Chemotherapy is one of the main measures of tumor treatment, and most of the toxic side effects caused by chemotherapy drugs can be prevented or reduced after active treatment. A recent review published by Lancet Oncol describes in detail the rare systemic emergencies caused by chemotherapy, and discusses their pathogenesis and treatment. A recent review published in Lancet Oncol details the rare acute diseases of various systems caused by chemotherapy and describes their pathogenesis and treatment. The review did not address clinical emergencies associated with molecularly targeted agents. We believe that this review is worthy of careful study and mastery by oncologists, and we would like to share the highlights of this review with you.
Circulatory and respiratory emergencies
Fatal cardiac arrhythmias
Paclitaxel, anthracyclines, isocyclophosphamide, fluorouracil, gemcitabine, and cisplatin can cause arrhythmias.
Although benign arrhythmias often result after the application of anthracyclines, cases of malignant arrhythmias, such as ventricular tachycardia, Mohs II and complete AV block leading to sudden death of the patient, have been reported.
The acute arrhythmias caused by cisplatin are supraventricular and ventricular arrhythmias and bundle branch block. Two mechanisms contribute to the cardiotoxicity of cisplatin: (i) direct toxic effects on the myocardium; and (ii) electrolyte disturbances secondary to the drug. Therefore, the risk of cardiac arrhythmias must be reduced by actively correcting the patient’s low magnesium and potassium levels before and after cisplatin administration.
Cardiotoxicity of cyclophosphamide is rare, but when pretreated with high doses of cyclophosphamide for bone marrow transplantation, it can range from asymptomatic electrocardiographic changes to fatal arrhythmias with rapid and unpredictable onset. The mechanism of this may be due to direct damage to the myocardium by the drug. In addition, acute sympathetic excitation caused by cytotoxic drugs, followed by nausea, vomiting and water-electrolyte disturbances may be associated with the development of arrhythmias.
When patients experience syncope, palpitations and chest pain during chemotherapy, drug-related symptoms should be considered and an electrocardiogram should be performed immediately to clarify the presence or absence of arrhythmias. In case of drug-related arrhythmias, the drug should be discontinued immediately, and the associated water-electrolyte disturbances should be corrected promptly, and electrocardiographic monitoring should be performed for at least 24 hours. Once symptomatic arrhythmias occur, subsequent chemotherapy must be carefully selected for cytotoxic drugs.
Spontaneous pneumothorax
Although pneumothorax is a common complication of primary, metastatic lung cancer, it is rare as a chemotherapy emergency (incidence <1%) and is most often associated with chemotherapy-sensitive tumors, such as germ cell tumors, lymphomas, and sarcomas.
Spontaneous pneumothorax often occurs on days 2-7 after chemotherapy and is possible unilaterally and bilaterally. The mechanism may be due to lysis or necrosis of the tumor by cytotoxic agents, resulting in rupture of the peripheral zone alveoli, which communicates with the pleural cavity, bronchi, or both, with the possibility of fistula formation. The incidence of pneumothorax is increased in patients with underlying lung disease or who have received radiotherapy.
The possibility of spontaneous pneumothorax should be considered when patients develop dyspnea after chemotherapy. Depending on the volume of the pneumothorax, treatment should involve either puncture aspiration or closed chest drainage. The persistence of a pneumothorax is associated with fistula formation, which may require emergency surgery. The recurrence of pneumothorax must be guarded against in the follow-up chemotherapy.
Chemotherapy-associated acute pneumonia
Chemotherapy-associated acute pneumonia is rare and has a high mortality rate, with an acute onset of dyspnea and diffuse exudate throughout the lung. Bleomycin, methotrexate and cyclophosphamide are more likely to cause it.
Toxic reactions to bleomycin tend to occur in the lungs and skin because these organs lack the hydrolases that inactivate them. High doses of bleomycin can lead to bleomycin-associated pneumonia, which can progress to pulmonary fibrosis. In contrast, acute lung-related complications from small doses are very rare (incidence <1%). Bleomycin-associated pneumonia presents as either fatal interstitial pneumonia or a somatic-specific drug reaction. Both occur immediately or several hours later after dosing and usually occur with the 1st or 2nd dose of bleomycin.
Fatal interstitial pneumonia begins with a dry cough, dyspnea, and hypothermia, and progresses with pneumonia with progressively more complex symptoms of shortness of breath, dyspnea at rest, and hypoxia. Physical examination shows bursting sounds at the base of both lungs, which may progress to a dry sternotomy sigma woven 5chu stole from the patient. Pulmonary function tests are useful in assessing the severity of pneumonia. Approximately 1% of patients with lymphoma treated with bleomycin may develop a somatic-specific drug reaction with clinical manifestations of confusion, fever, chills, wheezing, or hypotension, similar to an allergic reaction.
The primary treatment for interstitial pneumonia is intravenous high-dose methylprednisolone or oral prednisolone (60-100 mg/d), while somatic-specific drug reactions involving the lungs require volume expansion, vasopressure, antihistamines, and high-dose steroid hormone therapy. Hypoxic patients can be treated with low concentration oxygen. High concentration oxygen can lead to the formation of oxygen radicals and aggravate lung injury, so high concentration oxygen therapy is not advocated. Follow up chemotherapy with bleomycin is not recommended.
