Analysis of emergency head computed tomography in critically ill oncological patients

Acute neurological dysfunction is common in patients admitted to the Intensive Care Unit (ICU) with a wide spectrum of neurological findings including depressed consciousness, delirium, seizures and focal neurological signs.1 Underlying etiologies include, but are not limited to, stroke (due to hemodynamic instability and coagulation abnormalities), use of sedative drugs, systemic inflammatory response and metabolic and endocrine disturbances.2

Emergency head computed tomography (EHCT) is often performed in critically ill patients to investigate neurologic signs and symptoms, such as focal neurologic deficits and seizure activity. The utility of imaging for patients who develop nonspecific altered mental status (AMS) is unclear.3 AMS is a broad term, and can imply either change in consciousness (supratentorial function) or in arousal (executed by the brainstem). Underlying etiologies include both systemic and central nervous system processes, the latter encompassing both organic and functional causes. The complex differential diagnosis can make AMS a potentially vexing clinical problem.4

Obviously, EHCT can provide important information for patient management, but in critically ill patients there are risks associated with transport and examination.3 In addition, the financial expenses of possible unnecessary testing should also be taken into consideration.5 Therefore, an EHCT request in an ICU patient should be carefully assessed, in order to decide if the potential benefits outweigh the risks.

Studies on head CTs use and appropriateness in critically ill medical and surgical patients were previously conducted, to assess the usefulness of clinical variables in selecting patients to be scanned2,6,7 or to provide estimates of the frequency of acute changes on head CTs and therefore, their diagnostic yield.3,8, 9, 10

Critically ill oncological patients have an increased risk of developing acute neurological dysfunction due to several reasons. Sepsis is the most frequent cause of ICU admission in oncological patients; therefore, septic encephalopathy is common. Multiple organ dysfunction increases the risk for metabolic neurological dysfunction related to renal, hepatic or electrolytic disturbances. Thrombocytopenia and coagulation abnormalities predispose to intracranial bleeding. Central nervous system metastasis/infiltration by malignant cells may be present. The differential diagnosis of putative processes is challenging in these complex circumstances.

Therefore, the primary aim of this study was to evaluate EHCT diagnostic yield in a cohort of oncological patients treated in a mixed, non-neurosurgical ICU. Furthermore, we evaluated the distribution of positive EHCT according to the type of malignancy (hematological or solid tumour) and the relationship between positive EHCT and clinical indications. Finally, we evaluated the patients’ outcomes related to their EHCT results.

Our study showed a high rate of newly diagnosed intracranial processes by EHCT in a cohort of non-neurosurgical oncological patients admitted to ICU for non-neurological reasons. Exclusion of neurosurgical patients is worth mentioning, because this class of patients demands more scans for diagnosis and follow-up, usually with a higher probability of positive findings.

The main indications for EHCTs in our study were FND/seizure. Analyzing the newly diagnosed intracranial processes, we found a higher rate of hemorrhagic lesions in hematological patients and ischemic lesions in solid tumour patients. All patients were undergoing antineoplastic treatment at the time of ICU admission, i.e.: chemotherapy for hematological patients and chemotherapy, radiotherapy, or surgery for patients with solid tumours. Along with other recognized risk factors specific for critical illness (e.g., septic encephalopathy, residual sedation, immobilization, comorbidities), antineo-plastic treatment adds to risk factors for neurological complications. Hematologic malignancies and chemotherapy usually lead to thrombocytopenia and coagulation disorders, predisposing to intracranial bleeding. On the other hand, inflammation associated with antineoplastic treatments in solid tumours significantly increases ischemic risk in patients who already have a procoagulant status. These features explain the distribution pattern of abnormal radiologic findings among patients and seem to be related to their outcomes.

ICU physicians are often faced with the dilemma of selecting the most appropriate diagnostic test for their patients. CT is widely used in critically ill patients due to its availability, accessibility, no need for compatible devices, and shorter duration, and is indicated for many clinical reasons in a wide range of suspected pathology.10 Cerebral magnetic resonance imaging (MRI) is a superior diagnostic tool for critically ill patients with neurological disturbances. Compared with CT, MRI has an increased diagnostic sensitivity for acute stroke, neoplasms, infections and encephalopathy due to hypoxia, sepsis, uremia, hyperammonemia, glucose and sodium abnormalities.12 Comparing CT and MRI performed in critically ill patients during the same ICU admission, the MRI diagnostic yield was better by 33%, but changed the CT based working diagnosis for only 4.4% of patients.11 In addition, MRI has numerous safety challenges in ICU patients, the particular one being the need for MRI-compatible monitoring and life-support equipment. Considering the risk-benefit ratio, MRI indications in critically ill patients should probably include request for additional assessment of CT findings and evaluation of patient with persistent neurologic symptoms despite a normal/equivocal CT.

