Page 870 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 68: Approach to Infection in Patients Receiving Cytotoxic Chemotherapy for Malignancy 601

active myelosuppressive cytotoxic therapy, since this represents the In order to gain control of these progressive malignant processes,
largest group of immunocompromised patients who will require critical prompt administration of cytotoxic therapy in the ICU setting may
care services. Infections in patients with the acquired immunodeficiency be necessary. Under such circumstances, the 30-day all-cause mortal-
syndrome (AIDS) are discussed in Chap. 69, and infections in those with ity has been associated with requirement for vasopressors, mechanical
organ or bone marrow transplantation are discussed in Chaps. 94 and 115; ventilation, and hepatic failure. As for noncancer patients, the 30-day
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the problem of lung infiltrates in immunocompromised patients is all-cause mortality increases with the number failing organs.
covered in Chaps. 65 and 69. The 30- and 180-day all-cause mortality rates for cancer patients
Hematologists and oncologists have long recognized the existence of receiving primary cytotoxic therapy in the ICU have been reported to be
the direct relationship between dose and response in cancer therapy. of the order of 40% and 60%, respectively. 16,17 The 30-day mortality rates
Over the last 10 to 15 years, the supportive care strategies for cancer are lower among patients with solid tumors compared to those with
patients undergoing remission-induction or salvage therapy have hematological malignancies but similar to those ICU patients without
improved sufficiently to permit the extension of dosing to the very limits a cancer diagnosis. Overall, these observations have demonstrated
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of toxicity and beyond. For many malignant diseases, this has translated that the administration of primary antineoplastic therapy in the ICU
into significantly higher response rates and disease-free survival. Cure to critically ill cancer patients is feasible and may be associated with
is now a goal that can be adopted realistically for many more patients significant chances of survival. In contrast, administration of cytotoxic
with these diseases. therapy in the ICU setting as salvage therapy to patients with relapsed
cancer has been associated with prolonged survival in less than 10% of
cases. Accordingly, the benefit of ICU-based cytotoxic therapy may be
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CANCER PATIENTS IN THE ICU restricted to those at first presentation of cancer.
A greater number of cancer patients are being considered for admission Three broad categories of admission criteria to ICU for cancer
to ICU for the management of critical illnesses developing as a func- patients have been offered: postoperative care, management of medical
tion of the underlying caner or of its treatment. Combined modalities emergencies related to cancer or its treatment, and monitoring during
3
10
of anticancer treatment including aggressive surgical diagnostic and intensive anticancer treatments. The most common circumstances
tumor debulking procedures, and targeted radiotherapeutic and sys- in which cancer patients may require access to ICU services include
temic therapies have resulted in significant improvements in overall (1) respiratory failure, (2) postanesthetic recovery, (3) infection and
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survival. During the years 1984 to 2000, hospital mortality rates for sepsis, (4) bleeding, and (5) oncologic emergencies. Groeger and
4,5
cancer patients admitted to ICU for mechanical ventilation were 70% Aurora described three principles upon which decisions about deploy-
to 85% and even higher, 95%, for hematopoietic stem cell transplant ment of ICU services for cancer patients occur. First, the intensive
(HSCT) recipients requiring mechanical ventilation. Accordingly, care clinician, in consultation with the referring cancer specialist and
6,7
cancer patients with critical illnesses have been at high risk for refusal the patient, must try to balance the likelihood of survival from the
for admission to an ICU setting. 8 critical illness against survival from the underlying malignancy. Second,
Recent experience has been more encouraging, however. Investigators the intensivist must understand whether the patient’s autonomy and
began reporting reductions in the hospital mortality rates among expressed wishes are being respected as would be articulated in an
cancer patients admitted to an ICU from 25-50% early this decade. advance care plan. Third, in the circumstances of limited resources the
7,9
10
Improved outcomes may be, in part, attributable to improved medical principle of distributive justice should be considered. As a framework
technologies such as noninvasive mechanical ventilation in the ICU and to aid in the discussion of goals of care for cancer patients, including
to better anticancer treatment, but also upon a better understanding of those suffering from a critical illness for which ICU services may be a
relevant prognostic factors contributing to outcome. The most impor- consideration, Haines and colleagues classified patients in five categories:
tant variable affecting prognosis and outcome for cancer patients is the (1) those with newly diagnosed cancers, (2) those with a cancer diag-
status of the underlying malignancy at the time of ICU admission. 10,11 nosis with the potential for cure, (3) those with controlled but incurable
Critical illness developing in patients with poor premorbid performance malignancy, (4) those who have failed specific treatment designed for
status and chronic end-organ damage in the setting of metastatic cancer cure or control, and (5) those being managed with palliative intent
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represent a composite with the poorest overall outcome. 8,12 for symptom control. Based on this classification, types 1 and 2 cancer
Cancer patients have represented 9% to 15% of all patients admitted to patients almost always would be candidates for ICU services, types 3 and
general ICUs in Europe. 13,14 Of these, solid tissue malignancies have con- 4 may be evaluated for such services on a case-by-case basis, and type
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stituted the majority (85%) and hematological malignancies comprised 5 patients would not be candidates. An algorithm guiding decision
the remainder. Patients with hematological malignancies are more making is offered for consideration in Figure 68-1.
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often admitted to the ICU with sepsis, whereas patients with solid tissue
malignancies are more often admitted after surgery. Hematological
malignancy patients are more severely ill than their solid tumor coun- DEFICITS IN HOST DEFENSES RELATED
terparts or those without cancer as measured by admission SOFA and TO CANCER CHEMOTHERAPY
SAPS II scores. Neutropenia upon ICU admission does not, in of itself, ■
14
appear to affect outcome unless there is no myeloid reconstitution. 15 MYELOSUPPRESSION AND NEUTROPENIA
Patients with newly diagnosed cancer may develop critical illness The absolute number of circulating segmented neutrophils (ANC) repre-
due to infection or cancer-related end-organ damage that requires ICU sents the most important single parameter predictive of the risk for life-
support prior to antineoplastic therapy. Invasive bacterial or fungal threatening pyogenic infection. An ANC of 1.5 to 8.0 × 10 /L can be
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9
infections often occur in the setting of cancer-related myelosuppression considered normal for adults. As the ANC declines below 1.0 and 0.5 ×
with severe neutropenia due to myelophthisic processes, and opportu- 10 /L, the risk of infection increases, with greatest risk for bacteremic
9
nistic infections due to intracellular pathogens occur as consequence of infection at neutrophil counts below 0.1 × 10 /L. For consistency, the
9
disease-related immunosuppression with severe lymphopenia or func- terms severe and profound neutropenia refer to ANCs below 0.5 × 10 /L
9
tional hypogammaglobulinemia. Cancer-driven end-organ damage may and 0.1 × 10 /L, respectively. Figure 68-2 illustrates the relationship
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9
include leukemic pulmonary leukostasis, intracranial lesions with mass between the neutrophil count and infection for patients undergoing
effect, spontaneous acute tumor lysis syndrome, disseminated intra- remission-induction therapy for acute leukemia.
vascular coagulation, hemophagocytosis syndrome, superior vena cava The ANC is calculated by multiplying the proportion of white blood
syndrome, malignant pleural or pericardial effusions, or bulky tumor cells (WBCs) that are segmented neutrophils on a Romanovsky-stained
masses with erosive effects upon vital structures. blood smear by the total number of WBCs in a specified volume of

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