Mechanism of Anaphylactoid Reactions: Improper Preparation of High-Dose Intravenous Cyclosporine Leads to Bolus Infusion of Cremophor El and Cyclosporine

1997 ◽  
Vol 31 (11) ◽  
pp. 1287-1291 ◽  
Author(s):  
Merry Liau-Chu ◽  
Jochen GW Theis ◽  
Gideon Koren

BACKGROUND: During a Phase I/II trial of high-dose intravenous cyclosporine, a high incidence of anaphylactoid reactions was observed. Epidemiologic investigations revealed that the occurrence of anaphylactoid reactions was significantly associated with improper mixing during preparation of the infusions. It was hypothesized that improper mixing during the preparation of the infusion may have caused initial bolus infusions of the vehicle, Cremophor EL. These inadvertent bolus infusions may have caused the anaphylactoid reactions. OBJECTIVE: To investigate the effect of different mixing techniques on the distribution of the components of cyclosporine concentrate for infusion: cyclosporine, Cremophor EL, and ethanol in the infusions administered to the patients. METHODS: Infusions were prepared in a similar fashion as those administered to study patients enrolled in a high-dose cyclosporine therapy protocol. Samples were collected at defined time points of the infusions. Concentrations of cyclosporine and Cremophor EL were spectrophotometrically determined; ethanol concentrations were measured enzymatically. RESULTS: Cyclosporine and Cremophor EL concentrations were up to ninefold higher than intended during the first 10 minutes of the infusions that were not appropriately mixed. In contrast, the concentrations of cyclosporine and Cremophor EL were similar to the intended concentrations in all of the well-mixed infusions. CONCLUSIONS: Inappropriate mixing of high-dose cyclosporine infusions can lead to initial bolus infusion of cyclosporine and Cremophor EL. Bolus infusions of Cremophor EL have been associated with anaphylactoid reactions. Thus, thorough mixing of high-dose cyclosporine infusions may be important to reduce the possibility of life-threatening anaphylactoid reactions.

1995 ◽  
Vol 13 (10) ◽  
pp. 2508-2516 ◽  
Author(s):  
J G Theis ◽  
M Liau-Chu ◽  
H S Chan ◽  
J Doyle ◽  
M L Greenberg ◽  
...  

PURPOSE An unusually high incidence of anaphylactoid reactions was observed during a phase I/II trial of high-dose intravenous cyclosporine (CsA) therapy to attenuate tumor multidrug resistance (MDR). Five of 21 children experienced severe anaphylactoid reactions shortly after initiation of the first or second CsA infusion. We hypothesized that improper dissolution of the vehicle Cremophor EL may have been a cause for these anaphylactoid reactions. METHODS All nurses who had administered intravenous CsA were interviewed regarding their technique of preparing the infusion and the occurrence of an anaphylactoid reaction. The responses were statistically analyzed. The effect of various mixing techniques on the distribution of Cremophor EL in the infusion was experimentally evaluated. Different mixing techniques were used to assess their effect on the distribution of Cremophor EL in the solution. RESULTS Analysis of the preparation techniques of the CsA infusion showed significant correlation between suboptimal mixing of CsA by nurses and the occurrence of anaphylactoid reactions (P = .02). Experimental simulation showed that suboptimal mixing results in an uneven distribution of Cremophor EL, which subsequently sinks to the bottom of the vial. CONCLUSION Improper mixing of high-dose CsA infusions causes nonsolubilized Cremophor EL to sink to the outflow area of the bottle. An initial bolus infusion of highly concentrated Cremophor EL may produce an anaphylactoid-like response. This mechanism of toxicity is important to recognize, because it is easily preventable by proper preparation of the infusion, thus reducing the incidence of potentially life-threatening anaphylactoid reactions.


2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
O Oyende ◽  
J Jackman

Abstract Introduction Streptococcal myositis is a rare form of infectious myositis caused by Lansfield A beta-haemolytic streptococci. It is characterised by rapidly spreading inflammation that can result in severe systemic toxicity and necrosis of the affected tissue if not diagnosed and aggressively treated. Presentation We report a case of a 42-year-old male who presented with a one-week history of worsening right axillary swelling that progressed to painful swelling of his arm. Inflammatory markers were significantly elevated with a white cell count of 17 ×109/L and C-reactive protein of 212 mg/L. On examination, a fluctuant axillary swelling was appreciated, and a decision was made for incision and drainage under general anaesthetic. Intraoperative aspiration of his arm revealed copious purulent fluid prompting intraoperative orthopaedic consult and exploration of the anterior compartment in which there was extensive involvement of the biceps muscle. The microbiological analysis revealed gram-positive cocci in chains, and microbiology advice sought for tailoring of antibiotic regimen. He has recovered well. Discussion Though uncommon, the emergency general surgeon should have a high degree of suspicion when evaluating soft tissue infections to avert potentially disastrous outcomes. Conclusion Early diagnosis, aggressive management with high-dose intravenous antibiotics, and surgical debridement are principles to treat this rare, life-threatening infection.


2004 ◽  
Vol 327 (3) ◽  
pp. 152-155 ◽  
Author(s):  
Weng-Sheng Tsai ◽  
Chien-Ping Wu ◽  
Yu-Juei Hsu ◽  
Shih-Hua Lin

2017 ◽  
Vol 5 ◽  
pp. 2050313X1769599 ◽  
Author(s):  
Thomas J Reilly ◽  
Sean Cross ◽  
David M Taylor ◽  
Richard Haslam ◽  
Sophie C Tomlin ◽  
...  

