacanli A, Eray O. Comparison of the Full Outline of Unresponsiveness Score Coma Scale and the Glasgow Coma Scale in an emergency setting population. Eur J Emerg Med. 2008;16:29-36. 24. Fischer M, Ru¨egg S, Czaplinski A, et al. Inter-rater reliability of the Full Outline of UnResponsiveness score and the Glasgow Coma Scale in critically ill patients: a prospective observational study. Crit Care. 2010;14:R64.
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Full Outline of UnResponsiveness Score Versus Glasgow Coma Scale in Children With Nontraumatic Impairment of Consciousness
Journal of Child Neurology 2014, Vol. 29(10) 1299-1304 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073813514293 jcn.sagepub.com
Gurpreet Singh Kochar, DM1,2, Sheffali Gulati, MD3, Rakesh Lodha, MD4, and RM Pandey, PhD5
Abstract The study was designed to compare the Full Outline of UnResponsiveness score with Glasgow Coma Scale as a predictor of mortality and poor functional outcome at hospital discharge in children with nontraumatic impairment of consciousness. Seventy children aged 5 to 18 years admitted with impaired consciousness were enrolled. The scores were applied by the Pediatric Neurology fellow within 2 hours of admission. The primary outcome studied was in-hospital mortality. Receiver operating characteristic curves were used to compare the 2 scores. The area under the curves for Glasgow Coma Scale and Full Outline of UnResponsiveness scores were 0.916 and 0.940, respectively. However, the difference between the areas under curve for the 2 scores was not statistically significant (0.023; 95% confidence interval: –0.0115 to 0.058). Our data indicate that both the scores are good predictors for in-hospital mortality and functional outcome. However, no significant difference was observed between the ability of the 2 scores to predict the outcomes. Keywords Full Outline of UnResponsiveness (FOUR) score, Glasgow Coma Scale (GCS), coma, impaired consciousness Received August 27, 2013. Received revised September 04, 2013. Accepted for publication November 04, 2013.
The assessment of comatose patients is an important part of critical care. Further, the assessment of the level of coma relies on clinical scores. The Glasgow Coma Scale defined by Teasdale and Jennett in 19741 remains the most commonly used scoring system for altered state of consciousness. The unmodified Glasgow Coma Scale has been used in several series of pediatric traumatic coma, but there are considerable difficulties with the application of, particularly, the verbal scale in this age group. Various modifications for verbal components have been suggested in intubated patients. One of them is the grimace component of the modified Glasgow Coma Scale developed by Tatman et al,2 which appears to be more reliable than the verbal component. Although the Glasgow Coma Scale is the most widely used scale in adults as well as in children with impaired consciousness, it has many limitations. Many newer studies have found only moderate degrees of interrater agreement with Glasgow Coma Scale.3,4 The other major limitation is its inability to accurately assess intubated patients because of the requirement of a verbal component.5 Several methods have been used to circumvent this problem, such as pseudo-scoring6 (average of motor and eye score) and linear regression model7 (calculates predicted verbal response) and use of Grimace score,2 but none of these has been universally accepted. Also, Glasgow Coma Scale does not include
brainstem reflexes, which could reflect the severity of coma. Lastly, the score is skewed toward the motor part of the scale (6 items vs 4 for eyes and 5 for verbal). Summing the 3 subscales assumes equal weighting for each one, thus leading to loss of information since the same score can be made up in various ways.8 Considering the limitations of Glasgow Coma Scale, Wijdicks and colleagues9 in 2005 proposed a new coma scale named the Full Outline of UnResponsiveness score (Table 1).
1
Department of Pediatrics, Division of Pediatric Neurology, All India Institute of Medical Sciences, New Delhi, India 2 Department of Pediatric Neurology, SPS Apollo Hospital, Ludhiana (Punjab), India 3 Department of Pediatrics, Division of Pediatric Neurology, All India Institute of Medical Sciences, New Delhi, India 4 Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India 5 Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India Corresponding Author: Sheffali Gulati, MD, Department of Pediatrics, Division of Pediatric Neurology, All India Institute of Medical Sciences, New Delhi 110029, India. Email: [email protected]
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Table 1. Full Outline of UnResponsiveness Score.
