Intensive Care Med (5991) 17:I1-15
IntensiveCare Medicine 9 Springer-Verlag 1991
Outcome of oncology patients in the pediatric intensive care unit Y. S i v a n 1'2, P . H . S c h w a r t z 2, T. S c h o n f e l d 1, I . J . C o h e n 1 a n d C . J . L . N e w t h 2 1Pediatric Intensive Care Unit, Beilinson Medical Center, Petah Tikva, Tel Aviv University Sackler School of Medicine, Petah Tikva, Israel 2Division of Pediatric Intensive Care, Childrens Hospital Los Angeles, University of Southern California School of Medicine, Los Angeles, CA, USA Received: 9 July 1990; accepted: 27 September 1990
A b s t r a c t . We evaluated the o u t c o m e o f o n c o l o g y patients in the P e d i a t r i c Intensive C a r e U n i t ( P I C U ) f r o m a t o t a l o f 72 consecutive a d m i s s i o n s . Severity o f illness a n d q u a n t i t y o f care were m e a s u r e d b y the P h y s i o l o g i c Stability I n d e x (PSI) a n d t h e T h e r a p e u t i c I n t e r v e n t i o n S c o r i n g System (TISS), respectively. T h e overall m o r t a l i t y was 51 ~ a n d was especially high in p a t i e n t s a d m i t t e d for acute o r g a n system failure ( O S F ) - 66070. A c u t e respirat o r y failure was the m o s t f r e q u e n t O S F (73~ a n d the m o s t c o m m o n cause for P I C U a d m i s s i o n . A p o o r o u t come was associated with severe leucopenia ( < 1000 W B C / m m 3, 91070 m o r t a l i t y ) , acute renal failure (94~ m o r t a l i t y ) a n d central n e r v o u s system d e t e r i o r a t i o n (83070 m o r t a l i t y ) . W h e n t h e o u t c o m e was p r e d i c t e d using a q u a n t i t a t i v e a l g o r i t h m t h e o b s e r v e d m o r t a l i t y was sign i f i c a n t l y higher t h a n the p r e d i c t e d for all a d m i s s i o n s with a P S I higher t h a n 5. I m p r o v e d scoring systems are r e q u i r e d to enable c h a r a c t e r i z a t i o n o f p e d i a t r i c cancer p a t i e n t s a d m i t t e d to t h e P I C U . Key words: C h i l d r e n care
C a n c e r -- P r o g n o s i s - Intensive
T h e o u t c o m e o f a d u l t o n c o l o g y patients a d m i t t e d to t h e Intensive Care U n i t ( I C U ) has b e e n s h o w n to be p o o r despite increasing t h e r a p y [1 - 3 ] . Nevertheless, a d i s p r o p o r t i o n a t e a m o u n t o f resources were e m p l o y e d o n this p o o r o u t c o m e group. T h e nature, s p e c t r u m o f diseases, course a n d p r o g n o s i s o f c h i l d h o o d m a l i g n a n c i e s are different f r o m t h a t seen in a d u l t cancer. Thus, physicians c a r i n g for a c u t e l y ill p e d i a t r i c c a n c e r p a t i e n t s c a n n o t rely o n inf o r m a t i o n f r o m a n d experience with a d u l t s [4]. T h e r e has b e e n o n l y one s t u d y a d d r e s s i n g itself to this issue [5]. This was a retrospective h o s p i t a l c h a r t review o f p a t i e n t s i n c l u d i n g o n l y one m a j o r s u b g r o u p o f t h e p e d i a t r i c cancer p o p u l a t i o n : c h i l d r e n with h e m a t o l o g i c malignancy. T h e p u r p o s e o f t h e p r e s e n t s t u d y was to evaluate, p r o spectively, the o u t c o m e o f p e d i a t r i c p a t i e n t s with u n d e r -
lying m a l i g n a n c i e s a d m i t t e d to the P I C U , to delineate factors t h a t m a y affect the prognosis, a n d to assess the a p p l i c a b i l i t y o f p h y s i o l o g i c - b a s e d scoring m e t h o d s a n d p r o g n o s t i c p r e d i c t o r s in this u n i q u e g r o u p o f patients.
