MODEL CPTS THESIS PROPOSAL
Off-Hours Admission and Mortality in the Pediatric Intensive Care Unit
Thesis Proposal – Wake Forest Clinical and Population Translational Sciences Master’s Program
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Background: Among more than 40,000 deaths annually in children 18 years and younger in the United States, greater than 50% occur in the hospital setting [1, 2]{Slonim, 2010 #8;, 2011 #67}. An estimated 80-90% of pediatric in-hospital deaths occur in an intensive care unit (ICU), with approximately 56% of pediatric in-hospital deaths occurring in the pediatric ICU and >80% of pediatric in-hospital deaths in non-neonates occurring in the pediatric ICU [3, 4]. Overall mortality in the pediatric ICU is estimated at approximately 3% [5], though certain patient and system factors may significantly increase hospitalized children’s risk of death. Average age of patients in the pediatric ICU is approximately 6.8 years [5]. However, >50% of pediatric in-hospital deaths are in patients under 1 year of age [1, 4], with those who died in the pediatric ICU being a median of 5 months old in one study [3], demonstrating the significant burden of years of life lost.
Admission of severely ill or decompensating patients to an ICU can occur at any time, however organizational and other factors may vary by time of day and day of the week. Therefore, admission during off-hours as compared with regular daytime hours has been hypothesized to confer an increased risk of mortality in the ICU setting. Although definitions are heterogeneous, off-hours are often defined as nights (often 5pm or 7pm until around 7am), weekends, and holidays. At least 15 studies have evaluated this potential association in adult ICUs, with conflicting results. A recent meta-analysis of 10 such studies evaluating over 100 adult ICUs and more than 130,000 admissions found that nighttime admission was not associated with an increased mortality when compared with daytime, with an odds ratio (OR) of 1.0 [95% CI 0.87-1.17]. However, admission during the weekend was associated with increased mortality when compared with weekdays in this meta-analysis, with an OR of 1.08 [95% CI 1.04-1.13] [6]. In-hospital mortality was the outcome measure in 8 of the 10 studies included in this analysis, with the remainder using ICU mortality. The largest study not included in this meta-analysis, published subsequently, evaluated over 149,000 patients (>95% age 20 years or older) in a national registry of more than 70 ICUs in the Netherlands. Mortality was higher during off-hours in this study, with a relative risk for in-hospital mortality of 1.06 (95% CI 1.03-1.09) during off-hours overall and a relative risk of mortality of 1.1 (95% CI 1.07-1.14) on weekends specifically [7]. Of note, mortality rates during both daytime and off-hours in these adult studies were 10-40%, substantially higher than those found in the pediatric setting.
The relationship between off-hours admissions and mortality in the pediatric ICU has been directly evaluated in 6 studies in the peer-reviewed literature, with 4 of these being single-center studies, also with conflicting results. The largest study to date of off-hours admissions to the pediatric ICU analyzed 20,547 admissions to 15 pediatric ICUs from 1995-2001 and evaluated only emergency admissions. In this study, risk of mortality within 48 hours was higher (OR 1.28) for admissions during the nighttime compared with daytime, however the 95% confidence interval included unity (95% CI 1.00-1.62) [8]. The only other multi-center study in the pediatric ICU setting examined 3,212 admissions to two pediatric ICUs in the Netherlands from 2003-2007 and found no difference in mortality risk for off-hours vs. daytime admissions after adjustment for severity of illness (OR 0.95 [95%CI 0.71-1.27]) [9]. Of the four single-center studies in the pediatric ICU setting, two found no difference in mortality during off-hours when adjustment was made for severity of illness [10, 11], while one study in a pediatric cardiac ICU found higher mortality between the specific hours of 8pm and 2am (OR for mortality compared with other times of admission 1.64, 95%CI 1.08-2.50), and the largest single-center study of 4,456 non-elective admission to a pediatric ICU in Australia found lower risk-adjusted mortality during off-hours as compared with weekdays (OR 0.71, 95%CI 0.52-0.98) [12]. In summary, results of investigation into a potential relationship between off-hours admission to the pediatric ICU and increased mortality have been inconsistent, perhaps related to the heterogeneity of patient populations, staffing patterns, and the small size of most studies. However, findings in larger studies in adults as well as the largest study to date in children have indicated some increased risk of mortality during off-hours, indicating that further investigation is warranted. No study has evaluated a large national sample of pediatric ICU admissions comparable to larger adult studies, and all studies to date have included only admissions prior to 2007.
