•
Diagnostic Radiology
Bradycardia and Hypotension following Use of Intravenous Contrast Media 1 Robert J. Stanley, M.D., and Richard C. Pfister, M.D. Eight patients had unusual reactions, including hypotension and bradycardia, to intravenous contrast media. These reactions appear to be vagal- or acetylcholine-mediated. Atropine treatment produced prompt reversal in several of the cases, and is felt to be the drug of choice for this particular type of idiosyncratic reaction. INDEX TERMS: Contrast media, effects • (Heart, adverse reactions to contrast medium, 5 [ 1] .448) • Heart, effect of drugs on • Nerves, vagus. (Vascular systems, adverse reactions to contrast medium, 9.448) Radiology 121:5-7, October 1976
•
•
A N ATYPICAL "ANAPHYLACTOID"
REACTION, as one type of adverse reaction to water soluble contrast media, may occasionally be encountered during intravenous urography or cholangiography. This reaction consists of hypotension associated with bradycardia or a lack of the tachycardia which is the usual response to a sudden fall in blood pressure. The cardiovascular changes may be accompanied by intestinal cramping, salivation, sweating, and unconsciousness, with spontaneous urination and defecation. Restlessness and apprehension may precede all of the other signs and symptoms. The combination of hypotension and bradycardia suggests a vago-vagal response to some stimulus. All of the changes, including the cardiovascular ones, could be described as examples of the muscarinic action of acetylcholine; these signs and symptoms very closely resemble those of acute anticholinesterase toxicity (9). In several of the cases we will describe, intravenous or intramuscular atropine treatment produced a prompt reversal of the reaction, further supporting the impression that the reactions were vagal- or acetylcholine-mediated. While this type of reaction in a young healthy patient may be transient and inconsequential, the risk of myocardial ischemia and/or infarction in the older patient requires that the nature of the reaction be recognized quickly and that specific therapy be initiated.
CASE II: A 75-year-Old man with Hodgkin's disease underwent infusion urography for evaluation of sepsis of unknown origin. Eight minutes following the administration of 250 ml of 25% Hypaque (diatrizoate sodium) he became restless and experienced shortness of breath. His blood pressure fell from 120/70 to a systolic of 30, and his pulse went from 92 to 30 with a regular rhythm. Ausculation indicated that the lungs were clear. Treatment with intravenous fluids, glucocorticoids, and a vasopressor (epinephrine) over 30 min. slowly elevated the blood pressure to 90/60 and the pulse to 62. Over the next hour a gradual return to baseline blood pressure and heart rate evolved and stabilized. No apparent sequelae to the contrast media reaction were evident.
1-\
CASE III: A 64-year-old woman with a blood pressure of 115/84 and a pulse of 82 underwent urography 9 days following cystectomy and ileal conduit diversion for carcinoma of the bladder. She became diaphoretic approximately 15 minutes following the administration of 300 ml of Conray-30. Her blood pressure was 60/30, and her heart rate 54. Intravenous fluids, steriods and antihistamine therapy had no effect; the blood pressure continued to fall to 40/0 and a continuous vasopressor drip was required over the next 20 hours to maintain an adequate blood pressure. The initial electrocardiogram revealed only sinus bradycardia, but 24 hours later indicated an acute myocardial infarction, and further acute oliguric renal failure developed. Follow ing a prolonged recovery period she was discharged in good health, and has subsequently undergone intravenous urography on two occasions without adverse reaction or pretreatment for same. CASE IV: A 40-year-old white man complained of tightness and pain across the back. His admission blood pressure was 130/100, and his pulse was 80/min. An excretory urogram was obtained to exclude ureteral lithiasis as a cause of the patient's pain. Ten minutes after the. intravenous administration of 75 ml of Conray-400, the patient was noted to be restless and diaphoretic; blood pressure was 70/40 mm Hg and pulse 55/min. Intravenous fluids were started, oxygen was given by mask, and 0.5 mg of atropine was injected intravenously. The patient improved remarkably over the next few minutes. Within 10 minutes his blood pressure was 120/80 and his pulse 80/min. There were no adverse sequelae, and his electrocardiogram was normal.
