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Objectives: To describe the most common serious adverse effects and organ toxicities associated with emerging therapies for cancer that may necessitate admission to the ICU., Data Sources and Study Selection: PubMed and Medline search of relevant articles in English on the management of adverse effects of immunotherapy for cancer., Data Extraction and Data Synthesis: Targeted therapies including tyrosine kinase inhibitors, monoclonal antibodies, checkpoint inhibitors, and immune effector cell therapy have improved the outcome and quality of life of patients with cancer. However, severe and life-threatening side effects can occur. These toxicities include infusion or hypersensitivity reactions, cytokine release syndrome, pulmonary, cardiac, renal, hepatic, and neurologic toxicities, hemophagocytic lymphohistiocytosis, opportunistic infections, and endocrinopathies. Cytokine release syndrome is the most common serious toxicity after administration of monoclonal antibodies and immune effector cell therapies. Most of the adverse events from immunotherapy results from an exaggerated T-cell response directed against normal tissue, resulting in the generation of high levels of proinflammatory cytokines. Toxicities from targeted therapies are usually secondary to "on target toxicities." Management is largely supportive and may include discontinuation of the specific agent, corticosteroids, and other immune suppressing agents for severe (grade 3 or 4) immune-related adverse events like neurotoxicity and pneumonitis., Conclusions: The complexity of toxicities associated with modern targeted and immunotherapeutic agents for cancer require a multidisciplinary approach among ICU staff, oncologists, and organ specialists and adoption of standardized treatment protocols to ensure the best possible patient outcomes.

Hypersensitivity reactions are defined as immunologically based adverse reactions to chemicals or medicinal agents. These reactions are common in the intensive care unit and can present as a simple, mildly symptomatic rash or as life-threatening anaphylactic reactions. Hypersensitivity reactions have traditionally been classified as types I to IV reactions based on the underlying immune mechanisms, although the clinical relevance of the classification is unclear, and new subtypes to this system have been recently proposed. Given the immunologic and often unpredictable nature of these reactions, avoidance or prevention is not a feasible option. Therefore, management has primarily consisted of withdrawal of potential offending agents, supportive therapy, symptomatic management, and, in some specific examples, targeted pharmacotherapy. This article outlines the background and types of hypersensitivity reactions and provides descriptions and management strategies when applicable to common types of hypersensitivity reactions encountered in the intensive care unit.

Disorders of coagulation are common adverse drug events encountered in critically ill patients and present a serious concern for intensive care unit (ICU) clinicians. Dosing strategies for medications used in the ICU are typically developed for use in noncritically ill patients and, therefore, do not account for the altered pharmacokinetic and pharmacodynamic properties encountered in the critically ill as well as the increased potential for drug-drug interactions, given the far greater number of medications ordered. This substantially increases the risk for coagulation-related adverse reactions, such as a bleeding or prothrombotic events. Although many medications used in the ICU have the potential to cause coagulation disorders, the exact incidence will vary based on the specific medication, dose, concomitant drug therapy, ICU setting, and patient-specific comorbidities. Clinicians must strongly consider these factors when evaluating the risk/benefit ratio for a particular therapy. This review surveys recent literature documenting the risk for adverse drug reactions specific to bleeding and/or clotting with commonly used medications in the ICU.

Hyperthermia is frequently seen in the intensive care setting and is associated with significant morbidity and mortality. It is often initially misdiagnosed as fever associated with infection. Atypical presentations of classic syndromes are common. Clinical suspicion is the key to diagnosis. Adverse drug reactions are a frequent culprit. Syndromes include adrenergic "fever," anticholinergic "fever," antidopaminergic "fever," serotonin syndrome, malignant hyperthermia, uncoupling of oxidative phosphorylation, and withdrawal from baclofen. This review describes the pathophysiology of hyperthermia, as distinct from fever, and the physiology, diagnosis, and treatment of serotonin syndrome, neuroleptic malignant syndrome, malignant hyperthermia, and baclofen withdrawal. Much of the available evidence regarding the treatment of these disorders is based on single case reports, case series, or animal models. Therapeutic modalities consist of identification/withdrawal of possible offending agent(s), support directed at lowering temperature and preventing/treating complications, as well as targeted pharmacologic therapy directed at the specific cause. Early recognition and treatment using a multidisciplinary approach are essential to achieve the best possible outcome.

Thrombocytopenia occurs in 15% to 58% of intensive care unit patients. The incidence varies based upon patient population, timing and frequency of platelet monitoring, and definition of thrombocytopenia. Up to 25% of acutely ill patients develop drug-induced thrombocytopenia. When drug-induced thrombocytopenia is suspected, nondrug related causes must be evaluated and excluded. Establishing the diagnosis of drug-induced thrombocytopenia is challenging, as hundreds of medications have been implicated. Medications commonly associated with drug-induced thrombocytopenia include glycoprotein IIb/IIIa inhibitors, cinchona alkaloids, antibiotics, anticonvulsants, and heparin. Once the diagnosis is suspected, clinicians should identify the start date of medications to assess the timeline of development. The likelihood of each medication causing thrombocytopenia must be evaluated. The risk vs. benefit of discontinuing the suspected medication and availability of alternative medications must be assessed. The role of corticosteroids, immune globulin, and plasmapheresis is uncertain. Once the offending agent has been discontinued, the overall prognosis is excellent. In the case of suspected or confirmed heparin-induced thrombocytopenia, an alternative anticoagulant should be initiated. Drug-induced thrombocytopenia should be documented in the medical record and reported according to institutional and national standards. This review focuses on immune-mediated drug-induced thrombocytopenia from medications commonly utilized in the critically ill patient.

The objective of this review is to characterize the mechanisms, risk factors, and offending pharmacotherapeutic agents that may cause drug-induced arrhythmias in critically ill patients. PubMed, other databases, and citation review were used to identify relevant published literature. The authors independently selected studies based on relevance to the topic. Numerous drugs have the potential to cause drug-induced arrhythmias. Drugs commonly administered to critically ill patients are capable of precipitating arrhythmias and include antiarrhythmics, antianginals, antiemetics, gastrointestinal stimulants, antibacterials, narcotics, antipsychotics, inotropes, digoxin, anesthetic agents, bronchodilators, and drugs that cause electrolyte imbalances and bradyarrhythmias. Drug-induced arrhythmias are insidious but prevalent. Critically ill patients frequently experience drug-induced arrhythmias; however, enhanced appreciation for this adverse event has the potential to improve prevention, treatment, patient safety, and outcomes in this patient population.

Critically ill patients are predisposed to drug interactions because of the complexity of the drug regimens they receive in the intensive care setting. Drugs may affect the absorption, distribution, metabolism, and/or elimination of an object drug and consequently alter the intended pharmacologic response and potentially lead to an adverse event. Certain disease states that afflict critically ill patients may also amplify an intended pharmacologic response and potentially result in an unintended effect. A team approach is important to identify, prevent, and address drug interactions in the intensive care setting and optimize patient outcomes.