Critically ill patients with cancer: A clinical perspective

Table 1 Reasons for intensive care unit admission in patients with cancer[15]

Cause	Comment
Postoperative care	Elective or emergency
Acute respiratory failure	(1) Infectious: Bacterial, viral, fungal; and (2) Noninfectious: Diffuse alveolar hemorrhage, interstitial lung disease, pulmonary drug toxicity, transfusion-related acute lung injury
Cardiovascular disorders	Sepsis and septic shock, pulmonary embolism, drug-induced cardiomyopathy
Bleeding disorders	Tumor erosion, coagulopathy, thrombocytopenia
Alteration of mental status	(1) Metabolic: Sepsis, drugs, multiorgan system failure, seizure, hyponatremia, hypoxia, hipercapnea; (2) Mass effect: Central nervous system bleeding, tumor effects; and (3) Others: Posterior reversible encephalopathy syndrome
Oncologic emergency	Tumor lysis syndrome, leukostasis, superior vena cava syndrome, cardiac tamponade, hipercalcemia
Acute decompensated chronic comorbidity	Chronic obstructive pulmonary disease, cardiac disorders (e.g., cardiomyopathy, coronary artery disease), chronic kidney disease, chronic hepatopathy
Others	Initiation of chemotherapy for surveillance

Table 2 Incidence and mortality of acute respiratory failure in cancer patients[25]

	Incidence	Need for ICU admission	Hospital mortality
Hematological malignancy
Acute myeloid leukemia	22%-84 %	66%	45%
Acute lymphoblastic leukemia	7%-18.5%	12%-15%	38.5%
Lymphoproliferative diseases	8%	8%	40%-50%
Myelodysplastic syndrome	29.4%	20%	17%
Autologous hematopoietic stem cell transplant	3%-28%	42%	3%-55%
Allogeneic hematopoietic stem cell transplant	24%-30%	50%	51%
Prolonged neutropenia	8%-29.5%	11%-16%	5%-12%
Solid tumor
Lung cancer	26%-50%	100%	11.2%-60%
Other solid tumors	0.7%-10.3%	100%	6.1%-55%
Patients on immunotherapy	1.3%-3.6%	1.3%	-

ICU: Intensive care unit.

Table 3 Mechanisms and features of hypoxemia

Mechanism	PaO2	PaCO2	DA-aO2	Comments
Disorders in oxygen diffusion	↓	↓	↑	Decreased surface area or short time for hematosis (e.g., hydrostatic edema, interstitial pneumonia, drug-associated interstitial lung disease, high-degree metastasized lungs)
Ventilation/ perfusion mismatch	↓	↑	↑	(1) Decreased ventilation in normally perfused lung regions (e.g., pulmonary infiltrates, pneumonia, atelectasis); and (2) Declined perfusion in normally ventilated lung areas (e.g., pulmonary embolism)
Increased intrapulmonary shunt	↓	↓	↑↑	Pulmonary venous blood bypasses ventilated alveoli without be oxygenated (e.g., acute respiratory distress syndrome)
Hypoventilation	↓	↑↑	N	Hypoventilation
Decrease in pressure of inspired oxygen	↓	↓	N	Decreased pressure of inspired oxygen

Table 4 Causes of acute respiratory failure in patients with cancer[35]

CNS and neuromuscular disorders	Chest wall and pleural disorders	Vascular disorders	Airway disorders	Parenchymal disorders
Drug intoxications: Narcotics; Sedatives; Neuroleptics	Pleural disorder: Malignant pleural effusion; Pleural tumor (primary or metastatic); Tension pneumothorax	Acute pulmonary embolism; Tumor embolism; Pulmonary venooclusive disease	Airway obstruction: Endobronchial metastases; External airway compression; Primary tumor of periglottic area	Pneumonitis: Infection; Chemotherapy; Radiotherapy; Aspiration
Encephalopathies: Infection; Metabolic; Seizure	Chest wall disorders: Chest wall tumor (primary or metastatic); Rib fracture		Others: Tracheoesophageal fistula; Bronchiolitis obliterans	Acute respiratory distress syndrome: Infection; Chemotherapy; Radiotherapy; Transfusion
Intracranial tumors: Primary; Metastatic				Complications of HSCT: Peri-engraftment respiratory distress syndrome; Diffuse alveolar hemorrhage; Idiopathic pneumonia syndrome
Neuropathies/myopathies: Nerve palsy				Others: Lymphangitic carcinomatosis; Pulmonary leukostasis; Bronchiolitis obliterans organizing pneumonia
Paraneoplastic syndromes: Eaton-Lambert syndrome; Myasthenia gravis; Guillain-Barré syndrome

CNS: Central nervous system; HSCT: Hematopoietic stem cell transplant.