Objectives: To describe a case of neuroleptic malignant syndrome following antipsychotic treatment of catatonia, highlighting the potentially serious complications of this rare adverse drug reaction. Methods: We present a case report of a patient who developed this syndrome with various sequelae. Results: The patient developed neuroleptic after being treated with lorazepam and olanzapine for catatonia. He subsequently developed the complications of rhabdomyolysis, acute kidney injury, pulmonary embolism, urinary retention and ileus. He received high-dose lorazepam, anticoagulation and intravenous fluids. Antipsychotic medication in the form of haloperidol was reinstated with no adverse effect, and he went on to make a full recovery. Conclusions: This case illustrates the potential life-threatening complications of neuroleptic malignant syndrome and the need for a low index of clinical suspicion. It also highlights the lack of evidence for treatment of catatonia, including the use of antipsychotics.


2021 ◽  
Vol 5 (6) ◽  
Author(s):  
Kyunghee Lim ◽  
Jong Sung Park ◽  
Byeol-A Yoon ◽  
Song-Hee Han

Abstract Background Necrotizing autoimmune myopathy is a rare subtype of idiopathic inflammatory myopathy; however, it can be associated with fatal cardiac manifestations. Case summary A 58-year-old female patient was referred for congestive heart failure with dysrhythmia. Electrocardiograms showed ventricular arrhythmias of various QRS complex morphologies and coupling intervals with beat-to-beat differences. Despite optimal medical therapy for heart failure, the patient was admitted for the progression of dyspnoea and generalized motor weakness. The burden of non-sustained ventricular tachycardia gradually increased, and ventricular fibrillation eventually occurred. In view of a differential diagnosis of an inflammatory myocardial diseases such as sarcoidosis, a cardiac biopsy was performed. However, pathologic examinations revealed only necrotic muscle fibres without granuloma. Further examinations revealed proximal dominant motor weakness, an elevated serum creatinine-phosphokinase level, myogenic potentials on needle electromyography, and biceps muscle biopsy findings that were compatible with necrotizing autoimmune myopathy. High-dose steroid therapy improved the patient’s motor weakness, including her respiratory impairment, and successfully suppressed ventricular arrhythmias. Discussion This case suggests that intensive immunosuppressive therapy with high-dose steroid could be useful in the necrotizing autoimmune myopathy manifested as congestive heart failure and life-threatening ventricular arrhythmias.


Author(s):  
Anjali Tarai ◽  
Kali Prasad Pattnaik ◽  
Kumar Haraprasad Mishra

Background: In Multi drug resistant falciparum malaria anti-malarial combinations are frequently used i.e. Quinine and IV Artesunate. Quinine is associated with electrocardiographic disturbances. Artesunate in high dose produce QTC prolongation in animal models, so the electrocardiogram (ECG) is thoroughly studied.Methods: Severe falciparum malaria cases 15 to 60 years were randomly allocated into 3 treatment regimens i.e. Artesunate, Quinine alone and their combination. Electrocardiographic recordings were taken periodically in 3 groups and compared statistically.Results: The mean QTC interval is significantly prolonged in combination treatment group from 0.40+0.02 to 0.49+0.09 (P<0.05) ECG disturbance (44%). QTC prolongation was commonest (i.e. 27%) with electrolyte imbalance could produce life threatening cardiac arrhythmia (Polymorphic VT with Sr K+ 2.9). Artesunate alone was list prone (i.e. only 6%) Quinine though has comparatively more (i.e. 25%) but there is no life-threatening cardiac arrhythmia in artesunate and Quinine.


2021 ◽  
pp. 1-3
Author(s):  
Emrah Erdogan ◽  
Murat Cap ◽  
Gorkem Kus ◽  
Cem Gokhan ◽  
Yakup Kilic

Abstract Allergic reactions related to drug use is a common entity presenting often from minor urticaria to life-threatening anaphylactoid reactions. A common but easily overlooked diagnosis, Kounis syndrome, is an established hypersensitivity coronary disorder induced by drugs, foods, environmental factors, and coronary stents that can present in the same way as non-allergy-induced acute coronary syndrome. Here within, we present a unique case of dual presentation of Kounis syndrome and prolonged QTc in a young patient after a single dose of Domperidone and Lansoprazole.


Author(s):  
Narcisa Muresu ◽  
Giovanni Sotgiu ◽  
Bianca Maria Are ◽  
Andrea Cossu ◽  
Clementina Cocuzza ◽  
...  

Enteric fever is a foodborne infectious disease caused by Salmonella enterica serotypes Typhi and Paratyphi A, B and C. The high incidence in low income countries can increase the risk of disease in travelers coming from high income countries. Pre-travel health advice on hygiene and sanitation practices and vaccines can significantly reduce the risk of acquiring infections. Although the majority of the cases are self-limiting, life-threatening complications can occur. Delayed diagnosis and cases of infections caused by multi-drug resistant strains can complicate the clinical management and affect the prognosis. More international efforts are needed to reduce the burden of disease in low income countries, indirectly reducing the risk of travelers in endemic settings. Surveillance activities can help monitor the epidemiology of cases caused by drug-susceptible and resistant strains.


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