CASE REPORTS CASE I: A 58-year-old man complained of left lower quadrant and periumbical pain. His admission blood pressure was 120/80 and his pulse was 70. His diagnostic evaluation included an excretory urogram. Three minutes after the intravenous injection of 30 ml of Conray-60 (iothalamic acid), a flushed appearance and marked apprehension developed. His blood pressure had dropped to 70/40, and his pulse was 45 and regular. He became unconscious, spontaneously voided and defecated, and then convulsed. For approximately 30 seconds there was no respiration and no detectable pulse or blood pressure. Spontaneous respirations then returned. His treatment included epinephrine, glucocorticoids and an antihistamine. No atropine was given. Within 45 minutes the patient's blood pressure and pulse had returned to. normal. Subsequently no adverse sequelae were recognized. The patient's electrocardiogram remained normal.
CASE V: A 19-year-old man being evaluated for the possibility ofrenal stones received 50 ml of Conray-60 intravenously. Within several minutes he became restless and apprehensive. Bradycardia of SO/min. and a systolic pressure below 80 were noted. The patient was immediately given 0.5 mg of atropine intravenously; over the next 10 minutes his pulse and blood pressure returned to normal. After an appropriate period of observation it was determined that the patient could leave the department without further treatment.
1 From the Departments of Radiology of Mallinckrodt Institute of Radiology, St. Louis, Mo. (R.J.S.) and Massachusetts General Hospital, Boston, Mass. (R.C.P.), and the Subcommittee on Treatment of Adverse Contrast Media Reactions of the Committee on Contrast Media of the International Society of Radiology, Dr. W. H. Shehadi, Chairman. Presented at the Society of Uroradiology, Chicago, III., 29 Nov., 1975. ss
5
ROBERT J. STANLEY AND RICHARD C. PFISTER
6
CASE VI: A 74-year-old white woman was admitted forevaluation of abdominal pain and microscopic hematuria. The patient's history included cholecystectomy. Her admission blood pressure was 154/80, her pulse 80/min. An intravenous cholangiogram was requested, and an infusion of 40 mlof Cholografin (N-methyl glucamine iodipamide) in 250 ml of 5% dextrose and water was started. Within 20 minutes, after 150 ml of the solution had been infused, the patient became restless and apprehensive, and complained of abdominal cramping, stating that she felt as if she were fainting. Her blood pressure had dropped to 100/60 and her pulse to 60/min. with a regular rhythm. Because this did not appear tobe asevere reaction, 0.6 mg ofatropine was administered intramuscularly and the rate of infusion was slowed but not discontinued. Within 15 minutes the patient's blood pressure had risen to 130/80, and her pulse to 64/min.; she stated that she was feeling better. Within 30 minutes her blood pressure had returned to the prestudy level of 160/80, and her pulse to 80/min. The patient at that point felt "back to normal." The study was completed, and the patient underwent normal postcholecystectomy cholangiography. No subsequent problems were recognized during the patient's hospitalization. CASE VII: An 80-year-old woman was hospitalized because of a urinary tract infection associated with a staghorn renal calculus. Her blood pressure was 110170 and her pulse, 80. After receiving a 100-ml
Renografin-30 (N-methyl glucamine diatrizoate) infusion she became apprehensive and clammy. Hypotension (72/34) and bradycardia (42 with occasional premature ventricular contraction) were found and she was treated with 0.75 mg of atropine intravenously and fluids. Within 3 minutes the heart rate was 75 (with one premature ventricular contraction) and her blood pressure was 94160. Rapid further return to normal pulse and blood pressure permitted completion ofthe urographic study. CASE VIII: A 22-year-old woman was admitted foran evaluation of hypertension. Her admission blood pressure was 145/95 and her pulse rate 82/min. Within two minutes after the intravenous administration ofa50-ml bolus ofRenografin-60 she became nauseated and vomited. Generalized erythema and restlessness accompanied adrop inblood pressure to 5010 and a slowing ofthe heart rate to20/min. Intravenous fluids and 0.8 mg of atropine were given intravenously. Within three minutes the heart rate had returned to normal range, but the blood pressure remained depressed. Volume expanders were given, and after a 30-min. period of hypotension the blood pressure gradually returned to a prestudy level. No adverse sequelae were evident.