Table 5 Invasive and noninvasive diagnostic procedures in cancer patients with acute respiratory failure[5]

Diagnostic procedure	Comments
Blood cultures	Hospital-acquired bacteria
Multislice or high-resolution CT scan	In most cases without contrast media; MRI if a pulmonary CT scan is not feasible
Echocardiography	Cardiac evaluation
Sputum examination	Bacteria; Fungi; Mycobacteria
Induced sputum	Pneumocystis jiroveci
Nasopharyngeal aspirates or nasal swabs	Adenovirus, metapneumovirus, coronavirus, parainfluenza virus types 1, 2, 3 and 4; influenza virus types A and B, respiratory syncytial virus A and B; rhinovirus A, B, and C; bocavirus and enterovirus
Polymerase chain reaction blood test	Herpesviridae; Cytomegalovirus; Epstein-Barr virus
Circulating Aspergillus galactomannan	Aspergillus spp.
Serologic tests	Chlamydia pneumoniae; Mycoplasma pneumoniae; Legionella pneumophila
Urine antigen	Legionella pneumophila; Streptococcus pneumoniae
BAL (mandatory)	(1) Cytospin preparation including Giemsa stain for cytological diagnostics and Gram stain; (2) Quantitative or semi-quantitative bacteriological cultures including culture media to detect Legionella spp., mycobacteria and fungi; (3) Calcofluor white or equivalent stain (assessment of fungi); (4) Quantitative (if possible) PCR for Pneumocystis jirovecii; (5) Direct immunofluorescence test for Pneumocystis jirovecii; (6) Aspergillus antigen (Galactomannan ELISA); and (7) Mycobacterium tuberculosis PCR, atypical mycobacteria
BAL (optional)	(1) PCR for cytomegalovirus, respiratory syncytial virus, influenza A/B virus, parainfluenza virus, human metapneumovirus, adenovirus, varicella zoster virus, and Pneumocystis jirovecii (quantitative); and (2) Aspergillus antigen (Galactomannan ELISA); Panfungal or Aspergillus/ mucormycetes PCR
Transbronchial biopsies	Not recommended in general in febrile neutropenic and/or thrombocytopenic patients as the first line procedure

CT: Computed tomography; BAL: Bronchoalveolar lavage; PCR: Polymerase chain reaction.

Table 6 Risk-stratification tools for patients with febrile neutropenia[54,60-62]

Description/Criteria	Group/ Points
Talcott classification system
Patients hospitalized at onset of fever and neutropenia (inpatient at presentation)	1
Outpatients at presentation but with comorbidities which require hospitalization	2
Outpatients at presentation with uncontrolled cancer but without comorbidities	3
Outpatients at presentation without comorbidities and controlled cancer	4
Multinational association of supportive care of cancer (MASCC) risk-index
Burden of febrile neutropenia
No or mild symptoms: No fever, hemodynamic compromise or clinically significant signs and symptoms of particular site of infection	5
Moderate symptoms: Any others not included in mild or severe symptoms	3
Severe symptoms: High grade fever, any hemodynamic compromise or any of the serious complications requiring high dependency unit support	0
No hypotension (systolic blood pressure > 90 mmHg)	5
Solid tumor or hematological malignancy with no previous fungal infection	4
No chronic obstructive pulmonary disease	4
No dehydration requiring parenteral fluids	3
Outpatient status	3
Age < 60 yr	2
Clinical Index of Stable Febrile Neutropenia (CISNE) score
Eastern Cooperative Oncology Group performance status ≥ 2	2
Stress-induced hyperglycemia	2
Chronic obstructive pulmonary disease (on steroids, supplemental oxygen, or bronchodilators)	1
Chronic cardiovascular disease (excluding single uncomplicated episode of atrial fibrillation)	1
Mucositis (at least the presence of patchy ulcerations or pseudomembranes, or moderate pain with modified diet)	1
Monocytes < 200 cells/mm3	1

Table 7 Empiric antibiotic therapy in high-risk patients with febrile neutropenia[40,54,55,79,83]

