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Renal papillary necrosis following emergency department treatment of migraine
PI1 SO736-4679(96) 00036-4
coiugy in Emergency Medicine
RENAL
PAPILLARY
NECROSIS FOLLOWING EI’ilEMCY TREATMENT OF MMRAtNE
T
Michael D. Witting, MD Assistant Professor, Division of Emergency Medicine, Department of Surgery, University of Maryland Medical Center, Baltimore, Maryland Reprint Address: Dr. Michael Witting, Division of Emergency Medicine, University of Maryland Medical Center, 419 W. Redwood St., Suite 280, Baltimore, MD 21201
0 Abstract--New medications have lessened the need for narcotic medications in the acute treatment of migraine. Some of these new medications include parenteral dihydroergotamine (DDE), sumatriptan, and ketorolac. Treatment failures still occur, though, and some cases necessitate adding a second agent to one that has been ineffective. We report a case of a 46-year-old man who suffered renal papillary necrosis 12 days after receiving parenteral DHK, sumatriptan, and ketorolac for treatment of a severe migraine headache. There were no signs of an adverse drug reaction at the time of his emergency department visit. The case illustrates a potential hazard of this combination in the acute treatment of migraine. C Keywords-migraine; kidney papillary necrosis; sumatriptan; dihydroergotamine; ketorolac
CASE REPORT
A 46year-old male physician with a history of migraine headaches presented to the emergency department (ED) after experiencing the gradual onset of a severe headache,characteristic of his migraines, associated with photophobia, nausea,and vomiting. He denied any focal neurologic symptoms or syncope. His medical history was notable only for migraine. His migraines had decreasedin frequency to one every few years. In the past, he had taken a non-steroidal anti-inflammatory drug (NSAID) early in the course of his headaches, but he could not recall the drug’s name and did not have any to use for this headache.He had no history of renal disease,hypertension, diabetes, RECEIVED: ACCEPTED
30 June 1995; FINAL SUBMISSION RECEIVED: : 3 November 1995
coronary artery disease,or cerebrovascular disease.He had no family history of coronary artery disease, and no history of smoking. He was taking no daily medications and had not taken anything for this headache prior to his ED visit. In prior ED visits for migraine headaches,he had received meperidine, which successfully relieved his pain, but he wished to avoid repeating this treatment because of the sedation it induced. Physical examination revealed an alert patient in acute distress, having difficulty standing because of the pain. He was helped to a stretcher, and the vital signs taken were normal. Other than photophobia, the physical examination, including funduscopic and neurologic assessments,was normal. Table 1 summarizes the treatment administered in the emergency department. During his ED stay, the patient’s blood pressure was monitored frequently and never exceeded the normal range. He had no complaints of chest pain or shortness of breath nor any complaints related to his extremities. Following evaluation and treatment, he was discharged from the ED. The following morning, the headachehad resolved. He continued to be asymptomatic and did not take any medications until 12 days later, when he had acute onset of severe right flank pain, and returned to the ED. An intravenous pyelogram (IVP) at this time revealed obstruction of the right distal ureter. A double-J stem was placed, the obstructing material was removed, and a pathologist found the material to be necrotic renal papillary tissue. Serum creatinine and urinalysis were both normal, and a urine culture was negative. The double-J stent was removed without complica_.--“--__l. -..---I.--. 11 October 1995: 373
374
M. D. Witting
Table 1. Emergency Department with Severe Migraine
Minutes After Arrival
Treatment Sumatriptan, 6 mg SC Prophenazine, 10 mg IV Dihydroergotamine, 1 mg IM Ketorolac, 60 mg IM Sumatriptan, 6 mg SC Meperidine, 50 mg IM SC, subcutaneously;
Treatment
20 30 90 115 120 140
IV, intravenously;
of a Patient
Response No relief No relief Vomiting, No relief No relief Relief
no relief
IM, intramuscularly.
tions after 1 week. Three days later, however, the patient suffered acute severe left flank pain, which again was caused by obstructing renal papillary necrotic debris, and required another stent placement. This second stent was later removed with no complications. His serum creatinine remained normal. Weeks after the patient’s complications had resolved, he was again questioned about the use of NSAIDs. He confirmed that he did not chronically use NSAIDs and did not take any shortly before or after his initial visit to the emergency department.