DISCUSSION
In shock (a systolic pressure of 80 mm Hg or less), a rapid weak pulse is characteristic. A rapid pulse usually appears before the decline in blood pressure, and may be of diagnostic value. Sinus bradycardia denotes that the cardiac impulse arises normally in the sino-atrial node, but that the cardiac rate is less than SO/min. This must be differentiated from a slow nodal rhythm and from heart block; the electrocardiogram is usually necessary for a definite diagnosis. The mechanism is usually an increase in vagal tone, or sometimes a diminution of sympathetic tone. Dyspnea, palpatation, dizziness, faintness, or syncope may be associated with slow cardiac rates. The association of moderate to severe hypotension with bradycardia suggests that they are mediated by the vagus nerve, either by way of the carotid sinus or, more likely, due to stimulation of the vagal centers in the brain stem. Vagal stimulation may result in: (a) Vasodilatation with a sharp fall in blood pressure due to reflex peripheral vasodilatation, particularly in muscles (postarteriolar loss of
October 1976
tone involving capillaries and venules), with pooling of blood in small vessels and an acute deficiency in venous return and cardiac output; and (b) Cardiac slowing, cardiac standstill, or heart block with or without ventricular standstill, since acetylcholine increases membrane permeability to potassiumand slows or arrests the rhythmicity of the sino-atrial node. As a result, cerebral ischemia and loss of consciousness (syncope) with or without convulsions may occur, as may myocardial hypoxia and infarction (1).
A vasovagal reaction is distinguished from a vagovagal response in that the former is due exclusively to a sharp' decline in blood pressure secondaryto a loss of vasomotor tone (resulting from a variety of factors), whereas cardiac slowing or standstill is an important feature of the vagovagal reflex. Reflex tachycardia is usually present in vasovagal reactions. Bradycardia, if present, is minimal and insignificant. Treatment of a conventional adverse reaction (hypotension and tachycardia) to contrast media is directed
toward restoration of adequate blood pressure and cardiac output by means of (a) plasma expanders or solutions of sodium chloride with or without potassium or alkalis, or both; or (b) the use of vasopressor agents with or without glucocorticoids. The less frequent occurrence of bradycardia and hypotension, and their elimination by atropine (TABLE I), suggests that at least these manifestations are mediated by way of the vagus nerve (vagovagal reaction). While the sympathomimetic drugs are commonly used, they would appear to be of little value in most cases of vagal-mediated syncope, due to vasodilatation and slow heart rate. Lasser and Lang (4-6) reported on the inhibition of acetylcholinesterase by organic contrast media, and commented on the similarity between reactions to contrast media and acute anticholinesterase poisoning. The reversibility of the latter with atropine is well recognized (8, 9). Viner and Rhamy (10) reported on 3 patients in whom prolonged hypotension developed (14-24 hr.) without tachycardia following intravenous contrast medium (2 patients) and penicillin. None was treated with atropine, and all were resistant to the pressor effect of epinephrine. While the cause of the prolongedand resistanthypotension was never explained, the authors suggested that the cholinesterase-inhibiting properties of the contrast agents could have played a role. Atropine is commonly employed as premedication for many angiographic procedures to reduce vasovagal and vagovagal reactions. It appears to diminish the incidence and severity of reflex hypotension and bradycardia noted in cerebral angiography. Both Grietz and Tornell (3) and Lundervold and Engeset (7) discussed the bradycardial reactions, but were unable to explain their relationship to the contrast agent. It is unclear what the relationship is between the bradycardia seen in cerebral angiography and the reaction types to intravenous contrast media described here. Nevertheless, the efficacy of atropine as a premedication in the management of bradycardia and hypotension following cerebral angiography is established. The value of atropine in the treatment of the same types of reaction following the use of intravenous contrast me-
UNUSUAL REACTIONS TO INTRAVENOUS CONTRAST MEDIA
Vol. 121
dium is strongly suggested from our limited experience. CASE VIII, however, illustrates some of the problems that can be encountered in the management of this reaction, even with use of atropine. The heart rate of 20/min., never recorded by electrocardiogram, was either a profound sinus bradycardia, a nodal or other supraventricular bradycardia, or an idioventricular rhythm. It responded immediately to intravenous atropine, converting to a normal sinus rhythm within minutes. If the drop in blood pressure was solely related to a diminished cardiac output secondary to the bradycardia, it should have returned to normal coincident with the resumption of the normal sinus rhythm. The persistence of the hypotension suggests several alternative possibilities: (a) Other non-vagal causal factors produced peripheral vasodilatation; or (b) The response of a vagovagal reaction to atropine is dose dependent, with cardiac rate being most sensitive and the peripheral resistance less sensitive. If this is true, doses in the range of 1 to 2 mg would be more appropriate; there is some pharmacologic evidence to support this (2).