The possible pathway for increased risk of mortality for patients admitted during off-hours in the pediatric ICU includes patient (admission) characteristics, organizational factors, and human factors. A proposed conceptual model is displayed in Figure 1. Emergent, non-elective admissions to the pediatric ICU may occur at any time, but after-hours admissions are relatively more likely to be emergencies since scheduled admissions such as those after planned operative procedures typically occur on weekdays [8, 9, 11-13]. In a study at a large U.S. tertiary care pediatric ICU, emergency admissions accounted for 27% of weekday vs. 80% of weekend admissions [11], with crude mortality also being significantly higher on weekends (weekday: 2.2% mortality; weekend: 5.0% mortality, p<0.001). In another study at a large pediatric cardiac ICU in Europe, evening admissions were more likely to be emergencies (daytime 29% emergencies; nighttime 65% emergencies) and had higher observed mortality (daytime: 3.8% mortality; nighttime: 10.7% mortality, p<0.001) [13].
Figure 1: Conceptual model for off-hours admission leading to increased mortality in the pediatric ICU
Several of the diagnoses most highly associated with death in children, including cardiac arrest (odds ratio (OR) for death of 232.3 compared with other hospitalized children), pulmonary edema and respiratory failure (9.2), multi-trauma without operative intervention (OR 7.8), and septicemia and disseminated infections (OR 7.1) [1] have evidence-based interventions associated with them that must be performed within a critical period of seconds to minutes to be most effective. One example of an emergent intervention in the ICU setting is the recommendation that high-quality chest compressions are initiated after no more than 10 seconds of pulse check in cardiac arrest [14]. One large study of >58,000 cases of in-hospital cardiac arrest in adults found that survival to discharge was higher when the cardiac arrest occurred during the daytime vs. night (OR 1.18, 95%CI 1.12-1.23), and also higher when the cardiac arrest occurred on a weekday vs. weekend day (OR 1.15, 95%CI 1.09-1.22) [15]. Another study of 102 cardiac arrests in a pediatric cardiac ICU demonstrated a significantly higher odds of successful resuscitation on weekdays vs. weekends (OR 3.8, 95%CI 1.2-11.5), with weekend nights having the highest rate of unsuccessful resuscitation [16]. Primary admission diagnosis, as well as presence of cardiac massage prior to pediatric ICU admission and several other relevant patient admission characteristics are included data elements in the Virtual Pediatric Intensive Care Systems, limited liability corporation (VPS, LLC) database, and such characteristics as well as severity of illness for weekday and off-hours admissions will be characterized.
Severity of illness scoring systems are often used to quantify and attempt to control for risk of mortality based on certain patient or admission factors. In pediatric intensive care, the Pediatric Index of Mortality 2 (PIM2) score and the Pediatric Risk of Mortality III (PRISM III) are the two most commonly used scoring systems. A variant of one or both of these scores was used in each of the studies previously mentioned investigating the association between off-hours admission and mortality in pediatric intensive care, in an effort to control for severity of illness in multivariate analysis and focus on organizational or human factors that could be modified. The PIM2 score incorporates 10 variables collected at the time of admission to the ICU to estimate mortality risk, including 4 physiologic variables and 6 admission factors, including whether the admission is emergent and whether the reason for admission fits within a low or high risk category (see Appendix for basic components of PIM2 and PRISM III scores). The PIM2 score was validated in 20,787 children from 14 ICUs in Australia, New Zealand, and the United Kingdom and was found to discriminate between death and survival well, with a receiver operator characteristic of 0.90 (95% CI 0.89-0.91) [17]. The PRISM III score uses 17 physiologic variables collected in the first 12-24 hours of a patient’s ICU stay [18], with the most abnormal values for vital sign or laboratory parameters used when multiple values are collected in this time period. The PRISM III score was validated in 11,165 admissions from 32 PICUs with a receiver operator characteristic of 0.94 (95%CI 0.92-0.96), also indicating very good discrimination. For the purposes of this study, PIM2 score will be included in the primary multivariate analysis as this is a required data element in the VPS database, however a second analysis will be performed using PRISM III to determine whether a significantly different result is found for the admissions including PRISM III data.
