Direct admission to the intensive care unit from the emergency department and mortality in critically ill hematology patients

One of the goals of emergency physicians is to detect, based on clinical characteristics and physiological derangements, patients without established organ dysfunction, but who are at high risk of early life-threatening complications. Such patients should be early admitted to the intensive care unit (ICU) or high dependency units as to benefit from close monitoring. Indeed, when these patients are admitted to classic wards, the level of monitoring may be inappropriate. Moreover, the workload that these high-risk patients impose to clinicians also hampers optimal management of remaining patients. The occurrence of complications in wards could lead to delays in patient optimal care and transfer to the ICU and, therefore, increase morbi-mortality [1]. This is even more likely for immunocompromised patients in whom the risk of deterioration is higher and less easily predictable [2].

Thus, we hypothesized that immunocompromised patients admitted to the ICU directly from the emergency department (ED), were admitted sooner and, may have better outcomes compared to similar patients, admitted to ICU from the wards.

The aim of this study was to assess the benefit of direct ICU admission from the ED compared to admission from wards, in patients with hematological malignancies requiring critical care.

This is a post hoc analysis derived from a prospective, multicenter cohort study of 1011 critically ill adult patients with hematologic malignancies admitted to 17 ICUs in Belgium and France from January 1, 2010 to May 1, 2011 [3]. Briefly, the study was carried out in university or university-affiliated centers in France and Belgium that belonged to a research network instituted in 2005. In all 17 centers, a senior intensivist and a senior hematologist are available around the clock and make ICU-admission decisions together. During the study period, consecutive patients having hematologic malignancies who were admitted to the participating ICUs for any reason were included. Exclusion criteria were complete cure of the malignancy for more than 5 years, ICU admission only to maximize safety of a procedure, and age younger than 18 years. For this post hoc analysis, patients with missing data on the outcome were also excluded. The study was approved by the appropriate ethics committees in France and Belgium. All patients or relatives were informed and consented to participate in the study.

In this post hoc analysis derived from a prospective, multicenter cohort study of 1011 critically ill adults patients with hematologic malignancies admitted to ICU, direct admission from the ED was associated with decreased in-hospital mortality in comparison with admission from the wards. This effect on mortality was confirmed in most of the sensitivity analyses except after matching on propensity score.

Benefit from appropriate and prompt ICU management is an established fact in myocardial infarction [9], ischemic stroke [10] or major trauma [11]. Along this line, early ICU admission of patients with some physiological derangement, before organ dysfunction actually develops, may be beneficial. Chalfin et al. showed that among 50,322 patients admitted to the ICU from the ED, those admitted with a ≥ 6 h delay had higher increased hospital length of stay (7 vs. 6 days, P < 0.001) and higher ICU and hospital mortality rates (10.7% vs. 8.4%, P < 0.01 and 17.4% vs. 12.9%, respectively, P < 0.001) [12]. This is also in agreement with the Renaud et al. study where patients with community-acquired pneumonia had different survival according to whether they were admitted to the ICU early, late or not admitted to the ICU (adjusted OR 2.63; 95% CI 1.42–4.90 for patients admitted early to the ICU) [13].

The use of ICU resources needs to be carefully discussed, however. Bed availability remains a major determinant of outcomes in settings where ICU resources are scarce [14]. Similarly, Cardoso et al. [15] found that delayed admission of patients requiring ICU management but for whom no bed was available had worse outcome than patients admitted immediately. They found that each waiting hour was independently associated with a 1% increase in risk of hospital death (hazard ratio = 1.010; 95% CI 1.002 to 1.018).

Patients with subtle physiological derangements that could foreshadow organ failure must be close monitored so as to prevent secondary deterioration. Hence, it may be hazardous to have these patients transferred to the wards. In a cohort of 841 septic patients transferred from the ED to the wards, Whittaker et al. [16] reported that 12.5% of patients were transferred to the ICU within 48 h and/or died within 28 days of admission. In this study, cancer was an independent risk factor of adverse outcome. Other studies have shown that septic patients admitted to ICU from wards had higher mortality rates [17, 18]. Last, in a study of cancer patients for whom an ICU admission was requested, 20% of the patients transferred to the wards because they were “too well” died [19]. This study suggests that ICU admission might have been inappropriately delayed and that delayed admission is associated with a high mortality rate.

