The focus of critical care has evolved from saving lives to preservation of function. Morbidity rates in pediatric critical care are approximately double mortality rates. Morbidity includes complications of disease and medical care. In pediatric critical care, functional status morbidity is an intermediate outcome in the progression toward death and is the result of the same factors associated with mortality, including physiologic profiles and case-mix factors. The Functional Status Scale developed by Collaborative Pediatric Critical Care Research Network is a validated, granular, age-independent measure of functional status that has proved valuable and practical even in large outcome studies.
Key points
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Morbidity is an important outcome that can be measured even for large studies. There are many measures of morbidity that can be selected based on the context of the study.
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In pediatric critical care, functional status is an “intermediate” outcome on the pathway to death that is significantly associated with physiologic instability (measured by the Pediatric Risk of Mortality [PRISM] score).
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Morbidity risk in pediatric critical care can be measured using physiologic profiles (PRISM) and other case-mix factors and used for quality assessment in a manner similar to death.
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New functional status morbidity rates are approximately double mortality rates.
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The Functional Status Scale (FSS) developed by the Collaborative Pediatric Critical Care Research Network is a granular method of measuring functional status and new functional status morbidity that is applicable to large-sample studies.
Introduction
The primary focus of critical care has evolved from saving lives by monitoring and maintaining physiologic status to placing greater emphasis on the prevention of secondary injuries and preservation of function. Current pediatric ICU (PICU) mortality rates approximate 2.5% to 5%, decreased from 8% to 18% during the early years of pediatric critical care, and it has been suggested that a portion of the reduced mortality rates has been an exchange for higher morbidity rates.
Pediatric critical care does not have a consensus concept of morbidity. Despite the low mortality rates and changing primary focus of pediatric critical care to include morbidity prevention, the primary outcome for many critical care studies and assessments remains mortality. Studies that formerly could be accomplished with mortality as a legitimate and meaningful outcome are now difficult or impossible due to sample size considerations. If mortality is the primary outcome for research, quality, or other studies, the sample size required may be very large and the time required to obtain these samples may be so long as to make the results less meaningful when the study is completed.
This article’s aims are
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To review the conceptual framework of morbidity most relevant to pediatric critical care
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Describe the uses of morbidity in research, quality, and other types of studies
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Describe measures of morbidity, especially those that measure functional status
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Review the foundational evidence that strongly supports the use of functional status morbidity as an equivalent or separate outcome to mortality
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Summarize the current pediatric critical care morbidity literature and the methods used to assess morbidity
Introduction
The primary focus of critical care has evolved from saving lives by monitoring and maintaining physiologic status to placing greater emphasis on the prevention of secondary injuries and preservation of function. Current pediatric ICU (PICU) mortality rates approximate 2.5% to 5%, decreased from 8% to 18% during the early years of pediatric critical care, and it has been suggested that a portion of the reduced mortality rates has been an exchange for higher morbidity rates.
Pediatric critical care does not have a consensus concept of morbidity. Despite the low mortality rates and changing primary focus of pediatric critical care to include morbidity prevention, the primary outcome for many critical care studies and assessments remains mortality. Studies that formerly could be accomplished with mortality as a legitimate and meaningful outcome are now difficult or impossible due to sample size considerations. If mortality is the primary outcome for research, quality, or other studies, the sample size required may be very large and the time required to obtain these samples may be so long as to make the results less meaningful when the study is completed.
This article’s aims are
- •
To review the conceptual framework of morbidity most relevant to pediatric critical care
- •
Describe the uses of morbidity in research, quality, and other types of studies
- •
Describe measures of morbidity, especially those that measure functional status
- •
Review the foundational evidence that strongly supports the use of functional status morbidity as an equivalent or separate outcome to mortality
- •
Summarize the current pediatric critical care morbidity literature and the methods used to assess morbidity
What is morbidity?
Morbidity is often difficult to define. Although mortality is simple (alive or dead), morbidity is usually conceptualized as an important deviation from baseline and/or a deviation from the expected result of care. In the context of critical care, morbidity is frequently thought of as the ramifications of both the disease process and the care provided in the ICU. It may encompass events during the inpatient stay, discharge status, or the long-term effects of the disease and the ensuing critical care interventions.
