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Dimethylsulfoxide
General information
Dimethylsulfoxide is an agent with a wide spectrum of pharmacological effects, including membrane penetration, anti-inflammatory effects, local analgesia, and weak bacteriostasis. The principal use of dimethylsulfoxide is as a vehicle for other drugs, thereby enhancing the effect of the drug, and aiding penetration of other drugs into the skin. Dimethylsulfoxide has been given orally, intravenously, or topically for a wide range of indications. It is also given by bladder instillation in the symptomatic relief of interstitial cystitis, and is used as a cryoprotectant for various human tissues.
In preparation for bone marrow transplantation, autologous hemopoietic stem cells are normally frozen in liquid nitrogen after harvesting. However, a cryoprotective agent is required, and dimethylsulfoxide is normally used. During and immediately after stem cell infusion, many adverse effects, which may be severe or life-threatening, have been reported. They include hypotension and hypertension, anaphylactic reactions, and cardiac and respiratory failure, all possibly due to dimethylsulfoxide, hemolysis induced by cryopreservation and thawing, and fluid overload.
In a retrospective study, 30 children were reviewed after bone marrow or peripheral autologous hemopoietic transplantation [ ]. At the time of infusion, hydrocortisone, chlorphenamine, and hyperhydration were administered to all patients, and furosemide and tropisetron to most. Vital signs and symptoms were monitored for 6 hours after the infusion. Thawing was performed rapidly at the bedside in a 42°C water-bath, and the cells were infused through a central venous catheter at 10 ml/minute. All 32 procedures were well tolerated; there were infusion-related adverse effects in 15 of 32 infusions, but none required specific therapy. There was mild bradycardia in nine patients, one reported abdominal pain, two reported headache, and three had hemoglobinuria. The authors concluded that a single-step cryopreservation technique aimed at limiting the total amount of dimethylsulfoxide is effective in avoiding most toxicity while not compromising post-thawing viability.
The efficacy and safety of dimethylsulfoxide are still relatively unclear; few studies have been performed in such a way as to permit reliable conclusions. Dimethylsulfoxide penetrates quickly through the tissues, and there are no great differences between its effects after different routes of administration. Adverse reactions are common, but can be avoided in large part by using more dilute solutions [ ]. Although the systemic toxicity of dimethylsulfoxide is considered to be low, it can potentiate the effect of simultaneously administered drugs. Combinations of dimethylsulfoxide with other toxic agents probably constitute its greatest toxic potential [ ].
Organs and systems
Nervous system
The infusion of dimethylsulfoxide-cryopreserved autologous peripheral blood stem cells has been associated with a number of infusion-related adverse effects [ ]. Severe reversible encephalopathy was experienced by two patients after infusion of peripheral blood stem cells cryopreserved in 10% dimethylsulfoxide. In one patient, reduction of the plasma dimethylsulfoxide concentration by plasmapheresis resulted in marked improvement in encephalopathy [ ]. The presence of renal insufficiency may have predisposed to the development of neurological toxicity by delaying the excretion of dimethylsulfoxide and its metabolites. Other cases of dimethylsulfoxide-induced encephalopathy have been described [ ].
Toxicity related to the infusion of dimethylsulfoxide-cryopreserved peripheral blood stem cells mainly comprises cardiovascular events. Autologous stem cell transplantation complicated by cerebral infarction and myocardial damage has been reported [ ] and it has been postulated that dimethylsulfoxide may have been responsible.
Of 51 patients who received dimethylsulfoxide-preserved peripheral blood stem cells only one had neurotoxicity in the form of a generalized tonic seizure after the infusion [ ]. However, there was no neurotoxicity in eight patients with pre-existing neurological disease nor in patients who received particularly large volumes of dimethylsulfoxide. In all patients, there were mild non-neurological adverse effects.
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A 49-year-old man who received two infusions of dimethylsulfoxide (DMSO) cryopreserved autologous peripheral blood progenitor cells after myeloablative chemotherapy for a relapsing lymphoma had a tonic-clonic seizure over a few minutes after the start of each infusion and developed a profound and sustained but reversible encephalopathy with coma after the second infusion [ ]. His neurological condition correlated with the electrophysiological findings (electroencephalography and multimodality evoked potentials) and to a lesser extent with MRI abnormalities.
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A 50-year-old woman with nodular-sclerosing Hodgkin's disease received stem cells cryopreserved in 10% dimethylsulfoxide, which were infused after high-dose conditioning, with carmustine, etoposide, cytarabine, and melphalan and premedication with diphenhydramine 50 mg and hydrocortisone 200 mg [ ]. After infusion of the second bag, she became pale, lost consciousness, and developed mydriasis, trismus, and respiratory arrest. The stem cell infusion was immediately stopped. She was given phenytoin 15 mg/kg and assisted ventilation and recovered consciousness in less than an hour. She was given intravenous phenytoin 4.5 mg/kg for 5 days and then switched to oral therapy. Later the remaining cryopreserved stem cells were reinfused and there were no adverse effects. A brain CT scan was normal but an electroencephalogram showed diffuse abnormalities in electrical activity with irregular slow-wave paroxysms. A brain MRI scan showed a small punctate area of hyperintensity in the right middle frontal lobe of unclear significance.
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