DISCUSSION Renal papillary necrosis (RPN) is a tubulointerstitial nephropathy accompanied by compromised renal blood flow, resulting in necrosis in segments of the renal papillae. It previously has been termed “renal medullary necrosis,’ ’ ‘ ‘renal necrotizing papillitis, ’ ’ ‘ ‘necrotizing pyelonephritis,’ ’ and ‘ ‘papillary necrosis.” It rarely occurs without specific predisposing clinical conditions: diabetes mellitus, urinary tract obstruction, pyelonephritis, non-steroidal anti-inflammatory drug abuse, sickle cell hemoglobinopathy, renal transplant rejection, or cirrhosis of the liver ( 1) . The papillary blood supply is provided primarily by the vasa rectae. As the vasa rectae descend toward the tip of the papillae, their caliber and number decrease, and the blood supply to this area is relatively poor. Because of the frequent association between papillary necrosis and pyelonephritis, RPN was once thought to be caused by infection ( 1). It is now held, however, that RPN is caused by ischemic insult affecting these susceptible areas (2,3). The clinical features of RPN are related to the necrotic renal papillae. The necrotic tissue can serve as a nidus for infection; it can slough and cause obstruction; or it can become a nidus for calculus formation. Its clinical features resemble those of pyelonephritis
or ureteral obstruction. Loss of renal function is infrequent, even with bilateral necrosis. The time course of RPN can vary from an acute rapidly-progressive lifethreatening illness to one with a protracted course over months to years ( 1) . In many individuals, RPN occurs in the absence of symptoms and is discovered only at autopsy (2). In the United States, the incidence of RPN discovered at autopsies is 0.16% to 0.26% (2). In clinically diagnosed cases,the average age is 53 years, and it is rare in adults below age 40 ( 1) . The patient described in this report had none of the recognized predisposing clinical conditions for RPN. Since the RPN occurred soon after his emergency department visit, it is possible that the medications that he received in the emergency department were causative. Ketorolac, a pyrrolizine carboxylic acid derivative NSAID, is pharmacologically similar to indomethacin (4). Indomethacin has been shown to cause RPN in humans (3,.5,6), and almost all NSAIDs tested in the rat have caused RPN (3 ) . Renal papillary necrosis is commonly seen in patients with “analgesic nephropathy,’ ’ a well-described syndrome resulting from chronic abuse of aspirin or NSAIDs (7)) but RPN has also been seen when NSAIDs are taken according to recommended dosage schedules (3). Inhibition of the prostaglandins responsible for maintenance of renal blood flow may be the mechanism by which aspirin and NSAIDs produce RPN (3,5,6). There have been no reported cases of ketorolac-induced RPN, but serious renal effects have resulted from only a few doses. Several reports of renal failure associated with one to three doses of ketorolac have been published ( 8- 12)) and a prostaglandin-mediated decreasein renal blood flow was the proposed mechanism (8,9,12). Dihydroergotamine (DHE) is a dihydrogenated amino acid alkaloid ( 13). In contrast to ergotamine, an amino acid derivative, DHE exhibits selective venoconstriction and only limited arterial vasoconstriction ( 13- 15) . Ergotism is a syndrome caused by excessive arterial vasoconstriction and usually results in peripheral vascular ischemia ( 15,16), though there have been reports of myocardial ischemia and infarction resulting from ergot derivatives ( 17). Ergotism, previously named “St. Anthony’s Fire,” dates back to the Middle Ages, when ergot alkaloids were consumed in the form of fungus-contaminated rye. Victims sought relief from the burning extremity pain at the shrine of St. Anthony, and many were cured because the trip forced them to change their diet ( 15) . Unlike ergotamine and methylsergide, DHE rarely causesergotism. It hasbeen given to more than 3 million patients in combination with heparin as prophylaxis for deep vein thrombosis. In these patients, given multiple
375
Renal Papiilaty Necrosis After Migraine Therapy