Department of Radiology Mallinckrodt Institute of Radiology 510 S. Kingshighway St. Louis, Mo. 63110
REFERENCES 1. Friedenberg CK: Diseases of the Heart. Philadelphia, Saunders, 3d ed, 1966, pp 462-469 2. Goodman LS, Gilman S: The Pharmacological Basis of Therapeutics. London, Macmillan, 4th ed, 1970, pp 530-531 3. Greitz T, Tornel! G: Bradycardial reactions during cerebral angiography. Acta Radial 270:75-86, 1967 4. Lasser EC, Lang JH: Contrast-Protein interactions. Invest Radiol 5:446-451, Nov 1970 5. LasserEC, Lang JH: Inhibitionof acetylcholinesterase by some organic contrast media. Invest RadioI1:237-242, May 1966 6. Lasser EC, Walters AJ, Lang WH: An experimental basis for histamine release in contrast material reactions. Radiology 110:49-59, Jan 1974 7. Lundervold A, Engeset A: Recordings of EEG, ECG, EMGand intraarterial blood pressure during cerebral angiography. Acta Radiol 270:198-207, 1967 8. Modell W: Drugs of Choice. St. Louis, Mosby, 1974-75, pp 299-302 9. Sim VM: Diagnosis and therapy for anticholinesterase poisoning. JAMA 192:143-144, May 1965 10. Viner NA, RhamyRK: Anaphylaxismanifestedby hypotension alone. J UroI113:108-110, Jan 1975
The management of most severe reactions to intravenous water-soluble contrast agents involves the use of epinephrine, aminophyllin, and other pharmacologic agents (glucocorticoids, antihistamines)as complications develop, as well as supportive measures such as oxygen, intravenous fluids, assisted ventilation, external cardiac massage, and defibrillation. Our experience indicates that one type of reaction, infrequent in occurrence, with the combined
Case Dose No. Method
Contrast Medium
Time Onset Reaction (min)
30-ml Bolus
Conray60
3
250-ml Infusion
Hypaque25
8
300-ml lnfusion
Conray
4
75-ml Bolus
Conray400
10
5
50-ml Bolus
Conray60
6
150-ml Infusion
Cholegrafin
7
100-ml Infusion
Renografin-30
4
8
50-ml Bolus
Renografin-60
2
1
2
3
15
Progress of Cases Hrt. Rate
Bid. Press. Symptom Sequence
Initial
---Reaction
Apprehension Flushing Unconscious Convulsions Apnea
120/80
70
70/40
45
Restlessness Dyspnea Unconscious
120/70
92
30/0
30
Restlessness
115/84
82
Diaphoresis Unconscious
40/0
54
Restlessness Diaphoresis
130/100 80
3
Restlessness Apprehension
125/85
20
Restlessness Apprehension Abdominal Cramping
..-
._-------_.~_._-----_
70/40
55
80/... 154/80
50 80
100/60
60
Apprehension Clammy
110/70
80
72/34
42
Vomiting Erythema Restlessness
145/95
82 ---
50/0
Diagnostic Radiology
signs of bradycardia and hypotension, should be treated with intramuscular or preferably intravenous atropine in the range of 0.5 to 2.0 mg as the initial drug of choice, followed by careful monitoring of the patient's response. Prompt recognition and treatment may avert further complications and the use of inappropriate or nonspecific drugs.
SUMMARY
Table I:
7
20
Treatment
Time to Return Normal BP & Heart Rate
Comments
Epinephrine Steroids Antihistamine
45 min.
No sequelae
Saline Steroids Epinephrine
60 min.
No sequelae
Mannitol Steroids Antihistamine Epinephrine Norepinephrine Drip
20 hrs.
Resistant hypotension Acute myocardial infarction Acute renal failure Subsequent urography
Saline 0.5 mg atropine IV
10 min.
No sequelae
0.5 mg atropine IV
10 min.
No sequelae
0.6 mg atropine 1M
30 min.
No sequelae
8 min.
No sequelae
5% D/W 0.75 mg atropine IV Ringer's Albumisol Saline 0.8 mg atropine IV
--._----
3 min. Heart rate 30 min. B.P.
