Cardiovascular and respiratory reactions
Cardiovascular and respiratory adverse reactions were reported in 33 studies. Of these, two were randomized controlled trials 33, 59, 30 were cohort studies 7, 18, 23, 25– 27, 36, 39– 41, 51, 54, 61, 65, 66, 68, 73, 74, 80, 85– 87, 90, 100– 102, 104, 115, 117, and one was a preliminary report 91. Except for one study 66, all studies reporting cardiovascular and respiratory reactions administered DMSO intravenously ( Table 3 and Table 4).
Table 3.  Cardiovascular and respiratory adverse reactions observed per number of patients.
Adverse reaction  Studies  Total patients, n  Patients with adverse reactions, n (%)  (min%–max%) †
Cardiac
   Hypotension ‡  [ 7, 18, 23, 33, 71, 73, 87, 104, 115]  2752  115 (4)  (1–14) [ 18, 71] - [ 87]
   Hypertension §  [ 7, 18, 23, 33, 41, 54, 61, 73, 85, 87, 102]  2998  385 (13)  (2–95) [ 85] - [ 61]
   Bradycardia (mild and severe) ‡  [ 23, 36, 54, 61, 65, 85, 90, 91, 115, 117]  882  94 (11)  (0–49) [ 36] - [ 61]
   Decrease in heart rate ‡  [ 41, 54, 61, 80]  193  152 (79)  (11–94) [ 80] - [ 41]
   Tachycardia ‡  [ 23, 27, 36]  565  13 (2)  (0–6) [ 36] - [ 23]
   Ventricular extrasystoles ‡  [ 73]  22  11 (50)
   Cardiac event, unspecified ‡  [ 26, 86]  165  18 (11)  (5–12) [ 26] - [ 86]
   Asystole ¶  [ 91, 100]  45  3 (7)  (3–20) [ 100] - [ 91]
   Left cardiac insufficiency  [ 85]  194  1 (1)
   Chest discomfort/tightness ‡  [ 18, 27, 54, 73, 87, 91, 115]  901  22 (2)  (1–10) [ 27] - [ 54]
Respiratory
   Unspecified respiratory  symptoms ‡  [ 26, 86]  165  43 (26)  (21–62) [ 86] - [ 26]
   Dyspnea d  [ 18, 27, 54, 66, 85]  2748  26 (1)  (0–10) [ 66] - [ 54]
   Cough  [ 85, 101]  373  52 (14)  (5–22) [ 101] [ 85]
   Lung edema ‡  [ 59, 85]  241  3 (1)  (1–2) [ 85] - [ 59]
†Incidences of the adverse reactions have been calculated for all the individual studies. (min%–max%) are the lowest and highest observed incidence of an adverse reaction.
‡ DMSO was administered intravenously in all studies.
§ DMSO was administered intravenously in all studies. Horacek et al. [ 102] measured 42 patients with an increase in systolic blood pressure, and 31 patients with an increase in diastolic blood pressure. This was counted as 73 cases of hypertension.
¶ In both studies, asystole occurred because of DMSO effect on the trigeminal nerve and activation of the trigeminal cardiac reflex. d) in one study DMSO was administered transdermally
Table 4.  Cardiovascular and respiratory adverse reactions observed per number of treatments.
Adverse reaction  Studies  Total number of treatments  Adverse reactions observed, n (%)  (min%–max%) †
Cardiac
   Hypotension ‡  [ 40, 51, 68]  323  10 (3)  (2–14) [ 68] - [ 40]
   Hypertension ‡  [ 25, 51, 68]  425  60 (14)  (3–21) [ 25] - [ 68]
   Bradycardia (mild and severe) ‡  [ 51]  54  4 (7)
   Decrease in heartrate ‡  [ 39]  32  30 (94)
   Tachycardia ‡  [ 51]  54  4 (7)
   Cardiac event, unspecified ‡  [ 74]  1269  35 (3)
   Chest discomfort/tightness ‡  [ 25, 68, 74]  1640  83 (5)  (0–6) [ 68] - [ 74]
Respiratory
   Dyspnea  [ 25, 68]  371  3 (1)  (0–2) [ 68] - [ 25]
   Shortness of breath ‡  [ 74]  1269  40 (3)
†Incidences of the adverse reactions have been calculated for all the individual studies. (%, min-max) are the lowest and highest observed incidence of an adverse reaction observed in the group of studies included.
‡ DMSO was administered intravenously. Bradycardia was defined as a heart rate less than 60 beats per minute 41, 61 and was often transient 23, 61, 90, 115, but cases where atropine was needed are described 49, 96. A lowered heart rate not enough to be considered bradycardia was observed in four studies 39, 41, 54, 61.
In some studies, hypertension did not require intervention 61, 102, but cases where medication was needed to control the hypertension, or where treatment was stopped due to hypertension, are described 41, 54, 85. Hypotension was also described as transient most of the time 18, 23, 68, 87, 104, with some cases needing intervention 40, 51, 54.
One study reported 11 cases of transient extrasystoles in 22 patients receiving cryopreserved autologous blood stem cells, monitored with Holter during infusion 73. There were two studies reporting cases of asystole during embolization of dural arteriovenous fistulas with a substance called Onyx, a non-adhesive liquid embolic agent dissolved in DMSO 91, 100.
Dyspnea was reported in seven studies 18, 25, 27, 54, 66, 68, 85. A single study reported eight patients with transient shock after stem cell transfusion 51. Some of these patients developed loss of consciousness and cyanosis but recovered promptly and had no need for additional therapy, whereas the rest of the patients developed severe hypotension or transient dyspnea, which was described as the reason for the transient shock. Further description of the condition was not provided.
Several of the studies found a correlation between the dose of DMSO used and the incidence of cardiovascular adverse reactions 41, 67, 71, 75, 78, 85, 86, 93, 101, 115.