Participants
Eye response 4 ¼ Eyelids open or opened, tracking or blinking to command 3 ¼ Eyelids open but not tracking 2 ¼ Eyelids closed but opens to loud voice 1 ¼ Eyelids closed but opens to pain 0 ¼ Eyelids remain closed with pain Motor response 4 ¼ Thumbs up, fist, or peace sign to command 3 ¼ Localizing to pain 2 ¼ Flexion response to pain 1 ¼ Extensor posturing 0 ¼ No response to pain or generalized myoclonus status epilepticus Brainstem reflexes 4 ¼ Pupil and corneal reflexes present 3 ¼ One pupil wide and fixed 2 ¼ Pupil or corneal reflexes absent 1 ¼ Pupil and corneal reflexes absent 0 ¼ Absent pupil, corneal, and cough reflex Respiration 4 ¼ Not intubated, regular breathing pattern 3 ¼ Not intubated, Cheyne-Stokes breathing pattern 2 ¼ Not intubated, irregular breathing pattern 1 ¼ Breathes above ventilator rate 0 ¼ Breathes at ventilator rate or apnea
Children aged 5 to 18 years who presented with impaired consciousness of less than 7 days’ duration and admitted in the pediatric ward or pediatric intensive care unit were eligible for inclusion. Children with traumatic brain injury, known vision/hearing impairment, cerebral palsy, intellectual disability, degenerative brain disease, and those already on sedatives or neuromuscular blockade and with ongoing seizures or seizures within the last 1 hour were excluded from the study.
The Full Outline of UnResponsiveness score has 4 testable components (E, eye responses; M, motor responses; B, brainstem reflexes; and R, respiration) in contrast to 3 components of the Glasgow Coma Scale. Each category is awarded 0 to 4 points, with 0 being the worst. As compared to the Glasgow Coma Scale, brainstem reflexes and respiration have been included whereas verbal response and withdrawal to pain (component of motor response) have been excluded from the Full Outline of UnResponsiveness score. The Full Outline of UnResponsiveness score has been validated by dedicated staff in a neurointensive care unit,10 nonneurology staff in emergency room,11 and intensive care unit staff of general intensive care units.12 There is limited experience for use of Full Outline of UnResponsiveness score in children. In a recent study in children with nontraumatic (predominantly brain tumors) and traumatic impairment of consciousness, the Full Outline of UnResponsiveness score has been found to be reliable and valid in predicting in-hospital mortality and poor outcome at discharge.13 In view of scant data in children and potential benefits of the Full Outline of UnResponsiveness score, we planned to compare this score with Glasgow Coma Scale in children aged 5 to 18 years admitted in the pediatric ward/intensive care unit with impaired consciousness as predictors of outcome (mortality and functional outcome at discharge).
Training of Investigator The investigator was trained with the standardized video examples included in a DVD prepared by the developers of the Full Outline of UnResponsiveness score (Wijdicks et al9). After training, the investigator demonstrated the score on 2 patients while being supervised by a senior pediatric neurologist.
Assessment Procedure All the observations (required for the Full Outline of UnResponsiveness score and Glasgow Coma Scale) and investigations (required for Paediatric Index of Mortality score, PIM2) are done routinely in the children admitted in the pediatric ward/ pediatric intensive care unit. Standardized care based on current guidelines was provided to all the patients. Rater carried one page hand-out with written instructions describing both the Full Outline of UnResponsiveness score and the Glasgow Coma Scale. Both the scores were applied by the rater within 2 hours of admission and before starting sedatives or neuromuscular blockade. In case the child was intubated before enrollment, the score on the Grimace scale2 was used as replacement for the verbal score on the Glasgow Coma Scale (5 ¼ spontaneous normal facial/oromotor activity, for example sucks tube, coughs; 4 ¼ less than usual spontaneous ability or only responds to touch; 3 ¼ vigorous grimace to pain; 2 ¼ mild grimace or some change in facial expression to pain; 1 ¼ no response to pain). The rater was the primary investigator in all the patients. The sequence of application of the scores was randomized using block randomization with block size of 10 patients. Severity of illness was assessed with the Paediatric Index of Mortality score,14 for which the values of various variables at time of were recorded. The children with impaired consciousness and reduced mental state were classified as obtunded, stuporous, or comatose based on the classification by Taylor et al.15 The etiology was determined based on a review of the clinical, laboratory, and imaging data by the senior pediatric neurologist. The patient was observed till discharge or in-hospital mortality. The functional outcome of the patients was assessed by the Pediatric Overall Performance Category (POPC)16 at the time of pediatric intensive care unit discharge or 1 month following admission, whichever was earlier. Children were considered to have poor outcomes if they scored 3 to 6 on the Pediatric Overall Performance Category scale, consistent with moderate to severe disability to vegetative state, coma, or brain death.