OS-mg dosesof DHE subcutaneously,the overall annual incidence of clinical vasospasmis estimated at 0.001% to 0.003%, and most of these cases of vasospasmoccurred in patientswho had sustainedtrauma,hypotension, sepsis,or end-stageischemia ( 18,19). Treatment protocols for migraine, calling for dosesof 0.5 to 1 mg parenterally and a seconddose (if needed) given within 20 to 60 minutes, have been followed in more than 2000 patients with no clinical vasoconstriction noted (20-22). While vasospasmis rare with DHE, it can occur. An arterial vasoconstrictor effect could have compromised renal blood flow and thus caused RPN in the patient describedin this casereport. There are no reports of renal failure or RPN attributed to any ergot preparations. Sumatriptan, a new medication for migraine, is selective for the cranial arteries but does cause some general arterial vasoconstriction (23). Accordingly, it should be avoided in patients with a history of ischemic heart diseaseor peripheral vascular disease(24-26). The Physician’s Desk Referencecautions againstthe simultaneous useof ’ ‘ergotamine-containing” preparationswith sumatiptan because of the theoretic consideration that the vasoconstrictor effects may be additive (26). While sumatriptan has been used safely in 37 patients already taking oral DHE ( 23 ) , its simultaneoususe with parenteral DHE remains to be evaluated.Indeed,the parenteral form of DHE is more likely to cause vasospasmthan larger oral doses ( 14). There are no reports of RPN attributed to sumatriptan. It is possible,however, that the combination of parenteral DIE and sumatriptan caused a decreasein renal blood flow and thus causedRPN in this patient. It is of concern
that the patient suffered this complication despite having no clinical evidence of vasospasmduring his initial emergency department visit. Meperidine was also used in this case.There are no reports of renal papillary necrosis or renal disease in which meperidine or any other opiate analgesicwas implicated. An animal study of intmmnally administered opioid demonstratedan absenceof effect on renal blood flow (27). It is unlikely that meperidine produced renal papillary necrosisin this caseor contributed to the toxicity of the other medications. The most likely cause of the RPN in this case is an overlap phenomenon. The overlap phenomenon, where multiple renal insults occur simultaneously,hasbeenwell describedin the causationof RPN ( 1) . Volume depletion or other conditions of decreasedrenal blood flow, specifically, are known to predispose patients to NSAIDproduced RPN (3,6). It is likely that the combination of two vasoconstrictorsand a prostaglandin inhibitor selectively depleted the vasarectaeof blood flow in this case, causing RPN. CONCLUSION This case illustrates a potential danger of simultaneous parenteraluseof ketorolac,dihydroergotamine,and sumatriptan. Using an opiate analgesicafter failure of one or two of these agentsmay constitute a safer approach. Acknowledgment-1 would like to thank Linda Kesselring,
MSfor her editorial assistance.
REFERENCES I. Eknoyan G. Renal papillary necrosis: an update. Medicine. 1982;61:55-73. 2. Eknoyan G. Renal papillary necrosis. In Collins N (ed) : Textbook of Nephrology, 2nd edition. Baltimore: Williams & Wilkins: 1989:910-5. 3. Kincaid-Smith P. Effect of non-narcotic analgesics on the kidney. Drugs. 1986;32(Suppl. 4):108-28. 4. McEvoy GK ed. AHFS 95 Drug Information. Bethesda: American Society of Health-System Pharmacists, Inc.; 1995:1330-7. s. Nies AS. Renal effects of nonsteroidal anti-inflammatory drugs. Agents Actions [Suppl]. 1988; 24:95- 106. 6. Kirschenbaum MA, Anderson DA. Nephropathies of nonsteroidal antiinflammatory agents. In: Collins N, ed. Textbook of nephrology. 2nd edn. Baltimore: Williams & Wilkins; 1989: 823-8. 7 Nanra RS. Analgesic-associated nephropathies. In: Collins N, ed. Textbook of nephrology, 2nd edn. Baltimore: Williams & Wilkins; 1989:842-8. 8. Smith K, Halliwell RM, Lawrence S, et al. Acute renal failure associated with intramuscular ketorolac. Anaesth Intensive Care. 1993;21(5):700-3. 9. Boras-Uber LA. Ketorolac-induced acute renal failure (letter). Am J Med. 1992:92:450-2.