Patients and methods This prospective study is the result of collaboration between two multidisciplinary PICUs following the same study protocol: the Beilinson Medical Center, Petah-Tikva, Israel (Hospital A) and Childrens Hospital, Los Angeles, USA (Hospital B). Both medical centers are tertiary centers for pediatric intensive care and pediatric ontology. Patients were admitted at the request of the Pediatric Oncology service, on the understanding that once the acute illness had been overcome, further therapy would be provided for the basic disease from which a successful outcome was still possible. Patients with newly diagnosed brain tumors who were admitted to the PICU for short-term post-operative observation foUowing ventriculo-peritoneal shunt operation were not included in this study. These patients were not subjected to oncologic therapy at that time and did not have organ system failure. Patients with brain tumors who were admitted because of acute deterioration (sepsis, acute respiratory failure, etc.) or for post-operativecare and procedures while they were under oncologic follow-up or treatment, were included in the study. Data were collected daily from 72 consecutive admissions (47 in Hospital A and 25 in Hospital B) of pediatric cancer patients to the PICUs between 1986 and 1988. The information included: 1) demographic data, 2) past-medical history, 3) specific cause for PICU admission, 4) type of PICU admission criteria (acute organ system deterioration versus procedure and postoperative observation), 5) number and specific types of organ system failure (OSF), 6) length of PICU stay, 7) severity of illness, and 8) amount and type of treatment each patient received in the PICU. Organ system failure was defined using the criteria and principles of Wilkinson et al. [6]. These principles are based on clinical and laboratory measurements and the nature of supportive care. OSFs were diagnosed as extreme physiologic abnormalities, extremely abnormal laboratory values, or the need to use a hfe-sustaining therapy in order to ameliorate or eliminate these physiologic or laboratory abnormalities [6]. The variables were evaluated and correlated to outcome. Non-survival was defined as death in the PICU. Whenever a "do not resuscitate" order was applied, it was on the basis of the current disease status regardless of baseline oncologic disease. These patients died in the PICU ("non-survivors"). Two scoring systems applicable to pediatric intensive care were used. Between them they provide objective measures for determining severity
12
Y. Sivan et al.: Outcome of pediatric oncology in the PICU
Table 1. Mortality by underlying disease Underlying disease
Results
No.
Died (%)
15 10 4 1 2 3 4 4 43
5 8 a 0 2 2 2 3 24
Hematologic malignancies:
Acute lymphoblastic leukemia Acute myeloblastic leukemia Chronic myetocytic leukemia Congenital mixed ieukemia Acute nonlymphocytic leukemia Hodgkin lymphoma Non-Hodgkin lymphoma Histiocytosis Subtotal
(33) (80) (50) (100) (67) (50) (75) (56)
Solid tumors:
7 (78) 2 (40) 1 (50) 0 0 0 1 (loo) 0
Neuroblastoma Rhabdomyosarcoma Ewing sarcoma Osteogenic sarcoma Meningosarcoma Wilms tumor Astrocytoma Adrenal cortex carcinoma Hepatoblastoma Lung tumor Primitive neuroectodermal tumor Ependymoma Subtotal
9 5 2 I 1 4 1 1 2 1 1 1 29
0 1 (100) 0 13 (45)
Total
72
37 (51)
1 (50)
of illness, prediction of outcome, cost and manpower needs and enable comparison of patient care between PICUs [7-11]. 1. The Therapeutic Intervention Scoring System (TISS) was used daily to quantitate therapy and resources expended by assigning points from 1- 4 to various therapeutic interventions based on complexity and invasiveness [7, 9]. The TISS is applicable to children in PICU [7] and to acutely ill cancer patients [12]. The higher the score, the more care provided. 2. The Physiologic Stability Index (PSI) was used daily to assess objectively the severity of illness by quantitation of the degree of abnormality in 34 variables from 7 physiologic systems. This scoring system was designed specifically for the PICU population [8]. The higher the score, the more physiologically unstable the patient. Scores less than 9 generally correspond to low mortality risk, while scores greater than 24 correspond to high mortality risk [8, t3, 14]. The probability of death was calculated using the algorithm formulated by Pollack et al. [14]. This algorithm predicts the outcome of patients in the PICU according to a weighted sum of admission PSIs for the various organ systems and age. This mortality predictor has been assessed in 9 PICUs and was found to be highly reliable [14]. In addition, the relationship between the admission-day PSI and patient age and the probability of death was characterized by a multivariate logistic regression. We used the equation for logistic function derived by Pollack et al. [14] and compared the weightings assigned to each organ system with those of Pollack et al. Statistical evaluation of the data and comparison with published mortality prediction algorithms were done using SAS (SAS Institute, Cary, NC). Since most of the data collected were of the non-continuous interval type (i.e. yes or no, or points), non-parametric as welt as parametric analyses were used. Methods used included: Student t test, the Wilcoxon Rank Sums test for comparison of unpaired data, Wilcoxon Signed Ranks test for comparison of paired data, Fisher's ]Exact test, X2 test and Kruskal-Wallis test for comparison of multiple data. Whenever the distribution of a non-parametric variable was not a Gaussian distribution a transformation using square root was used and the Student t test was then applied. A p ~ 0.05 was taken to be significant.