Methods
Quality Assurance
This prospective observational study was carried out from May 2009 to June 2010 in the Department of Pediatrics, All India Institute of Medical Sciences, New Delhi.
There was periodic training of the investigator every month by reviewing the case examples in DVD and rechecking the score in every fifth child by the senior pediatric neurologist.
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Outcome Measures The primary outcome studied was in-hospital mortality. The secondary outcome was functional outcome at discharge as assessed by the POPC scale. The predictive ability of the 2 scores was compared by calculating area under the curve (AUC) using a receiver operating characteristic (ROC) curve.
Sample Size Estimation and Statistical Analysis From the previous studies, it is known that the area under the receiver operating characteristic curve of the Glasgow Coma Scale score in children for prediction of mortality is 0.7 to 0.9.17 Assuming area under the receiver operating characteristic curve of Glasgow Coma Scale to be 0.85 and Full Outline of UnResponsiveness score to be a better predictor of outcome (area under the curve for Full Outline of UnResponsiveness score assumed to be 0.95), the sample size calculation was done using MedcalcR version 9.2.0.1. The correlation between both the scores and outcome was assumed to be 0.7. Keeping the a-level as 0.05 and b-level as 0.20, the sample size was calculated to be 80 (40 in each group). We could recruit 70 patients during the study period. Data were analyzed by SPSS 15.0 for Windows (SPSS Inc, Chicago, IL) and receiver operating characteristic curve analyses were performed. The predictive value of the Glasgow Coma Scale and Full Outline of UnResponsiveness scores in predicting primary outcome measures was established using the receiver operating characteristic curve by calculating the area under the curve. This study was approved by the institutional ethics committee. Written informed consent was obtained from the parents/guardians for all patients.
Results During the study period, 90 patients meeting inclusion criteria were assessed for eligibility. Of these, 20 patients were excluded (6 patients already on sedatives or neuromuscular blockade, 4 children had cerebral palsy, 5 had degenerative brain disease, and 5 patients had status epilepticus and ongoing seizures). Thus, a total of 70 patients were included in the study. The median age of the patients was 8 years (range 5-16 years). Of 70 patients, 46 (65.7%) were boys and 24 were girls (34.3%). The median duration of symptoms at presentation was 24 hours. Most common presenting symptoms were fever seen in 49 (70%) of the cases, convulsions (59%), headache (46%), vomiting (46%), and behavioral change (53%). Of 70 children, 18 each were classified (as per classification given by Taylor et al15) as obtunded and stuporous (25.7% each) and 34 were comatose (48.6%). The mean percentage predicted mortality using the Pediatric Index of Mortality score in 70 patients was 24.2% + 29.02%. Central nervous system infections accounted for 38 (54.3%) of cases (Table 2). Among the other 32 children, most common diagnoses were fulminant hepatic failure and intracranial bleed secondary to underlying bleeding diathesis. Underlying chronic illness was observed in 36 (51.5%) patients. The most common underlying disease was cyanotic congenital heart disease.
Table 2. Etiological Diagnosis in 70 Children With Impaired Consciousness. Diagnosis CNS infections Meningo-encephalitis Tuberculous meningitis Acute bacterial meningitis Multiple neurocysticercosis Brain abscess Enteric encephalopathy Cerebral malaria Dengue encephalopathy Meningococcemia Rabies encephalitis ADEM Acute febrile encephalopathy, unspecified Total Noninfectious causes Fulminant hepatic failure IC bleed Postcardiac surgery HIE Uremic encephalopathy DKA Hypertensive encephalopathy Other/unknown Total
n (%) 12 (17.1) 7 (10) 2 (2.9) 1 (1.4) 5 (7.1) 2 (2.9) 1 (1.4) 1 (1.4) 1 (1.4) 1 (1.4) 2 (2.9) 3 (4.3) 38 (54.3) 9 (12.9) 8 (11.4) 4 (5.7) 3 (4.3) 1 (1.4) 3 (4.3) 4 (5.7) 32 (45.7)
Abbreviations: ADEM, acute disseminated encephalomyelitis; CNS, central nervous system; DKA, diabetic ketoacidosis; HIE, hypoxic-ischemic encephalopathy; IC, internal carotid.