No sequelae
--_._'-
--~-~---_._._._---~---
Diagnostic Radiology
Bradycardia and Hypotension following Use of Intravenous Contrast Media 1 Robert J. Stanley, M.D., and Richard C. Pfister, M.D. Eight patients had unusual reactions, including hypotension and bradycardia, to intravenous contrast media. These reactions appear to be vagal- or acetylcholine-mediated. Atropine treatment produced prompt reversal in several of the cases, and is felt to be the drug of choice for this particular type of idiosyncratic reaction. INDEX TERMS: Contrast media, effects • (Heart, adverse reactions to contrast medium, 5 [ 1] .448) • Heart, effect of drugs on • Nerves, vagus. (Vascular systems, adverse reactions to contrast medium, 9.448) Radiology 121:5-7, October 1976
•
•
A N ATYPICAL "ANAPHYLACTOID"
REACTION, as one type of adverse reaction to water soluble contrast media, may occasionally be encountered during intravenous urography or cholangiography. This reaction consists of hypotension associated with bradycardia or a lack of the tachycardia which is the usual response to a sudden fall in blood pressure. The cardiovascular changes may be accompanied by intestinal cramping, salivation, sweating, and unconsciousness, with spontaneous urination and defecation. Restlessness and apprehension may precede all of the other signs and symptoms. The combination of hypotension and bradycardia suggests a vago-vagal response to some stimulus. All of the changes, including the cardiovascular ones, could be described as examples of the muscarinic action of acetylcholine; these signs and symptoms very closely resemble those of acute anticholinesterase toxicity (9). In several of the cases we will describe, intravenous or intramuscular atropine treatment produced a prompt reversal of the reaction, further supporting the impression that the reactions were vagal- or acetylcholine-mediated. While this type of reaction in a young healthy patient may be transient and inconsequential, the risk of myocardial ischemia and/or infarction in the older patient requires that the nature of the reaction be recognized quickly and that specific therapy be initiated.
CASE II: A 75-year-Old man with Hodgkin's disease underwent infusion urography for evaluation of sepsis of unknown origin. Eight minutes following the administration of 250 ml of 25% Hypaque (diatrizoate sodium) he became restless and experienced shortness of breath. His blood pressure fell from 120/70 to a systolic of 30, and his pulse went from 92 to 30 with a regular rhythm. Ausculation indicated that the lungs were clear. Treatment with intravenous fluids, glucocorticoids, and a vasopressor (epinephrine) over 30 min. slowly elevated the blood pressure to 90/60 and the pulse to 62. Over the next hour a gradual return to baseline blood pressure and heart rate evolved and stabilized. No apparent sequelae to the contrast media reaction were evident.
1-\
CASE III: A 64-year-old woman with a blood pressure of 115/84 and a pulse of 82 underwent urography 9 days following cystectomy and ileal conduit diversion for carcinoma of the bladder. She became diaphoretic approximately 15 minutes following the administration of 300 ml of Conray-30. Her blood pressure was 60/30, and her heart rate 54. Intravenous fluids, steriods and antihistamine therapy had no effect; the blood pressure continued to fall to 40/0 and a continuous vasopressor drip was required over the next 20 hours to maintain an adequate blood pressure. The initial electrocardiogram revealed only sinus bradycardia, but 24 hours later indicated an acute myocardial infarction, and further acute oliguric renal failure developed. Follow ing a prolonged recovery period she was discharged in good health, and has subsequently undergone intravenous urography on two occasions without adverse reaction or pretreatment for same. CASE IV: A 40-year-old white man complained of tightness and pain across the back. His admission blood pressure was 130/100, and his pulse was 80/min. An excretory urogram was obtained to exclude ureteral lithiasis as a cause of the patient's pain. Ten minutes after the. intravenous administration of 75 ml of Conray-400, the patient was noted to be restless and diaphoretic; blood pressure was 70/40 mm Hg and pulse 55/min. Intravenous fluids were started, oxygen was given by mask, and 0.5 mg of atropine was injected intravenously. The patient improved remarkably over the next few minutes. Within 10 minutes his blood pressure was 120/80 and his pulse 80/min. There were no adverse sequelae, and his electrocardiogram was normal.
