Intensive Care Considerations of the Cancer Patient

Burden of Disease

The International Agency for Research on Cancer reported that the incidence of cancer in 2018 was estimated at 18.1 million new cases and 9.6 million deaths. The cumulative risk for developing cancer is 22% in men and 18.3% for women; 12.7% of men and 8.7% of women will die from the disease. Cancer incidence is predicted to continue to rise to 29.5% by 2040, and cancer deaths predicted to exceed 16 million by 2040 ; however, cancer survival has improved significantly over time. Death rates from all cancers in the United States from 2000 to 2014 decreased by 1.8% per year among men and by 1.4% per year among women. Comparing the periods between 1975 and 1977 and 2006 and 2012, the 5-year relative survival for cancer in all sites improved from 50.3% to 66.4%. The number of patients with malignancy admitted to the intensive care unit (ICU) ranges from 5% to 15%. In Scotland, approximately 5% of patients with solid organ tumors will be admitted to an ICU during the first 2 years of diagnosis. Surgical admissions will comprise 84%, of which 63% will be elective. At MD Anderson, a comprehensive cancer center in the United States, surgical ICU admissions represent 60% of all ICU admissions. The utilization rate of surgical patients requiring ICU care is approximately 18.9%. Head and neck surgery, and neurologic and gastrointestinal services represented 62% of the total ICU admissions.

Surgical Oncology Critical Care Outcomes

A large analysis of surgical ICU patients with cancer in West Scotland compared patients with and without cancer and found that surgical ICU patients with solid tumor diagnosis had an ICU mortality of 12.2% versus 16.8% ( P < 0.001) in those without cancer. The hospital mortality for those with cancer was 22.9% versus 28.1% ( P < 0.001). These patients were more likely to be admitted as a result of an elective admission to the ICU. For those patients with cancer requiring organ support, the ICU mortality was 18.6%, and the hospital mortality of those admitted emergently was 39.5%. A review of the Dutch National Intensive Care Evaluation (NICE) registry found that the most frequent underlying malignancies included colorectal cancer (25.6%), lung cancer (18.5%), and tumors of the central nervous system (14.3%). Reasons for admission included need for mechanical ventilation (24.8%) and vasopressors (20.7%). In the surgical intensive care population, oncologic patients have a favorable ICU and hospital mortality rate of 1.4% and 4.7%, respectively, following admission after elective surgery. Overall, those with cancer have comparable opportunity for recovery, and underlying malignancy should not disqualify acceptance to the surgical ICU. At MD Anderson, from 1994 to 2013 hospital mortality of surgical patients was 1.1% and 2.9% in the ICU.

ICU Resource Allocation and Admission Prioritization

In 2017 a consensus group representing the fields of critical care in cancer patients was assembled from German and Austrian Societies and made recommendations with regard to those with cancer. Three co-cohorts of patients were identified ( Box 39.1 ). Surgical patients, especially those receiving elective procedures, would most likely be encompassed in the category of receiving full ICU management.

Intensive care admission criteria and resource allocation must be adapted at the institution level. Local resources often dictate the provision of critical care; therefore the threshold for ICU admission at lower acuity organizations may be much lower. The Society of Critical Care Medicine guidelines for ICU admission, discharge, and triage provide a sustained review of considerations for the development of institutional and departmental policies regarding the appropriate level of care of patients referred to the ICU. Important concerns for making balanced decisions regarding patient assignment include patient interventions that can only be applied in the ICU, clinical expertise, patient condition, diagnosis, bed availability, evidence of stability, prognosis, and potential benefit. Matching the needs of the patient to the interventions and level of care available at an institution is often a fluid process. The Society of Critical Care Medicine has developed two tools to aid leadership and the practitioner in the allocation of resources and prioritization to available units. Table 39.1 provides a description of the components of care and how the level of care, patient needs, nursing-to-patient ratio, and potential interventions may align for the best interest of the patient.

Common Factors Affecting Patients Coming to the ICU

Patients arriving at the operating theater are likely to possess physiologic derangements secondary to their malignancy, or due to prior exposure to chemotherapy and newer targeted interventions including immuno- and biologic therapies. Frequently encountered factors complicating care include neutropenia and immunosuppression, thrombocytopenia, prothrombotic states, coagulopathic states, chemotherapeutic toxicities, malnutrition, and poor functional status.

Neutropenia and Immunosuppression

Neutropenia, defined as an absolute neutrophil count of less than 1500 cells per microliter, is a common complication of chemotherapy. Risk of infection increases with both severity and duration of neutropenia. ^, Among patients receiving myelosuppressive chemotherapy, the risk of developing neutropenic fever during the chemotherapy course is 13%–20%. ^, The Multinational Association of Supportive Care in Cancer (MASCC) index is a validated tool to identify a patient’s risk for complications associated with febrile neutropenia. The assessment is based on age, history, outpatient or inpatient status, clinical signs, severity of fever and neutropenia, and presence of medical comorbidities. Guidelines for prevention and treatment of neutropenic fever are outlined and supported by major societies.