Forty-four of 70 patients required ventilation (62.9%). The median (IQR) duration of ventilation was 5 (3-8.75) days. Twenty-six patients were already intubated at the time of evaluation. Of 70 patients, 38 (54.3%) survived and 32 (45.7%) died. The mortality rate for central nervous system infections was 37% and for toxic metabolic group was 45%.
Performance of Glasgow Coma Scale and Full Outline of UnResponsiveness Score in Predicting Mortality The mean total Glasgow Coma score was 7.93 + 3.4 (median ¼ 8, interquartile range ¼ 8-10.25) and the mean total Full Outline of UnResponsiveness score was 9.77 + 4.74 (median ¼ 10, interquartile range ¼ 7-14). In our population, both Glasgow Coma Scale and Full Outline of UnResponsiveness score discriminated well between death and survival, the area under the curve values for Glasgow Coma Scale and Full Outline of UnResponsiveness score were 0.916 (95% confidence interval: 0.825-0.969) and 0.940 (95% confidence interval: 0.8560.982), respectively, (Figure 1). The difference between the areas under curve for Glasgow Coma Scale and Full Outline of UnResponsiveness score was not statistically significant (0.023; 95% confidence interval ¼ –0.0115 to 0.058, P value ¼ .118). The area under the curve values in 26 patients who were already intubated at the time of application of scores were 0.971 (0.818-1.00) and 0.900 (0.718-0.982), respectively,
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Journal of Child Neurology 29(10) Table 3. Receiver Operating Characteristic Curve Analyses in Predicting Hospital Mortality and Poor Functional Outcome for FOUR Score, GCS, and Subunit Scores.
Figure 1. Area under the curve values for the Full Outline of UnResponsiveness score and the Glasgow Coma Scale for in-hospital mortality (left) and poor functional outcome (Pediatric Overall Performance Category score 3-6) (right). Abbreviations: FOUR, Full Outline of UnResponsiveness; GCS, Glasgow Coma Scale.
for the Full Outline of UnResponsivess score and Glasgow Coma Scale. The cut-off value with maximum sensitivity and specificity was obtained by the receiver operating characteristic curves. The cut-off for the Full Outline of UnResponsiveness score in predicting mortality was 10 and for Glasgow Coma Scale was 8. The sensitivity and specificity of the Full Outline of UnResponsiveness score 10 in predicting mortality were both 81%; the Positive and Negative predictive values were 79% and 84%, respectively. The sensitivity and specificity of Glasgow Coma Scale score 8 in predicting the mortality was 90% and 74%, respectively. The positive and the negative predictive values were 78% and 84%, respectively.
Functional Outcome at Discharge: Pediatric Overall Performance Category Score Of 38 survivors, 20 (52.6%) were categorized into good outcome and 18 (47.4%) were categorized having poor functional outcome at discharge. The area under the curve values predicting poor functional outcome at discharge (Pediatric Overall Performance Category score 3-6) for Glasgow Coma Scale was 0.732 (95% confidence interval: 0.564-0.862) and that for Full Outline of UnResponsiveness score was 0.746 (95% confidence interval: 0.579-0.873) (Figure 1). The difference between the areas under the curve for Glasgow Coma Scale and Full Outline of UnResponsiveness score was not statistically significant (0.013; 95% confidence interval: –0.06 to 0.09). The results indicate that both Glasgow Coma Scale and Full Outline of UnResponsiveness score are good predictors for poor functional outcome at discharge and Full Outline of UnResponsiveness score is not observed to be superior to Glasgow Coma Scale in predicting the poor functional outcome. The subunit analysis of Full Outline of UnResponsiveness score revealed that brainstem subscore had a lower area under
Total FOUR score FOUR score eye FOUR score motor FOUR score brainstem FOUR score respiration GCS total GCS eye GCS motor GCS verbal
Area under the curve (95% CI) for mortality
Area under the curve (95% CI) for poor outcome
0.940 (0.889-0.990) 0.857 (0.769-0.946) 0.896 (0.823-0.969) 0.716 (0.590-0.842) 0.865 (0.773-0.956) 0.916 (0.855-0.978) 0.830 (0.734-0.926) 0.896 (0.822-0.969) 0.786 (0.678-0.893)
0.746 (0.584-0.908) 0.706 (0.538-0.873) 0.606 (0.425-0.786) 0.611 (0.428-0.794) 0.638 (0.457-0.818) 0.732 (0.568-0.896) 0.612 (0.431-0.794) 0.789 (0.635-0.943) 0.660 (0.474-0.845)
Abbreviations: CI, confidence interval; FOUR, Full Outline of UnResponsiveness; GCS, Glasgow Coma Scale.