CASE REPORTS CASE I: A 58-year-old man complained of left lower quadrant and periumbical pain. His admission blood pressure was 120/80 and his pulse was 70. His diagnostic evaluation included an excretory urogram. Three minutes after the intravenous injection of 30 ml of Conray-60 (iothalamic acid), a flushed appearance and marked apprehension developed. His blood pressure had dropped to 70/40, and his pulse was 45 and regular. He became unconscious, spontaneously voided and defecated, and then convulsed. For approximately 30 seconds there was no respiration and no detectable pulse or blood pressure. Spontaneous respirations then returned. His treatment included epinephrine, glucocorticoids and an antihistamine. No atropine was given. Within 45 minutes the patient's blood pressure and pulse had returned to. normal. Subsequently no adverse sequelae were recognized. The patient's electrocardiogram remained normal.
CASE V: A 19-year-old man being evaluated for the possibility ofrenal stones received 50 ml of Conray-60 intravenously. Within several minutes he became restless and apprehensive. Bradycardia of SO/min. and a systolic pressure below 80 were noted. The patient was immediately given 0.5 mg of atropine intravenously; over the next 10 minutes his pulse and blood pressure returned to normal. After an appropriate period of observation it was determined that the patient could leave the department without further treatment.
1 From the Departments of Radiology of Mallinckrodt Institute of Radiology, St. Louis, Mo. (R.J.S.) and Massachusetts General Hospital, Boston, Mass. (R.C.P.), and the Subcommittee on Treatment of Adverse Contrast Media Reactions of the Committee on Contrast Media of the International Society of Radiology, Dr. W. H. Shehadi, Chairman. Presented at the Society of Uroradiology, Chicago, III., 29 Nov., 1975. ss
5
ROBERT J. STANLEY AND RICHARD C. PFISTER
6
CASE VI: A 74-year-old white woman was admitted forevaluation of abdominal pain and microscopic hematuria. The patient's history included cholecystectomy. Her admission blood pressure was 154/80, her pulse 80/min. An intravenous cholangiogram was requested, and an infusion of 40 mlof Cholografin (N-methyl glucamine iodipamide) in 250 ml of 5% dextrose and water was started. Within 20 minutes, after 150 ml of the solution had been infused, the patient became restless and apprehensive, and complained of abdominal cramping, stating that she felt as if she were fainting. Her blood pressure had dropped to 100/60 and her pulse to 60/min. with a regular rhythm. Because this did not appear tobe asevere reaction, 0.6 mg ofatropine was administered intramuscularly and the rate of infusion was slowed but not discontinued. Within 15 minutes the patient's blood pressure had risen to 130/80, and her pulse to 64/min.; she stated that she was feeling better. Within 30 minutes her blood pressure had returned to the prestudy level of 160/80, and her pulse to 80/min. The patient at that point felt "back to normal." The study was completed, and the patient underwent normal postcholecystectomy cholangiography. No subsequent problems were recognized during the patient's hospitalization. CASE VII: An 80-year-old woman was hospitalized because of a urinary tract infection associated with a staghorn renal calculus. Her blood pressure was 110170 and her pulse, 80. After receiving a 100-ml
Renografin-30 (N-methyl glucamine diatrizoate) infusion she became apprehensive and clammy. Hypotension (72/34) and bradycardia (42 with occasional premature ventricular contraction) were found and she was treated with 0.75 mg of atropine intravenously and fluids. Within 3 minutes the heart rate was 75 (with one premature ventricular contraction) and her blood pressure was 94160. Rapid further return to normal pulse and blood pressure permitted completion ofthe urographic study. CASE VIII: A 22-year-old woman was admitted foran evaluation of hypertension. Her admission blood pressure was 145/95 and her pulse rate 82/min. Within two minutes after the intravenous administration ofa50-ml bolus ofRenografin-60 she became nauseated and vomited. Generalized erythema and restlessness accompanied adrop inblood pressure to 5010 and a slowing ofthe heart rate to20/min. Intravenous fluids and 0.8 mg of atropine were given intravenously. Within three minutes the heart rate had returned to normal range, but the blood pressure remained depressed. Volume expanders were given, and after a 30-min. period of hypotension the blood pressure gradually returned to a prestudy level. No adverse sequelae were evident.