Staffing during off-hours may vary for physicians, nurses, as well as other staff. Several studies have investigated the effect of attending ICU physician staffing in both adult and pediatric intensive care, with studies generally showing benefit from having ready access to intensivist care, but unclear benefit from 24/7 in-house attending coverage. The Leapfrog group, a major United States patient safety organization, has issued recommendations for adult and pediatric ICU physician staffing, stating that an attending intensivist should be present during daytime hours and provide clinical care exclusively in the ICU during this time. During off-hours, the intensivist should return pages 95% of the time within 5 minutes and have a designee (such as a physician or nurse practitioner) on-site and able to reach a patient within 5 minutes [19]. A systematic review of the adult ICU literature found that high-intensity staffing with mandatory intensivist involvement (although not necessarily always on-site) conferred a lower risk of hospital and ICU mortality (relative risk for hospital mortality 0.71, 95%CI 0.62-0.82; for ICU mortality 0.61, 95% CI 0.50-0.75) [20]. A more recent retrospective cohort study of a large database of adult ICU admissions including over 65,000 patients admitted to 49 ICUs found that nighttime on-site intensivist staffing was associated with a decreased risk of mortality in a low-intensity staffing model without mandatory intensivist coverage during the day (odds ratio for death 0.61, 95%CI 0.39-0.97), however there was no difference in mortality with nighttime intensivist staffing when a high-intensity daytime model was present (OR 1.08, 95% CI 0.63-1.84) [21]. Furthermore, resident staffing at night in the ICU setting is likely decreased compared with daytime, especially given work hour restrictions [22], which would reduce overall on-site physician number and may have additional effect on patient outcome.
In the pediatric ICU, 24/7 intensivist coverage appears to have become much more common over time, however any benefit on outcomes is unclear. A survey published in 2004 reported that 94% of United States pediatric ICUs had a pediatric intensivist on staff, with 17% being in-house overnight [23]. A more recent report indicated that 45% of 29 pediatric ICUs surveyed had 24/7 intensivist coverage [24], while a query of the VPS database from 2006-2008 found that 42% of the 67 pediatric ICUs had 24/7 intensivist presence. In the latter study, pediatric ICUs with 24/7 intensivist coverage did not have any overall difference in mortality, length of ICU stay, or duration of mechanical ventilation [25].
Several other studies have examined the impact of increased off-hours physician staffing in the pediatric ICU stetting using pre-post interventional design. A study at 2 pediatric ICUs in the United States found increased odds of survival associated with introducing a hospitalist in-house overnight rather than only resident physicians (OR for survival 2.8, 95%CI not given) [26]. A study of a single pediatric ICU in Malaysia found a decreased standardized mortality ratio from 1.57 (95%CI 1.25-1.95) to 0.56 (95% CI 0.47-0.67) associated with 24-hour intensivist coverage rather than off-site general pediatricians providing coverage [27]. More recently, a report of 18,702 patient admissions to a large tertiary care center indicated that duration of mechanical ventilation was reduced by 35% (95%CI 25-44) and ICU length of stay was shorter (mean 4.7 vs. 4.3 days) after 24/7 attending intensivist coverage was instituted, with no significant effect on mortality [28]. While interesting, each of these studies may have been biased by maturation effect since the increased staffing model was always evaluated at a later time point, when other factors in the care of critically ill children in general or at that institution may have changed.
Staffing models of nurses and other staff may also influence outcome of pediatric ICU patients during off-hours. In one study of greater than 27,000 ICU patients from over 200 hospitals in Korea, every additional patient per nurse was associated with a 9% increased odds of death (OR 1.09, 95%CI 1.04-1.14). In this same study, lack of a board-certified attending presence in the ICU for 4 or more hours per day was also significantly associated with death (OR 1.56, 95%CI 1.20-2.01) [29]. In a meta-analysis of studies of nurse staffing in ICUs, increased nurse staffing was associated with decreased odds of death (OR 0.91, 95%CI 0.86-0.96) as well as decreased risk of hospital-acquired pneumonia, unplanned extubation, respiratory failure, and cardiac arrest [30]. Two studies have found an increased risk of unplanned extubation with higher patient/nurse ratios in the pediatric ICU setting specifically [31, 32]. While no study has characterized whether nursing staffing patterns are consistently different during off-hours in the pediatric ICU, it appears that if present, such differences could influence outcome. Another staffing group which may be less likely to be fully available during off-hours are pediatric-trained pharmacists. One study at a large children’s hospital found that medication errors were significantly more likely to occur during off-hours (1.17 errors per 1000 doses during daytime vs. 2.12 errors per 1000 doses during nighttime, p=0.005) [33]. Another study reported a drop in serious medication errors in the pediatric ICU from 29 to 6 per 1000 patient days with introduction of a full-time unit-based clinical pharmacist [34]. While availability of nursing, pediatric pharmacists, as well as other specialized support (such as respiratory therapy, laboratory, radiology, or others) during off-hours in the pediatric ICU may be variable and incompletely defined, limited data suggest that relevant outcomes may be affected by decreased staffing of these groups as well and could contribute to any overall effect of off-hours admission on mortality.