10. Adverse Drug Reactions Advisory Committee. Ketorolac and renal failure. Med J Aust. 1993; 159(7):488. 11. Quan DJ, Kayser SR. Ketorolac induced acute renal failure following a single dose. J Toxic01 Clin Toxicol. 1994; 32(3):305-9. 12. Schoch PH, Ranno A, North DS. Acute renal failure in an elderly woman following intramuscular ketorolac administration. Ann Pharmacother. 1992;26:1233-5. 13. Schulman EA, Rosenberg SB. Claudication: An unusual side effect of DHE administration. Headache. 1991;31:237-9. 14. Muller-Schweinitzer E. What is known about the action of dihydroergotamine on the vasculature in man? Int J Clin Pharmacol. 1984;22(12):677-82. 15. Tanner JR. St. Anthony’s Fire, then and now: A case report and historical review. Can J Surg. 1987;30(4):291-3. 16. Harrison TE. Eraotaminism. JACEP. 1978:7:162-9. 17. Galer BS, LiptoiRB, Solomon S, et al. Myocardial &hernia related to ergot alkaloids: a case report and literature review. Headache. 1991;31:446-50. 18. Comerota AJ, White JV. The use of dihydroergotamine and heparin in the prophylaxis of deep venous thrombosis. Chest. 1986; 89[Suppl 5]:389s-5s. 19. Lindblad B. Prophylaxis of postoperative thromboembolism with low dose heparin alone or in combination with dihydroergotamine. Acta Chir Stand Suppl. 1988;543:3 I-42.
376 20. Raskin NH. Modern pharmacotherapy of migraine. Neurol Clinics. 1990;8(4):857-65. 21. Winner P, Dalessio D, Mathew N, et al. Office-based treatment of acute migraine with dihydroergotamine mesylate. Headache. 1993;33:471-5. 22. Robbins L, Remmes A. Outpatient repetitive intravenous dihydroergotamine. Headache. 1993;32:455-8. 23. Henly P, d’Allens H. Subcutaneous sumatriptan in the acute treatment of migraine in patients using dihydroergotamine as prophylaxis. Headache. 1993;33:432-5.
M. D. Witting 24. Hsu VD. Sumatriptan: A new drug for vascular headache. Clin Pharmacol. 1992; 11:919-29. 25. Fox AW, Poe TE: Use and safety of sumatriptan (letter). Clin Pharmacol. 1993; 12:258. 26. 1995 Physicians Desk Reference. Sumatriptan. Montvale NJ: Medical Economics Data Production Company; 1995:855-8. 27. Kapusta DR, Jones SY, DiBona GF. Renal mu opioid receptor mechanisms in regulation of renal function in rats. J Pharmacol Exp Ther. 1991;258:111-7.
coiugy in Emergency Medicine
RENAL
PAPILLARY
NECROSIS FOLLOWING EI’ilEMCY TREATMENT OF MMRAtNE
T
Michael D. Witting, MD Assistant Professor, Division of Emergency Medicine, Department of Surgery, University of Maryland Medical Center, Baltimore, Maryland Reprint Address: Dr. Michael Witting, Division of Emergency Medicine, University of Maryland Medical Center, 419 W. Redwood St., Suite 280, Baltimore, MD 21201
0 Abstract--New medications have lessened the need for narcotic medications in the acute treatment of migraine. Some of these new medications include parenteral dihydroergotamine (DDE), sumatriptan, and ketorolac. Treatment failures still occur, though, and some cases necessitate adding a second agent to one that has been ineffective. We report a case of a 46-year-old man who suffered renal papillary necrosis 12 days after receiving parenteral DHK, sumatriptan, and ketorolac for treatment of a severe migraine headache. There were no signs of an adverse drug reaction at the time of his emergency department visit. The case illustrates a potential hazard of this combination in the acute treatment of migraine. C Keywords-migraine; kidney papillary necrosis; sumatriptan; dihydroergotamine; ketorolac
CASE REPORT
A 46year-old male physician with a history of migraine headaches presented to the emergency department (ED) after experiencing the gradual onset of a severe headache,characteristic of his migraines, associated with photophobia, nausea,and vomiting. He denied any focal neurologic symptoms or syncope. His medical history was notable only for migraine. His migraines had decreasedin frequency to one every few years. In the past, he had taken a non-steroidal anti-inflammatory drug (NSAID) early in the course of his headaches, but he could not recall the drug’s name and did not have any to use for this headache.He had no history of renal disease,hypertension, diabetes, RECEIVED: ACCEPTED
30 June 1995; FINAL SUBMISSION RECEIVED: : 3 November 1995
coronary artery disease,or cerebrovascular disease.He had no family history of coronary artery disease, and no history of smoking. He was taking no daily medications and had not taken anything for this headache prior to his ED visit. In prior ED visits for migraine headaches,he had received meperidine, which successfully relieved his pain, but he wished to avoid repeating this treatment because of the sedation it induced. Physical examination revealed an alert patient in acute distress, having difficulty standing because of the pain. He was helped to a stretcher, and the vital signs taken were normal. Other than photophobia, the physical examination, including funduscopic and neurologic assessments,was normal. Table 1 summarizes the treatment administered in the emergency department. During his ED stay, the patient’s blood pressure was monitored frequently and never exceeded the normal range. He had no complaints of chest pain or shortness of breath nor any complaints related to his extremities. Following evaluation and treatment, he was discharged from the ED. The following morning, the headachehad resolved. He continued to be asymptomatic and did not take any medications until 12 days later, when he had acute onset of severe right flank pain, and returned to the ED. An intravenous pyelogram (IVP) at this time revealed obstruction of the right distal ureter. A double-J stem was placed, the obstructing material was removed, and a pathologist found the material to be necrotic renal papillary tissue. Serum creatinine and urinalysis were both normal, and a urine culture was negative. The double-J stent was removed without complica_.--“--__l. -..---I.--. 11 October 1995: 373
374
M. D. Witting
Table 1. Emergency Department with Severe Migraine
Minutes After Arrival
Treatment Sumatriptan, 6 mg SC Prophenazine, 10 mg IV Dihydroergotamine, 1 mg IM Ketorolac, 60 mg IM Sumatriptan, 6 mg SC Meperidine, 50 mg IM SC, subcutaneously;
Treatment
20 30 90 115 120 140
IV, intravenously;
of a Patient
Response No relief No relief Vomiting, No relief No relief Relief
no relief
IM, intramuscularly.