Paclitaxel-associated pneumonia is common, but only three cases of paclitaxel-associated acute bilateral pneumonia have been reported, all of which occurred within 6 hours after one course of chemotherapy. The patients presented with acute dyspnea, dry cough and hypoxia, probably due to an acute hypersensitivity reaction. Follow-up treatment with paclitaxel-based drugs is not recommended.
For patients who present with acute dyspnea, dry cough and hypoxia after chemotherapy, chemotherapy-associated pneumonia should be considered after excluding infection, and chemotherapy should be stopped after clear diagnosis. Chest X-ray can help in diagnosis, and high-resolution CT examination is feasible if available. Once chemotherapy drug-associated pneumonia is suspected, immediate treatment with high-dose steroid hormone (prednisolone 60-100 mg/d) is indicated, because hormone therapy is effective only during the acute inflammatory phase. If the patient continues to deteriorate after these treatments and develops persistent hypoxia, acute respiratory distress syndrome (ARDS) must be considered at this time. Most patients with chemotherapy-associated pneumonia respond well to hormone therapy, but the dose should be carefully and slowly tapered to prevent relapse.
Acute respiratory distress syndrome (ARDS)
ARDS is a severe clinical syndrome with rapid onset of dyspnea with intractable hypoxemia and diffuse pulmonary exudates, caused by different lung injuries, with a mortality rate of 40% to 65%. Gemcitabine, cytarabine, cyclophosphamide, methotrexate, and docetaxel have been reported to cause ARDS.
Most patients present with progressive dyspnea of acute onset after chemotherapy, but the time of onset varies widely. Gemcitabine-induced ARDS can occur up to 11 days after the last dose and occurs after several courses of treatment. Gemcitabine mostly causes mild respiratory symptoms, with transient dyspnea occurring in 8-10% of patients, but ARDS rarely occurs.
The diagnostic criteria for ARDS are intractable hypoxia, typical imaging (diffuse exudative shadow in both lungs on chest radiograph), and no clinical evidence of left heart failure. Patients mostly require mechanical ventilation and supportive therapy, and many have been treated with antibiotics before infection is completely ruled out, and most have also been treated with diuretics and steroid hormones, with some patients improving rapidly after hormonal therapy. However, even after these treatments, mortality remains high, and autopsy may reveal alveolar wall inflammation with abnormal permeability. It is advisable to stop chemotherapy immediately if progressive dyspnea worsens in chemotherapy patients, and subsequent chemotherapy should not be followed by the same drugs again.
Hematologic emergencies
Acute hemolytic anemia
Acute hemolytic anemia is associated with a variety of cytotoxic drugs, such as fludarabine, cisplatin, carboplatin and oxaliplatin. Patients present with acute back pain, fever and chills, symptoms of anemia (dyspnea, increased heart failure) and hemolysis (jaundice, deepening urine color) during or shortly after drug administration. Laboratory tests showed a decrease in isolated hemoglobin (Hb), normal white blood cell (WBC) and platelet counts (BPC), and a decrease in bead protein concentration, suggesting hemolysis. Blood smear showed few ruptured red blood cells (<1%) and a significant increase in spherical red blood cells. Lactate dehydrogenase, bilirubin, and creatinine concentrations are elevated. Indirect antiglobulin or Coomb's test is negative, direct antiglobulin test is positive, and specific anti-IgG antibodies are present.
Early treatment includes immediate cessation of chemotherapy, massive fluid infusion, anti-infection, etc. Blood transfusion is required to maintain Hb concentration >8 g/L and close monitoring of renal function, plasma biochemical parameters and urine output to prevent hemolytic-uremic syndrome. If the patient’s condition continues to deteriorate after the above active treatment, high-dose steroid hormone (intravenous methylprednisolone 500 mg/d) treatment and plasma exchange may be given. Re-chemotherapy with the same chemotherapeutic agent is strictly prohibited.
Acute thrombocytopenia
Because thrombocytopenia can result from either myelosuppression after chemotherapy or from bone marrow infiltration in malignant disease, drug-induced immune-related acute thrombocytopenia is easily overlooked. Platinum (especially oxaliplatin), cyclophosphamide, irinotecan, actinomycin D, and fludarabine mostly contribute to this acute condition, and they cause thrombocytopenia by stimulating specific immunoglobulin production that recognizes and binds to specific platelet membrane glycoproteins.
Patients present clinically with skin petechiae or bleeding, usually occurring within a few hours to 48 hours after drug administration. Complete blood counts show a rapid decrease in platelets, while Hb and WBC counts are normal. Immune-associated thrombocytopenia may be accompanied by immune-mediated hemolysis, so the Hb count may also be decreased, but other diagnoses such as diffuse intravascular coagulation (DIC) must be excluded. Bone marrow aspiration is mostly suggestive of normal megakaryocyte count and function, but this is not one of the criteria for confirming the diagnosis, and a definitive diagnosis can be made by flow cytometry for drug-dependent antibodies.
Thrombocytopenia, with or without acute hemolysis, should be considered as a possible chemotherapeutic drug-associated acute thrombocytopenia in the first few hours after chemotherapy, when cytotoxic drugs should be discontinued immediately and routine blood and coagulation tests should be performed. Platelets must be transfused to ensure that the patient’s BPC is within the safe range: >50×109/L if there is active bleeding, >20×109/L if there is fever, and >10×109/L if there is no bleeding or fever. Even after the platelets are normalized, antibodies are still present in the patient’s plasma, so it is not recommended to use the same chemotherapy drugs again.