DISCUSSION
In shock (a systolic pressure of 80 mm Hg or less), a rapid weak pulse is characteristic. A rapid pulse usually appears before the decline in blood pressure, and may be of diagnostic value. Sinus bradycardia denotes that the cardiac impulse arises normally in the sino-atrial node, but that the cardiac rate is less than SO/min. This must be differentiated from a slow nodal rhythm and from heart block; the electrocardiogram is usually necessary for a definite diagnosis. The mechanism is usually an increase in vagal tone, or sometimes a diminution of sympathetic tone. Dyspnea, palpatation, dizziness, faintness, or syncope may be associated with slow cardiac rates. The association of moderate to severe hypotension with bradycardia suggests that they are mediated by the vagus nerve, either by way of the carotid sinus or, more likely, due to stimulation of the vagal centers in the brain stem. Vagal stimulation may result in: (a) Vasodilatation with a sharp fall in blood pressure due to reflex peripheral vasodilatation, particularly in muscles (postarteriolar loss of
October 1976
tone involving capillaries and venules), with pooling of blood in small vessels and an acute deficiency in venous return and cardiac output; and (b) Cardiac slowing, cardiac standstill, or heart block with or without ventricular standstill, since acetylcholine increases membrane permeability to potassiumand slows or arrests the rhythmicity of the sino-atrial node. As a result, cerebral ischemia and loss of consciousness (syncope) with or without convulsions may occur, as may myocardial hypoxia and infarction (1).
A vasovagal reaction is distinguished from a vagovagal response in that the former is due exclusively to a sharp' decline in blood pressure secondaryto a loss of vasomotor tone (resulting from a variety of factors), whereas cardiac slowing or standstill is an important feature of the vagovagal reflex. Reflex tachycardia is usually present in vasovagal reactions. Bradycardia, if present, is minimal and insignificant. Treatment of a conventional adverse reaction (hypotension and tachycardia) to contrast media is directed
toward restoration of adequate blood pressure and cardiac output by means of (a) plasma expanders or solutions of sodium chloride with or without potassium or alkalis, or both; or (b) the use of vasopressor agents with or without glucocorticoids. The less frequent occurrence of bradycardia and hypotension, and their elimination by atropine (TABLE I), suggests that at least these manifestations are mediated by way of the vagus nerve (vagovagal reaction). While the sympathomimetic drugs are commonly used, they would appear to be of little value in most cases of vagal-mediated syncope, due to vasodilatation and slow heart rate. Lasser and Lang (4-6) reported on the inhibition of acetylcholinesterase by organic contrast media, and commented on the similarity between reactions to contrast media and acute anticholinesterase poisoning. The reversibility of the latter with atropine is well recognized (8, 9). Viner and Rhamy (10) reported on 3 patients in whom prolonged hypotension developed (14-24 hr.) without tachycardia following intravenous contrast medium (2 patients) and penicillin. None was treated with atropine, and all were resistant to the pressor effect of epinephrine. While the cause of the prolongedand resistanthypotension was never explained, the authors suggested that the cholinesterase-inhibiting properties of the contrast agents could have played a role. Atropine is commonly employed as premedication for many angiographic procedures to reduce vasovagal and vagovagal reactions. It appears to diminish the incidence and severity of reflex hypotension and bradycardia noted in cerebral angiography. Both Grietz and Tornell (3) and Lundervold and Engeset (7) discussed the bradycardial reactions, but were unable to explain their relationship to the contrast agent. It is unclear what the relationship is between the bradycardia seen in cerebral angiography and the reaction types to intravenous contrast media described here. Nevertheless, the efficacy of atropine as a premedication in the management of bradycardia and hypotension following cerebral angiography is established. The value of atropine in the treatment of the same types of reaction following the use of intravenous contrast me-
UNUSUAL REACTIONS TO INTRAVENOUS CONTRAST MEDIA
Vol. 121
dium is strongly suggested from our limited experience. CASE VIII, however, illustrates some of the problems that can be encountered in the management of this reaction, even with use of atropine. The heart rate of 20/min., never recorded by electrocardiogram, was either a profound sinus bradycardia, a nodal or other supraventricular bradycardia, or an idioventricular rhythm. It responded immediately to intravenous atropine, converting to a normal sinus rhythm within minutes. If the drop in blood pressure was solely related to a diminished cardiac output secondary to the bradycardia, it should have returned to normal coincident with the resumption of the normal sinus rhythm. The persistence of the hypotension suggests several alternative possibilities: (a) Other non-vagal causal factors produced peripheral vasodilatation; or (b) The response of a vagovagal reaction to atropine is dose dependent, with cardiac rate being most sensitive and the peripheral resistance less sensitive. If this is true, doses in the range of 1 to 2 mg would be more appropriate; there is some pharmacologic evidence to support this (2).