Thrombocytopenia

Thrombocytopenia is a common complication in oncologic patients. In solid tumor patients receiving chemotherapy, the 3-month risk of developing chemotherapy-induced thrombocytopenia is 13% (platelet count <100 × 10 ⁹ /L), 4% with grade 3 (25 to <50 × 10 ⁹ /L), and 2% with grade 4 (<25 × 10 ⁹ /L). Etiology of thrombocytopenia in cancer patients includes direct chemotherapy effects, splenomegaly, bone marrow infiltration, disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura, immune thrombocytopenia, infections, and medications. Patients receiving gemcitabine or carboplatin-based chemotherapy regimens tend to have increased incidence of thrombocytopenia. Several societies have recommended platelet count thresholds and targets for those patients undergoing elective surgery or invasive procedures ( Table 39.2 ). Preoperative consultation and postoperative involvement of hematologic specialists are key for diagnostic evaluation and selecting appropriate interventions that may include platelet transfusions, procoagulants, antifibrinolytics, and thrombopoietin receptor agonists. ^,

Prothrombotic States

Cancer is a well-known prothrombotic state. Cancer patients have a 4 to 7-fold increased risk of venous thrombosis compared with the general population or patients without cancer. Incidence rate of venous thrombosis amongst all patients with cancer is estimated at 13 per 1000 person-years. Patients with cancer undergoing surgery are at increased risk of venous thromboembolism (VTE), the incidence of which is estimated at 1.3%–2.1% within 30 days with an annual prevalence of 4% following major cancer surgery. ^, Thrombotic events may manifest as VTE, arterial thrombosis, DIC, and thrombotic microangiopathy. In addition to standard patient risk factors for thrombosis, cancer-associated risk factors include site of cancer, stage of cancer, histology, time after diagnosis, surgical interventions, hospitalization, chemotherapy, exposure to vascular endothelial growth factor inhibitors, and the presence of central venous catheters. The American Society of Clinical Oncology (ASCO) updated guidelines for VTE in patients with cancer in 2019; these specifically address cancer patients undergoing surgery. The recommended approach includes unfractionated heparin or low-molecular-weight heparin. Risks of active bleeding, high bleeding risk, or other contraindications must be weighed with potential benefit. All cancer patients should be offered pharmacologic thromboprophylaxis to be started preoperatively and continued for at least 7 to 10 days. In patients undergoing major open or laparoscopic abdominal or pelvic surgery for cancer who have restricted mobility, obesity, history of VTE, or who have risk factors for VTE, a 4-week course of prophylaxis is recommended.

Coagulopathy

A state of hypocoagulopathy is less frequently encountered but can exist in the cancer patient. In addition to the more frequently encountered perioperative causes of coagulopathy, coagulation abnormalities secondary to hemorrhage, hemodilution, hemostatic factor consumption, exposure to anticoagulants and antiplatelet agents, renal disease, and liver disease, the oncologic patient may present with a variety of unique etiologies for the underlying cause of bleeding ( Box 39.2 ) . ^,

DIC in cancer generally presents as a subacute consumptive state or as acute DIC. Chronic DIC is typically seen in solid organ tumors of the lung, breast, prostate, colon, and rectum, which comprise the most frequent primary tumors. Approximately 7%–29% of solid organ malignancies experience DIC, of which bleeding occurs in 59%, while thrombosis occurs in 34%. ^, Acute DIC can be seen in 29%–32% of non APL acute leukemia. ^, DIC in acute leukemia predominantly presents with bleeding as opposed to thrombosis. Management of DIC in cancer can require a complex and thoughtful approach and requires consideration of the thrombotic versus bleeding potential. Involvement of a hematologist will be worthwhile. For those who are bleeding or need an invasive procedure, Box 39.3 outlines an approach. Promyelocytic leukemia often presents with a particularly severe form of DIC associated with enhanced fibrinolysis. Fifty-three percent of those with acute promyelocytic leukemia (APL) will present with some manifestation of bleeding: bruising, epistaxis, abnormal menstrual bleeding, hematuria, hemoptysis, hematochezia, or melena. The coagulopathy associated with APL is particularly responsive to early induction therapy, thus mitigating bleeding risk. White blood cell count at presentation is the most significant predictor of early hemorrhagic death and early thrombo-hemorrhagic death. Use of recombinant thrombomodulin has been proposed as a rescue therapy for DIC. ^,

Malnutrition

Malnutrition is generally considered present by the American Society of Parenteral and Enteral Nutrition when at least two of six indicators are present ( Box 39.4 ). Generally, 26.6%–51% of oncologic patients will have nutritional impairment with 4.5%–9% overtly malnourished. ^, Malnutrition is consistently prevalent among hospitalized patients and present in approximately 40% of oncologic patients. ^, Given that the prevalence of malnutrition in hospitalized patients to admitted the ICU for more than 48 h is 70%, the burden of malnutrition in critically ill surgical oncology patients is likely to be substantial.

Presence and degree of malnutrition can be affected by primary malignancy, metastases, prior and ongoing therapies, including chemotherapy and radiotherapy, prior surgeries, metabolic and mitochondrial derangements, procachexia cytokines and factors, homeostatic control in the central nervous system. ^, Severity of malnutrition was positively correlated with the stage of cancer.

For those patients receiving cancer therapies, the routine administration of total parenteral nutrition (TPN) is not recommended by the American Society of Parenteral and Enteral Nutrition (ASPEN) to all patients undergoing major cancer operations. These recommendations are due to the poor evidence to support the beneficial effects of parenteral and enteral nutrition in mortality and morbidity. In patients who are severely malnourished, there may be benefit with parenteral nutrition. ^, Additionally, there may be a role for nutrition support therapy beginning 7–14 days preoperatively in patients who have moderate and severe malnourishment. Recommendations for those patients who are critically ill and in their perioperative phase are not well delineated in the literature. The 2016 SCCM/ASPEN Guidelines for Nutrition Support Therapy in the Adult Critically Ill Patient provide a framework for those patients in the ICU. No guideline, however, can replace the multidisciplinary dialogue between the surgeon, intensivist, and dietitian while taking into consideration the patient and operation performed. Key recommendations include initiation of enteral feeding within 24–48 h, interventions to reduce aspiration, application of feeding protocols, and avoidance of gastric residual measurements in assessing tolerance.