T h e p a t i e n t p o p u l a t i o n , u n d e r l y i n g disease a n d g l o b a l o u t c o m e are shown in Table 1. T h e ratio o f a d m i s s i o n s for acute o r g a n system d e t e r i o r a t i o n to a d m i s s i o n s for procedures, t h e age range ( H o s p i t a l A : 5.5_+4.0 years, r a n g e 0 . 0 4 - 1 8 ; H o s p i t a l B: 8.8_+5.3 years, r a n g e 0.5 - 19), the l e n g t h o f P I C U stay for survivors a n d n o n survivors a n d the overall m o r t a l i t y rate (53% f o r H o s p i t a l A a n d 4 8 % for H o s p i t a l B) were c o m p a r a b l e (p > 0 . 0 5 ; S t u d e n t - t - t e s t a n d W i l c o x o n R a n k Sum). Similarly, the severity o f illness evaluated by a d m i s s i o n , m a x i m a l a n d average P S I scores a n d the a m o u n t o f t h e r a p y assessed by a d m i s s i o n , m a x i m a l a n d average T I S S scores were n o t different between t h e two h o s p i t a l s (p > 0 . 0 5 ; S t u d e n t t-test a n d W i l c o x o n R a n k Sum), so t h e results were c o m b i n e d (Table 2). T h e survival rate d i d n o t c o r r e l a t e with sex, age n o r d u r a t i o n o f stay in the P I C U ( W i l c o x o n R a n k Sum). T h e m o s t c o m m o n cause for P I C U a d m i s s i o n was a c u t e respir a t o r y failure - 27 p a t i e n t s (37%), with a m o r t a l i t y rate o f 74070. A l l o f t h e m required i n t u b a t i o n a n d v e n t i l a t o r y s u p p o r t . A c u t e p a r e n c h y m a l lung disease o c c u r r e d in 2 3 / 2 7 including: p n e u m o n i a , a d u l t r e s p i r a t o r y distress s y n d r o m e - n o n c a r d i o g e n i c p u l m o n a r y e d e m a a n d pulm o n a r y bleeding. F o u r p a t i e n t s h a d acute o b s t r u c t i v e airway disease: u p p e r airway o b s t r u c t i o n , vocal cord p a r a l y sis a n d right m a i n b r o n c h u s o b s t r u c t i o n . O u t o f these 4 p a t i e n t s 3 died. C a r d i o v a s c u l a r failure was the m a i n cause o f P I C U a d m i s s i o n in 17 cases (24%) w i t h a m o r tality o f 47%. Eleven (15%) p a t i e n t s were a d m i t t e d with t h e p r e d o m i n a n t p r o b t e m o f c e n t r a l n e r v o u s system (CNS) d e t e r i o r a t i o n ; this g r o u p h a d t h e highest m o r t a l i t y rate - 90%. T h e overall m o r t a l i t y was 51%, b u t o f 16 (22%) patients a d m i t t e d for m e d i c a l or surgical p r o c e dures including post-operative care, none died (p
IntensiveCare Medicine 9 Springer-Verlag 1991
Outcome of oncology patients in the pediatric intensive care unit Y. S i v a n 1'2, P . H . S c h w a r t z 2, T. S c h o n f e l d 1, I . J . C o h e n 1 a n d C . J . L . N e w t h 2 1Pediatric Intensive Care Unit, Beilinson Medical Center, Petah Tikva, Tel Aviv University Sackler School of Medicine, Petah Tikva, Israel 2Division of Pediatric Intensive Care, Childrens Hospital Los Angeles, University of Southern California School of Medicine, Los Angeles, CA, USA Received: 9 July 1990; accepted: 27 September 1990