Morbidity during intensive care includes a diverse group of indicators, including the development of multisystem organ dysfunction, need for vasoactive medications, days on the ventilator, length of stay, hospital-acquired infections, and other medically focused outcomes. Morbidity, especially in the surgical literature, has increasingly been focused on inpatient complications or an unexpected hospital course associated with a procedure or its subsequent care, including length of stay, adverse events, and errors. An excellent example of using inpatient complications has been developed by using the congenital heart Society of Thoracic Surgeons Congenital Heart Surgery Database. The selected complications of specific interest and relevance to congenital heart surgery patients include renal failure requiring dialysis, neurologic deficits at discharge, atrioventricular block requiring a permanent pacemaker, mechanical circulatory support, phrenic nerve injury or paralyzed diaphragm, and unplanned operation. The result of combining these complications with postoperative length of stay has been standardized for specific operations, resulting in a morbidity index specifically relevant to these patients’ inpatient course, and suitable for use as a quality assessment method. Research by Kronman et al used more global measures of inpatient care such as cost. Contemporary trends, such as patient-centered care and family-centered care and cost, may be may also be converted to morbidity indicators, such as family-related and patient-related changes in stress, mental health, financial status, and family functioning.
Despite the traditional emphasis on inpatient metrics, there is growing recognition that the most important morbidities are decreases in functional status, which persist or develop after the hospital stay. These may be general, such as changes to activities of daily living, or organ-specific changes measured by functional tests, such as maximum oxygen consumption after cardiac surgery or pulmonary function tests after thoracic disease. Both types of morbidities are important. A recent review found that new functional impairment at the time of ICU discharge was reported from 10% to 36% of discharges depending on the methodology used. Evidence detailed in this article indicates that changes to functional status in critically ill children are tightly linked to physiologic dysfunction (severity of illness).
The relationship of physiologic dysfunction to morbidity
Morbidity often represents an intermediate outcome in a critically ill patient’s progression toward death and is likely the result of the same physiologic dysfunctions that are associated with mortality ( Fig. 1 ). Therefore, the conceptual foundation of intensive care, maintaining physiologic stability to prevent mortality, can be extended to morbidity, indicating that morbidity is a suitable and generalizable outcome measure for critical care quality assessments and research studies.
Although it has been well known for decades that physiologic dysfunction early in the PICU course is strongly associated with mortality risk, the association of physiologic dysfunction with morbidity has only recently been evaluated. The Collaborative Pediatric Critical Care Research Network (CPCCRN) of the Eunice Kennedy Shriver National Institute of Child Health and Human Development assessed the relationship of physiologic profiles measured within the first 4 hours of admission to the ICU to both mortality and the development of significant, new functional status morbidity at hospital discharge. This study is the Trichotomous Outcome Prediction in Critical Care (TOPICC) study. The measure of physiologic profiles is the Pediatric Risk of Mortality (PRISM) score and the measure of morbidity is the Functional Status Scale (FSS [discussed later]).
The CPCCRN study first identified a similar relationship between physiologic profiles and the development of new functional status morbidities as the relationship between physiologic profiles and mortality. As the physiologic instability increased, there was an increasing risk of both morbidity and mortality ( Fig. 2 A, B). Next, the TOPICC study determined the factors associated with the development of morbidity and mortality for critically ill children. Table 1 compares the univariate odds ratios of developing either morbidity or mortality given the descriptive or physiologic factors. In general, the risk factors for dying are also the risk factors for development of morbidity and when a variable is significant for one outcome, it is often significant for the other. Because the morbidity rate is twice as high as the mortality rate, most of the variables have higher odds ratios for morbidity than mortality. Importantly, physiologic profiles measured by the 4-hour PRISM score were significant for the risk of developing both morbidity and mortality, and they are even a more powerful predictor of morbidity than mortality.
| Variable | New Morbidity (%) | Death (%) | Odds Ratios: New Morbidity vs No New Morbidity (Odds Ratio [95% CI]) | Odds Ratios: Death vs No New Morbidity (Odds Ratio [95% CI]) |