the curve value than eye, motor, and respiration components and total scores of Glasgow Coma Scale and the Full Outline of UnResponsiveness score had higher area under the curve values than subunit scores (Table 3). The odds ratio for mortality prediction with total Full Outline of UnResponsiveness score and total Glasgow Coma Scale was calculated by logistic regression analysis. After adjusting for age, duration of symptoms, need for ventilation and severity of illness (Pediatric Index of Mortality score), the odds ratio for total Full Outline of UnResponsiveness score was 0.53; that is for every 1-point increase in Full Outline of UnResponsiveness score, there is 47% reduction in odds of mortality. Similarly, the adjusted odds ratio for the Glasgow Coma Scale score was 0.48 implicating that for every 1-point increase in total Glasgow Coma Scale score, there is 52% reduction in odds of mortality. In the logistic regression model, Full Outline of UnResponsiveness score, Glasgow Coma Scale score, and Pediatric Index of Mortality were found to be independent predictors of mortality.
Discussion The results from the current study demonstrate the feasibility of use of the Full Outline of UnResponsiveness score in pediatric patients with nontraumatic impairment of consciousness and good predictive value for in-hospital mortality and functional outcome at discharge. Children more than 5 years were recruited as there was no experience of the Full Outline of UnResponsiveness score in children less than 5 years at the start of the study and the eye and motor components of the score require some patient cooperation. Cohen et al13 found the score feasible to apply and reliable in children as young as 2 years of age. Thus, this score can be applied in younger populations and can be tested in our setting in further studies. The results are consistent with other adult studies and a pediatric study. In the only other pediatric study13 in 60 children, 35 pediatric critical care nurse raters participated and it was demonstrated that
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for in-hospital mortality, the area under the curve for the Full Outline of UnResponsiveness was 0.81 and that for the Glasgow Coma Scale score was 0.77. As in the current study, the differences in area under the curve values were not statistically significant. In a pooled analysis comprising 381 adult patients,18 the area under the curve for the total Full Outline of UnResponsiveness score was 0.88, and for the Glasgow Coma Scale scores the area under the curve was 0.87. The Full Outline of UnResponsiveness score provided additional information with respect to survival in the most severe cases (Glasgow Coma Scale score of 3). In the current study, the area under the curve values were higher than those obtained in previously published validation studies.9-13 The adjusted odds ratio for both the scores (0.52 for Full Outline of UnResponsiveness score and 0.48 for Glasgow Coma Scale) were lower compared with previous studies, implicating higher positive predictive value for survival with increasing scores. As there was a single rater in the present study who applied the scores and periodic check of the scores applied by a senior pediatric neurologist, this might have resulted in higher area under the curve values for both the scores. Outside the Mayo Clinic, the Full Outline of UnResponsiveness score has been validated in other countries with Italian,20 Spanish,21 and French22 versions. Marcati and colleagues20 found the score to be reliable, valid, practical, and accurate as a prognostic indicator. The area under the curve value for mortality in their study was 0.935 for the Full Outline of UnResponsiveness and 0.953 for the Glasgow Coma Scale. Thus, the new scale consistently demonstrates high predictive value and good interrater agreement and is practical to use. Being a new score, there are few criticisms of the Full Outline of UnResponsiveness score. A few studies outside the Mayo Clinic have found inclusion of brainstem and respiration components in the Full Outline of UnResponsiveness score to be not sufficient enough for replacing the Glasgow Coma Scale in clinical practice. In a study comparing Glasgow Coma Scale and Full Outline of UnResponsiveness score in emergency setting, Eken et al23 enrolled 185 patients older than 17 years who presented with an altered level of consciousness after head trauma or with neurologic complaints. Area under the curve values in predicting hospital mortality for Glasgow Coma Scale and Full Outline of UnResponsiveness score were 0.735 and 0.788, respectively. The area under the curve value of brainstem and respiration component was 0.598 and 0.585, respectively. The authors concluded that Full Outline of UnResponsiveness Score was not superior to the Glasgow Coma Scale as the brainstem reflexes and respiratory pattern did not provide the expected benefit to using the eye and motor components. In another study, Fischer and colleagues24 observed that the interrater reliability for the Full Outline of UnResponsiveness score was at least as good as that of the Glasgow Coma Scale and they found the Full Outline of UnResponsiveness score to be superior to the Glasgow Coma Scale with regard to exact interrater agreement. They demonstrated that the interrater agreement was lowest for the ‘‘brainstem’’ component. Although the new Full Outline of UnResponsiveness score has many advantages over the Glasgow Coma Scale as stated