Department of Radiology Mallinckrodt Institute of Radiology 510 S. Kingshighway St. Louis, Mo. 63110
REFERENCES 1. Friedenberg CK: Diseases of the Heart. Philadelphia, Saunders, 3d ed, 1966, pp 462-469 2. Goodman LS, Gilman S: The Pharmacological Basis of Therapeutics. London, Macmillan, 4th ed, 1970, pp 530-531 3. Greitz T, Tornel! G: Bradycardial reactions during cerebral angiography. Acta Radial 270:75-86, 1967 4. Lasser EC, Lang JH: Contrast-Protein interactions. Invest Radiol 5:446-451, Nov 1970 5. LasserEC, Lang JH: Inhibitionof acetylcholinesterase by some organic contrast media. Invest RadioI1:237-242, May 1966 6. Lasser EC, Walters AJ, Lang WH: An experimental basis for histamine release in contrast material reactions. Radiology 110:49-59, Jan 1974 7. Lundervold A, Engeset A: Recordings of EEG, ECG, EMGand intraarterial blood pressure during cerebral angiography. Acta Radiol 270:198-207, 1967 8. Modell W: Drugs of Choice. St. Louis, Mosby, 1974-75, pp 299-302 9. Sim VM: Diagnosis and therapy for anticholinesterase poisoning. JAMA 192:143-144, May 1965 10. Viner NA, RhamyRK: Anaphylaxismanifestedby hypotension alone. J UroI113:108-110, Jan 1975
The management of most severe reactions to intravenous water-soluble contrast agents involves the use of epinephrine, aminophyllin, and other pharmacologic agents (glucocorticoids, antihistamines)as complications develop, as well as supportive measures such as oxygen, intravenous fluids, assisted ventilation, external cardiac massage, and defibrillation. Our experience indicates that one type of reaction, infrequent in occurrence, with the combined
Case Dose No. Method
Contrast Medium
Time Onset Reaction (min)
30-ml Bolus
Conray60
3
250-ml Infusion
Hypaque25
8
300-ml lnfusion
Conray
4
75-ml Bolus
Conray400
10
5
50-ml Bolus
Conray60
6
150-ml Infusion
Cholegrafin
7
100-ml Infusion
Renografin-30
4
8
50-ml Bolus
Renografin-60
2
1
2
3
15
Progress of Cases Hrt. Rate
Bid. Press. Symptom Sequence
Initial
---Reaction
Apprehension Flushing Unconscious Convulsions Apnea
120/80
70
70/40
45
Restlessness Dyspnea Unconscious
120/70
92
30/0
30
Restlessness
115/84
82
Diaphoresis Unconscious
40/0
54
Restlessness Diaphoresis
130/100 80
3
Restlessness Apprehension
125/85
20
Restlessness Apprehension Abdominal Cramping
..-
._-------_.~_._-----_
70/40
55
80/... 154/80
50 80
100/60
60
Apprehension Clammy
110/70
80
72/34
42
Vomiting Erythema Restlessness
145/95
82 ---
50/0
Diagnostic Radiology
signs of bradycardia and hypotension, should be treated with intramuscular or preferably intravenous atropine in the range of 0.5 to 2.0 mg as the initial drug of choice, followed by careful monitoring of the patient's response. Prompt recognition and treatment may avert further complications and the use of inappropriate or nonspecific drugs.
SUMMARY
Table I:
7
20
Treatment
Time to Return Normal BP & Heart Rate
Comments
Epinephrine Steroids Antihistamine
45 min.
No sequelae
Saline Steroids Epinephrine
60 min.
No sequelae
Mannitol Steroids Antihistamine Epinephrine Norepinephrine Drip
20 hrs.
Resistant hypotension Acute myocardial infarction Acute renal failure Subsequent urography
Saline 0.5 mg atropine IV
10 min.
No sequelae
0.5 mg atropine IV
10 min.
No sequelae
0.6 mg atropine 1M
30 min.
No sequelae
8 min.
No sequelae
5% D/W 0.75 mg atropine IV Ringer's Albumisol Saline 0.8 mg atropine IV
--._----
3 min. Heart rate 30 min. B.P.
No sequelae
--_._'-
--~-~---_._._._---~---