A b s t r a c t . We evaluated the o u t c o m e o f o n c o l o g y patients in the P e d i a t r i c Intensive C a r e U n i t ( P I C U ) f r o m a t o t a l o f 72 consecutive a d m i s s i o n s . Severity o f illness a n d q u a n t i t y o f care were m e a s u r e d b y the P h y s i o l o g i c Stability I n d e x (PSI) a n d t h e T h e r a p e u t i c I n t e r v e n t i o n S c o r i n g System (TISS), respectively. T h e overall m o r t a l i t y was 51 ~ a n d was especially high in p a t i e n t s a d m i t t e d for acute o r g a n system failure ( O S F ) - 66070. A c u t e respirat o r y failure was the m o s t f r e q u e n t O S F (73~ a n d the m o s t c o m m o n cause for P I C U a d m i s s i o n . A p o o r o u t come was associated with severe leucopenia ( < 1000 W B C / m m 3, 91070 m o r t a l i t y ) , acute renal failure (94~ m o r t a l i t y ) a n d central n e r v o u s system d e t e r i o r a t i o n (83070 m o r t a l i t y ) . W h e n t h e o u t c o m e was p r e d i c t e d using a q u a n t i t a t i v e a l g o r i t h m t h e o b s e r v e d m o r t a l i t y was sign i f i c a n t l y higher t h a n the p r e d i c t e d for all a d m i s s i o n s with a P S I higher t h a n 5. I m p r o v e d scoring systems are r e q u i r e d to enable c h a r a c t e r i z a t i o n o f p e d i a t r i c cancer p a t i e n t s a d m i t t e d to t h e P I C U . Key words: C h i l d r e n care
C a n c e r -- P r o g n o s i s - Intensive
T h e o u t c o m e o f a d u l t o n c o l o g y patients a d m i t t e d to t h e Intensive Care U n i t ( I C U ) has b e e n s h o w n to be p o o r despite increasing t h e r a p y [1 - 3 ] . Nevertheless, a d i s p r o p o r t i o n a t e a m o u n t o f resources were e m p l o y e d o n this p o o r o u t c o m e group. T h e nature, s p e c t r u m o f diseases, course a n d p r o g n o s i s o f c h i l d h o o d m a l i g n a n c i e s are different f r o m t h a t seen in a d u l t cancer. Thus, physicians c a r i n g for a c u t e l y ill p e d i a t r i c c a n c e r p a t i e n t s c a n n o t rely o n inf o r m a t i o n f r o m a n d experience with a d u l t s [4]. T h e r e has b e e n o n l y one s t u d y a d d r e s s i n g itself to this issue [5]. This was a retrospective h o s p i t a l c h a r t review o f p a t i e n t s i n c l u d i n g o n l y one m a j o r s u b g r o u p o f t h e p e d i a t r i c cancer p o p u l a t i o n : c h i l d r e n with h e m a t o l o g i c malignancy. T h e p u r p o s e o f t h e p r e s e n t s t u d y was to evaluate, p r o spectively, the o u t c o m e o f p e d i a t r i c p a t i e n t s with u n d e r -
lying m a l i g n a n c i e s a d m i t t e d to the P I C U , to delineate factors t h a t m a y affect the prognosis, a n d to assess the a p p l i c a b i l i t y o f p h y s i o l o g i c - b a s e d scoring m e t h o d s a n d p r o g n o s t i c p r e d i c t o r s in this u n i q u e g r o u p o f patients.