above, the difference between the areas under the curve for Glasgow Coma Scale and Full Outline of UnResponsiveness scores was not statistically significant as in most other studies. But this does not completely negate the benefits of the Full Outline of UnResponsiveness score. Rather, the present study forms the basis for feasibility of further longitudinal studies to compare Glasgow Coma Scale and Full Outline of UnResponsiveness scores in children for serial monitoring of patients and to examine if the above-mentioned advantages of the Full Outline of UnResponsiveness score aid in better monitoring and decision making in treatment of the patients. Moreover, patients with the lowest Glasgow Coma Scale score (3-5) had Full Outline of UnResponsiveness score values between 0 and 8, emphasizing that the latter provides more neurologic detail in severely affected patients and might be more useful than the Glasgow Coma Scale score in tracking the clinical status of patients. The lower area under the curve values of the brainstem component of the Full Outline of UnResponsiveness score in the present study (0.716) demonstrate that it does not provide the expected benefit to using eye and motor components of the score. Nevertheless, the brainstem component may prove to be useful in careful monitoring of the children. This is one of the first few studies evaluating the Full Outline of UnResponsiveness score in children with nontraumatic impairment of consciousness. At the time of initiation of the present study, there were no published studies in pediatric patients. Second, we had measures for proper training of the investigator by use of videos and periodic cross checking by the pediatric neurologist. Lastly, the outcomes used are objective and the functional outcome measure (Pediatric Overall Performance Category) was used at discharge, which has been validated for pediatric patients. The limitation of the study was that a single rater performed both scores and thus the interrater reliability could not be tested. Another limitation is that the sample size was calculated estimating the area under the curve for Glasgow Coma Scale score as 0.8; in the present study, we observed area under the curve as 0.916. So, the study was under-powered to detect the statistically significant advantage of Full Outline of UnResponsiveness score.
Conclusion Both Glasgow Coma Score and Full Outline of UnResponsiveness score are good predictors for in-hospital mortality and functional outcome at discharge in children with nontraumatic impairment of consciousness. No significant difference was observed between the ability of the 2 scores to predict the mortality and functional outcome at discharge. For assessing other properties of an ideal coma score, further studies need to be carried out to assess interrater agreement and predictive validity and accuracy of scores done by nursing staff and intensive care unit residents. Acknowledgments The work was performed at the All India Institute of Medical Sciences (AIIMS), New Delhi, India.
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Author Contributions All authors contributed to the content of the manuscript. GSK was the principal investigator and did the clinical evaluation and scoring of all the children, reviewed the literature, and prepared the manuscript. RL contributed to designing and conceptualizing the study, supervised the data collection, and helped in drafting the manuscript and data analysis. RMP performed the analysis and interpretation of the data. SG was overall in charge of the case; trained the investigator (GSK), supervised the data collection, did periodic reevaluation of the investigator, and approved the final version of the manuscript.
Declaration of Conflicting Interests The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The authors received no financial support for the research, authorship, and/or publication of this article.
Ethical Approval This study was approved by institutional ethics committee, All India Institute of Medical Sciences New Delhi, India (T-17/01.05.09). Written informed consent was obtained from the parents/guardians for all patients.
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