Antibiotherapy	Indication
Antipseudomonal β-lactam agent (cefepime, ceftazidime)	All patients with febrile neutropenia
OR
Carbapenem (meropenem or mipenem/cilastatin)	Hemodynamic instability
OR
Piperacillin/tazobactam
OR
Novel cephalosporin/β-lactamase inhibitor (Ceftolozane/tazobactam or Ceftazidime/avibactam)
PLUS
Aminoglycosides (optional)
PLUS
Vancomycin
Vancomycin, linezolid or daptomycin	Suspected catheter-related infections
	Skin or soft-tissue infection
	Risk of methicillin-resistant Staphylococcus aureus
Linezolid or daptomycin	Risk of vancomycin-resistant Enterococcus spp.
Carbapenem	Risk of extended-spectrum β-lactamase-producing gram negative bacteria
Polymyxin-colistin or tigecycline	Risk of Klebsiella pneumonia carbapenemase
Ciprofloxacin + clindamycin	Penicillin-allergic patients
OR
Aztreonam + vancomycin
Trimethoprim/sulfamethoxazole	Suspected Pneumocystis pneumonia
Antifungal drugs (echinocandins, amphotericin B lipid-based formulations)	Suspected invasive mycosis

Table 8 Main cardiovascular complications of oncological therapy[91,92]

Cardiovascular complications	Types	Oncological therapies
Left ventricular dysfunction	Cardiomyopathy or myocarditis	Anthracyclines (e.g., doxorubicin, aunorubicin, epirubicin, idarubicin), antiangiogenic agents (e.g., bevacisumab, sunitinib, sorafenib), alkylating agents (e.g., cyclophosphamide, cisplatin), monoclonal antibodies (e.g., trastuzumab, lapatinib), tyrosine kinase inhibitors (e.g., imatinib, dasatinib, nilotinib, sunitinib, sorafenib, lapatinib)
Arrhythmias	QT prolongation, bradycardia, heart block; Atrial arrhythmias; Ventricular arrhythmias or sudden cardiac death	Taxanes, arsenic trioxide, tyrosine kinase inhibitors (e.g., imatinib, dasatinib, nilotinib, sunitinib, sorafenib, lapatinib), anthracyclines(e.g., doxorubicin, aunorubicin, epirubicin, idarubicin)
Coronary artery disease	Acute coronary syndromes (included acute myocardial infarction); Chronic ischemic heart disease	Antimetabolites (e.g., gemcitabine, cytarabine), cisplatin, taxanes, thalidomide, bevacisumab, radiotherapy
Pericardial disease	Pericarditis (effusive or constrictive form)	Radiotherapy
Hypertension	New-onset or worsening	Vascular endothelial growth factor inhibitors, antiangiogenic agents (e.g., bevacisumab, sunitinib, sorafenib), cisplatin, interleukins, interferon

Table 9 Immunological effects of opioids

Opioids	Immunological effects
Morphine	Decreased NK cell cytotoxicity[131]; Impaired intestinal barrier function[140]
Fentanyl and sufentanil	Decreased NK cell cytotoxicity[141]; Inhibition of cellular and humoral immunity[141]
Tramadol	Reverse the immunosuppression after surgery[142]

NK: Natural killer.

Table 10 Causes of cancer-related seizure and cancer-related acute hydrocephalus[158]

Causes	Comments
Cancer-related seizure
Low-grade tumors	Glioma and oligodendroglioma have intrinsic epileptogenic activity as a result of their long survival and reduced seizure threshold
High-grade tumors	Usually secondary to necrosis, hemorrhage or edema
Brain metastases	Up to 40%
Tumor location	Cortical tumors and those on epileptogenic areas (e.g., mesial temporal lobe and insula) are associated with intractable epilepsy
Stroke	Ischemic or hemorrhagic
Drug toxicity	Cytarabine, methotrexate, cisplatin, vincristine, cyclophosphamide, anthracyclines
Neoplastic meningitis
Paraneoplastic encephalitis
Central nervous system infections
Electrolytic imbalance	Hyponatremia, hypocalcaemia
Metabolic disorders	Hypoglycemia
Liver or kidney failure
Aggravated preexisting epilepsy	Withdrawal medication
Cancer-related acute hydrocephalus
Stopped CSF flow by tumor obstruction of ventricular system	Colloid cysts, ependymoma, intraventricular meningioma, choroid plexus papilloma or posterior fossa tumor; in adults it is often due to leptomeningeal carcinomatosis and intra-ventricular extension of metastasis
Increased CSF content due to deficit in reabsorption	Venous sinus thrombosis, infectious meningitis, metastatic seeding or subarachnoid hemorrhage

CSF: Cerebrospinal fluid.