Patients and methods This prospective study is the result of collaboration between two multidisciplinary PICUs following the same study protocol: the Beilinson Medical Center, Petah-Tikva, Israel (Hospital A) and Childrens Hospital, Los Angeles, USA (Hospital B). Both medical centers are tertiary centers for pediatric intensive care and pediatric ontology. Patients were admitted at the request of the Pediatric Oncology service, on the understanding that once the acute illness had been overcome, further therapy would be provided for the basic disease from which a successful outcome was still possible. Patients with newly diagnosed brain tumors who were admitted to the PICU for short-term post-operative observation foUowing ventriculo-peritoneal shunt operation were not included in this study. These patients were not subjected to oncologic therapy at that time and did not have organ system failure. Patients with brain tumors who were admitted because of acute deterioration (sepsis, acute respiratory failure, etc.) or for post-operativecare and procedures while they were under oncologic follow-up or treatment, were included in the study. Data were collected daily from 72 consecutive admissions (47 in Hospital A and 25 in Hospital B) of pediatric cancer patients to the PICUs between 1986 and 1988. The information included: 1) demographic data, 2) past-medical history, 3) specific cause for PICU admission, 4) type of PICU admission criteria (acute organ system deterioration versus procedure and postoperative observation), 5) number and specific types of organ system failure (OSF), 6) length of PICU stay, 7) severity of illness, and 8) amount and type of treatment each patient received in the PICU. Organ system failure was defined using the criteria and principles of Wilkinson et al. [6]. These principles are based on clinical and laboratory measurements and the nature of supportive care. OSFs were diagnosed as extreme physiologic abnormalities, extremely abnormal laboratory values, or the need to use a hfe-sustaining therapy in order to ameliorate or eliminate these physiologic or laboratory abnormalities [6]. The variables were evaluated and correlated to outcome. Non-survival was defined as death in the PICU. Whenever a "do not resuscitate" order was applied, it was on the basis of the current disease status regardless of baseline oncologic disease. These patients died in the PICU ("non-survivors"). Two scoring systems applicable to pediatric intensive care were used. Between them they provide objective measures for determining severity
12
Y. Sivan et al.: Outcome of pediatric oncology in the PICU
Table 1. Mortality by underlying disease Underlying disease
Results
No.
Died (%)
15 10 4 1 2 3 4 4 43
5 8 a 0 2 2 2 3 24
Hematologic malignancies:
Acute lymphoblastic leukemia Acute myeloblastic leukemia Chronic myetocytic leukemia Congenital mixed ieukemia Acute nonlymphocytic leukemia Hodgkin lymphoma Non-Hodgkin lymphoma Histiocytosis Subtotal
(33) (80) (50) (100) (67) (50) (75) (56)
Solid tumors:
7 (78) 2 (40) 1 (50) 0 0 0 1 (loo) 0
Neuroblastoma Rhabdomyosarcoma Ewing sarcoma Osteogenic sarcoma Meningosarcoma Wilms tumor Astrocytoma Adrenal cortex carcinoma Hepatoblastoma Lung tumor Primitive neuroectodermal tumor Ependymoma Subtotal
9 5 2 I 1 4 1 1 2 1 1 1 29
0 1 (100) 0 13 (45)
Total
72
37 (51)
1 (50)
of illness, prediction of outcome, cost and manpower needs and enable comparison of patient care between PICUs [7-11]. 1. The Therapeutic Intervention Scoring System (TISS) was used daily to quantitate therapy and resources expended by assigning points from 1- 4 to various therapeutic interventions based on complexity and invasiveness [7, 9]. The TISS is applicable to children in PICU [7] and to acutely ill cancer patients [12]. The higher the score, the more care provided. 2. The Physiologic Stability Index (PSI) was used daily to assess objectively the severity of illness by quantitation of the degree of abnormality in 34 variables from 7 physiologic systems. This scoring system was designed specifically for the PICU population [8]. The higher the score, the more physiologically unstable the patient. Scores less than 9 generally correspond to low mortality risk, while scores greater than 24 correspond to high mortality risk [8, t3, 14]. The probability of death was calculated using the algorithm formulated by Pollack et al. [14]. This algorithm predicts the outcome of patients in the PICU according to a weighted sum of admission PSIs for the various organ systems and age. This mortality predictor has been assessed in 9 PICUs and was found to be highly reliable [14]. In addition, the relationship between the admission-day PSI and patient age and the probability of death was characterized by a multivariate logistic regression. We used the equation for logistic function derived by Pollack et al. [14] and compared the weightings assigned to each organ system with those of Pollack et al. Statistical evaluation of the data and comparison with published mortality prediction algorithms were done using SAS (SAS Institute, Cary, NC). Since most of the data collected were of the non-continuous interval type (i.e. yes or no, or points), non-parametric as welt as parametric analyses were used. Methods used included: Student t test, the Wilcoxon Rank Sums test for comparison of unpaired data, Wilcoxon Signed Ranks test for comparison of paired data, Fisher's ]Exact test, X2 test and Kruskal-Wallis test for comparison of multiple data. Whenever the distribution of a non-parametric variable was not a Gaussian distribution a transformation using square root was used and the Student t test was then applied. A p ~ 0.05 was taken to be significant.