The associated risks and costs of every investigation must be weighed against the failure of a correct diagnosis. Moreover, in oncological patients, it is difficult to keep a good balance between under- and over-imaging, mainly in the case of nonspecific clinical signs. Our results support the need for systematic EHCT in the subgroup of critically ill hemato-oncological patients with AMS.

In our study, we recorded very low scanning rates when compared to published data (4% vs. 10.7–33%).2,3,7,9,12 There are several explanations for this seemingly under-investigation. In contrast to other published studies, we analyzed only EHCTs indicated during ICU stay in oncological patients admitted with non-neurological diagnosis. Namely, we analyzed only EHCTs that were indicated for new neurological signs developed during ICU admission. The high risks associated with transport and CT examination in unstable oncological patients should be weighed against the benefits in terms of prognosis and therapeutic options.

Complications involving the central nervous system are frequently encountered in critically ill patients. In the literature, when present, they nearly double the risk of ICU mortality (55% vs. 28.5% in patients without neurological complications).13 Similarly, in our study, the outcomes of patients with EHCTs were worse than of patients without brain scans, thus, without neurological impairment.

We found that half of the EHCTs were positive, which was higher than reported by other published retrospective studies (8%–37%).2,3,7, 8, 9, 10 This difference can be explained by the above mentioned study design specificities.

Beyond the number of positive EHCTs, it is worth analyzing their distribution according to clinical indication. The occurrence of FND or seizures is an undisputable EHCT indication. Whether new AMS requires EHCT is debatable. In critically ill patients, AMS is a frequent condition and could indicate an acute intracranial process, but much more commonly is the consequence of systemic conditions (e.g., medications and their interactions, metabolic impairments, sepsis, renal, hepatic, or electrolytic disturbances). Therefore, AMS is probably becoming an important topic in research: two recent studies8,10 included only patients with AMS, while another two3,7 found AMS to be the clinical indication in 70% and 88% of cases (though with a lower rate of positive CTs, in 7.5% and 22.8% cases, respectively). Critically ill oncological patients have certain particularities, with sepsis being the most common cause of ICU admission; this increases both the probability of septic encephalopathy and the risk of acute intracranial processes. Hemato-oncology patients are often admitted with severe neutropenia and thrombocytopenia and represent a specific subgroup due to their extremely high risk of septic, hemorrhagic and/or ischemic complications. Brain metastases or leukemic infiltration, which are associated with cerebral oedema, may also be present. These conditions make it difficult to assess the risks and benefits correctly in critically ill haemato-oncological patients. Our data revealed a higher probability of abnormal findings on scans performed for AMS in oncological ICU patients, suggesting that physicians should have a low threshold indicating EHCT for this group.

In the present study, the two main changes identified using CT were acute ischemic and hemorrhagic lesions. While the prevalence of ischemic stroke was comparable with literature data (25– 62%)10,12, the prevalence of hemorrhagic lesions was close to the highest percentage reported (40%).10,12 Limited published data in critically ill cancer patients indicate that approximately 18%, who underwent brain CT for acute neurologic symptoms and signs, had intracranial hemorrhage.13

EHCT and positive EHCT indicated for AMS show similar distribution between hematological and solid tumours. For positive EHCT, the type of newly occurred intracranial processes varies greatly between hematological (mainly hemorrhagic lesions) and solid tumour patients (mainly ischemic lesions). This distribution pattern could be explained by the risk factors mentioned above.

In EHCT studied patients, we recorded a doubled mortality rate compared with the general mortality in ICU patients. However, the mortality rate in positive and negative EHCT patients was similar. In hematological patients, the difference in mortality was recorded between positive and negative EHCT, with higher values for those with AMS as the clinical indication. The mortality of our patients with intracranial hemorrhage was in line with that reported in other studies on critically ill cancer patients (78%)14 and in hospitalized non-oncological patients (81%).15,16

Several limitations of our study should be highlighted. Being a retrospective study, all data were collected from patients’ files, which could have led to missed or incomplete information. The cohort size might be considered another limitation, as our study group was smaller than others.2,3,6,7,9 While the cited studies were conducted on medical, surgical, or mixed ICU patients with or without previous neurological pathology, we included only critically ill oncological patients with new neurological signs occurring during ICU admission. Also, only a fraction of the EHCT performed in our patients were contrast-enhanced due to various contraindications.

In oncological critically ill patients, the diagnostic yield of EHCT is much higher than in other categories of ICU patients. AMS, a clinical sign usually produced by multiple causes, should be a red flag announcing the presence of a new intracranial pathologic process in this specific group of patients. The results of our study support the systematic use of EHCT examination for emerging AMS, as it may identify intracranial complications early, particularly bleeding in hemato-oncological patients.