Benefits from early ICU admission have also been reported in high-risk patients with malignancies and acute respiratory failure. In a prospective study on 219 patients with cancer admitted to the ICU for acute respiratory failure in France conducted by Mokart et al. [20], time between respiratory symptoms onset and ICU admission of at least 2 days was an independent predictor of day-28 mortality (OR: 2.65; 95% CI 1.29–5.44). In the present study, neither the delay between ICU request and ICU admission nor the number of calls before ICU admission was associated with in-hospital mortality by univariable analyses. These two variables were not included in the logistic regression model because of their colinearity with our variable of interest. Early detection of physiological derangement to allow prompt ICU admission is crucial and may be compromised in wards where surveillance is not optimal. Dedicated emergency teams have shown to be beneficial in case of soon intervention. After implementation of a medical emergency team in a comprehensive cancer center in Seoul [21], Song et al. [2] showed that in-hospital mortality rates increased significantly with increasing quartiles of time from physiological derangement to medical emergency team intervention in 199 critically ill cancer patients admitted to the ICU. Late intervention after 1.5 h after physiological derangement was significantly associated with in-hospital mortality in the multivariable analysis with adjustment for propensity score (OR: 3.91; 95% CI 1.93 to 7.94). These results remained true for long-term mortality in a study including 525 patients with cancer where early intervention was significantly associated with 1-year mortality after adjusting for potential confounders (hazard ratio: 0.456; 95% CI 0.348 to 0.597) [22].

Deciding the accurate timing for ICU admission may be challenging. ICU referral or admission decisions may be even more difficult in cancer patient when prognosis is uncertain [23]. Studies to incite early ICU management in high-risk patients are warranted. Besides survival benefits, organ dysfunction recovery and ability to receive optimal cancer care are critical endpoints of such interventions.

Our study has several limitations. First, this was a post hoc analysis of a cohort study dealing with the comparison of non-randomized groups. Obviously, because randomizing modalities of ICU admission may be complex, baseline characteristics of patients admitted from wards differ from those admitted directly from the ED. To handle these differences and limit selection bias, we performed a multivariable logistic regression to incorporate differences in baseline characteristics of these groups; however, it is possible that non-observed confounding factors exist such as hospital bed availability. Secondly, estimated benefit disappeared in the propensity score-matched sample, but this may be at least partially due to a lack of power given the limited sample size (402 vs. 1008) and on differences between matched and unmatched patients resulting in a selected population. However, variables that differed between both groups were already part of the multivariable logistic regression, except the type of underlying malignancy and the use of long-term corticosteroids. Thus, we reran a second multivariable analysis including these two variables and direct ICU admission remained associated with a better outcome. Third, we focus our research on patients with hematological malignancies admitted to the ICU and did not consider patients admitted to the wards who did not require or who were not referred to the ICU. Furthermore, patients admitted to the ICU from wards were not necessarily managed in the ED before. Fourth, we could not assess the time elapsed between the need for and the actual ICU admission. It could have been interesting to determine if patients admitted in wards had longer delays between first symptoms and ICU admission reflecting flaws in monitoring. Fifth, we did not consider the outcomes after hospital discharge. It is possible that a substantial part of these patients was transferred to palliative care unit lowering the benefit of survival at discharge.

In summary, in this post hoc study, patients with hematological malignancies admitted to the ICU were more likely to be alive at hospital discharge if they were directly admitted from the ED rather than from the wards. We are not yet to pretend that patients admitted to the ICU from wards who were previously managed in the ED should have been directly admitted from there. We, however, put forward that these high-risk patients need prompt specific management and close monitoring when they develop subtle physiological derangement to anticipate organ dysfunctions. This close monitoring may be inadequate in the wards and should be achieved by specialized teams in intensive care or high dependency units. Assessment of alarm signs and early predictors of poor outcome in cancer patients admitted to the ED is crucial so as to allow early referral to the ICU and avoid delays in treatment initiation and mis-orientation.