T h e p a t i e n t p o p u l a t i o n , u n d e r l y i n g disease a n d g l o b a l o u t c o m e are shown in Table 1. T h e ratio o f a d m i s s i o n s for acute o r g a n system d e t e r i o r a t i o n to a d m i s s i o n s for procedures, t h e age range ( H o s p i t a l A : 5.5_+4.0 years, r a n g e 0 . 0 4 - 1 8 ; H o s p i t a l B: 8.8_+5.3 years, r a n g e 0.5 - 19), the l e n g t h o f P I C U stay for survivors a n d n o n survivors a n d the overall m o r t a l i t y rate (53% f o r H o s p i t a l A a n d 4 8 % for H o s p i t a l B) were c o m p a r a b l e (p > 0 . 0 5 ; S t u d e n t - t - t e s t a n d W i l c o x o n R a n k Sum). Similarly, the severity o f illness evaluated by a d m i s s i o n , m a x i m a l a n d average P S I scores a n d the a m o u n t o f t h e r a p y assessed by a d m i s s i o n , m a x i m a l a n d average T I S S scores were n o t different between t h e two h o s p i t a l s (p > 0 . 0 5 ; S t u d e n t t-test a n d W i l c o x o n R a n k Sum), so t h e results were c o m b i n e d (Table 2). T h e survival rate d i d n o t c o r r e l a t e with sex, age n o r d u r a t i o n o f stay in the P I C U ( W i l c o x o n R a n k Sum). T h e m o s t c o m m o n cause for P I C U a d m i s s i o n was a c u t e respir a t o r y failure - 27 p a t i e n t s (37%), with a m o r t a l i t y rate o f 74070. A l l o f t h e m required i n t u b a t i o n a n d v e n t i l a t o r y s u p p o r t . A c u t e p a r e n c h y m a l lung disease o c c u r r e d in 2 3 / 2 7 including: p n e u m o n i a , a d u l t r e s p i r a t o r y distress s y n d r o m e - n o n c a r d i o g e n i c p u l m o n a r y e d e m a a n d pulm o n a r y bleeding. F o u r p a t i e n t s h a d acute o b s t r u c t i v e airway disease: u p p e r airway o b s t r u c t i o n , vocal cord p a r a l y sis a n d right m a i n b r o n c h u s o b s t r u c t i o n . O u t o f these 4 p a t i e n t s 3 died. C a r d i o v a s c u l a r failure was the m a i n cause o f P I C U a d m i s s i o n in 17 cases (24%) w i t h a m o r tality o f 47%. Eleven (15%) p a t i e n t s were a d m i t t e d with t h e p r e d o m i n a n t p r o b t e m o f c e n t r a l n e r v o u s system (CNS) d e t e r i o r a t i o n ; this g r o u p h a d t h e highest m o r t a l i t y rate - 90%. T h e overall m o r t a l i t y was 51%, b u t o f 16 (22%) patients a d m i t t e d for m e d i c a l or surgical p r o c e dures including post-operative care, none died (p