|---|---|---|---|---|
| Age at PICU admission a | ||||
| 0 d to <7 d | 7.10 | 11.30 | 1.93 (1.12, 3.35) | 5.12 (3.09, 8.50) |
| 7 d to <14 d | 12.00 | 9.60 | 3.40 (1.88, 6.15) | 4.53 (2.31, 8.88) |
| Primary system of dysfunction b | ||||
| Respiratory | 4.40 | 2.20 | 0.88 (0.55, 1.39) | 0.24 (0.16, 0.37) |
| Cancer | 5.70 | 2.50 | 1.16 (0.60, 2.23) | 0.28 (0.12, 0.63) |
| Cardiovascular disease — congenital | 4.50 | 4.20 | 0.92 (0.56, 1.51) | 0.47 (0.31, 0.71) |
| Endocrine | 0 | 0.40 | <0.01 (<0.01, >999) | 0.04 (0.01, 0.30) |
| Gastrointestinal disorder | 5.70 | 3.40 | 1.18 (0.61, 2.31) | 0.39 (0.19, 0.81) |
| Musculoskeletal condition | 3.10 | 0.30 | 0.61 (0.29, 1.30) | 0.03 (0.00, 0.24) |
| Neurologic | 7.10 | 2.40 | 1.47 (0.93, 2.34) | 0.27 (0.17, 0.43) |
| Miscellaneous | 1.80 | 1.30 | 0.34 (0.15, 0.77) | 0.14 (0.06, 0.33) |
| Intervention category c | ||||
| Neurosurgery | 3.40 | 0.80 | 0.59 (0.36, 0.96) | 0.20 (0.07, 0.54) |
| Orthopedic | 2.60 | 0 | 0.45 (0.21, 0.97) | <0.01 (<0.01, >999) |
| Otolaryngology | 1.70 | 0 | 0.29 (0.14, 0.63) | <0.01 (<0.01, >999) |
| Miscellaneous | 1.60 | 1.20 | 0.27 (0.10, 0.74) | 0.31 (0.10, 0.98) |
| Acute (nonprimary) or chronic diagnosis of cancer d | ||||
| Yes | 5.90 | 7.40 | 1.37 (0.81, 2.30) | 2.95 (1.83, 4.76) |
| Trauma e | ||||
| Trauma | 11.90 | 3.50 | 3.14 (2.32, 4.24) | 1.40 (0.84, 2.32) |
| Admission source f | ||||
| Inpatient unit from same hospital | 6.60 | 5.60 | 2.15 (1.52, 3.02) | 3.79 (2.49, 5.76) |
| Direct admission from referring hospital | 7.20 | 4.90 | 2.33 (1.75, 3.09) | 3.31 (2.27, 4.83) |
| PICU admission status g | ||||
| Elective (scheduled) | 3.20 | 1.30 | 0.57 (0.44, 0.72) | 0.33 (0.23, 0.48) |
| Cardiac arrest h | ||||
| Yes | 15.40 | 38.50 | 6.91 (3.88, 12.3) | 33.3 (21.3, 52.0) |
| 4-Hour PRISM score i | ||||
| PRISM III (total) | 1.11 (1.09, 1.13) | 1.23 (1.21, 1.25) | ||
| PRISM III cardiovascular variables | 1.12 (1.06, 1.20) | 1.44 (1.37, 1.52) | ||
| PRISM III Metabolic Variables | 1.16 (1.12, 1.21) | 1.35 (1.30, 1.41) | ||
| PRISM III chemistry variables | 1.14 (1.07, 1.21) | 1.46 (1.38, 1.55) | ||
| PRISM III Hematological variables | 1.16 (1.10, 1.23) | 1.39 (1.32, 1.46) | ||
| PRISM III neurologic variables | 1.17 (1.13, 1.21) | 1.30 (1.27, 1.34) | ||
a Reference is age ≥144 months. Nonsignificant age categories were 14 days to less than 21 days, 21 days to less than 1 month, 1 month to less than 12 months, 12 months to less than 60 months, and 60 months to less than 144 months.
b Reference is acquired cardiovascular disease. Nonsignificant systems of dysfunction were hematological and renal.
c Intervention category. Reference is no intervention. Nonsignificant intervention categories included cardiovascular surgery, interventional catheterization, and general surgery.
d Cancer. Reference is no acute or chronic cancer.
e Trauma. Reference is no trauma.
f Admission source. Reference is operating room or postanesthesia care unit. Nonsignificant categories are admissions from the emergency department of the same hospital.
g Admission status. Reference is emergency.
h Cardiac arrest. Reference is no cardiac arrest.
Next, the TOPICC study developed a model to predict the 3 critical care outcomes—intact survival, survival with a functional status morbidity, and death at hospital discharge—simultaneously using multivariate trichotomous logistic regression (see Fig. 2 A, B). When the relationships of morbidity and mortality to physiologic profiles measured by the PRISM score are modeled separately, they were similar, with the risk of either mortality or morbidity increasing as physiologic instability increases. But, the relationship changes when both outcomes were considered simultaneously. As physiologic instability increased, both morbidity and mortality risk increased in parallel until mortality risk became dominant and the risk of morbidity decreased as those patients with a high mortality risk die. The association of morbidity risk to physiologic status, when mortality risk is factored in, is an inverted U shape. Morbidity risk first increased in parallel with mortality and then decreased.
This TOPICC study demonstrated that the same relationships underlying the association of mortality to physiologic status strongly influence the development of new, functional status morbidities at hospital discharge, as illustrated in Fig. 1 . The implications are important: just as providers have the ability to influence mortality risk by appropriately identifying and treating physiologic dysfunction, they have the ability to influence morbidity through the same mechanisms.
Importantly, this study was also able to develop and validate a predictor of the aforementioned 3 outcomes from critical care simultaneously ( Table 2 ). The relative risks for developing morbidity or mortality are reflected in the coefficients and odds ratios. Therefore, there is the potential to use both morbidity as well as mortality as meaningful ICU outcomes for quality assessments and researching new interventions because morbidity can be adjusted for using physiologic profiles and risk factors in the same way as mortality.