tions after 1 week. Three days later, however, the patient suffered acute severe left flank pain, which again was caused by obstructing renal papillary necrotic debris, and required another stent placement. This second stent was later removed with no complications. His serum creatinine remained normal. Weeks after the patient’s complications had resolved, he was again questioned about the use of NSAIDs. He confirmed that he did not chronically use NSAIDs and did not take any shortly before or after his initial visit to the emergency department.
DISCUSSION Renal papillary necrosis (RPN) is a tubulointerstitial nephropathy accompanied by compromised renal blood flow, resulting in necrosis in segments of the renal papillae. It previously has been termed “renal medullary necrosis,’ ’ ‘ ‘renal necrotizing papillitis, ’ ’ ‘ ‘necrotizing pyelonephritis,’ ’ and ‘ ‘papillary necrosis.” It rarely occurs without specific predisposing clinical conditions: diabetes mellitus, urinary tract obstruction, pyelonephritis, non-steroidal anti-inflammatory drug abuse, sickle cell hemoglobinopathy, renal transplant rejection, or cirrhosis of the liver ( 1) . The papillary blood supply is provided primarily by the vasa rectae. As the vasa rectae descend toward the tip of the papillae, their caliber and number decrease, and the blood supply to this area is relatively poor. Because of the frequent association between papillary necrosis and pyelonephritis, RPN was once thought to be caused by infection ( 1). It is now held, however, that RPN is caused by ischemic insult affecting these susceptible areas (2,3). The clinical features of RPN are related to the necrotic renal papillae. The necrotic tissue can serve as a nidus for infection; it can slough and cause obstruction; or it can become a nidus for calculus formation. Its clinical features resemble those of pyelonephritis
or ureteral obstruction. Loss of renal function is infrequent, even with bilateral necrosis. The time course of RPN can vary from an acute rapidly-progressive lifethreatening illness to one with a protracted course over months to years ( 1) . In many individuals, RPN occurs in the absence of symptoms and is discovered only at autopsy (2). In the United States, the incidence of RPN discovered at autopsies is 0.16% to 0.26% (2). In clinically diagnosed cases,the average age is 53 years, and it is rare in adults below age 40 ( 1) . The patient described in this report had none of the recognized predisposing clinical conditions for RPN. Since the RPN occurred soon after his emergency department visit, it is possible that the medications that he received in the emergency department were causative. Ketorolac, a pyrrolizine carboxylic acid derivative NSAID, is pharmacologically similar to indomethacin (4). Indomethacin has been shown to cause RPN in humans (3,.5,6), and almost all NSAIDs tested in the rat have caused RPN (3 ) . Renal papillary necrosis is commonly seen in patients with “analgesic nephropathy,’ ’ a well-described syndrome resulting from chronic abuse of aspirin or NSAIDs (7)) but RPN has also been seen when NSAIDs are taken according to recommended dosage schedules (3). Inhibition of the prostaglandins responsible for maintenance of renal blood flow may be the mechanism by which aspirin and NSAIDs produce RPN (3,5,6). There have been no reported cases of ketorolac-induced RPN, but serious renal effects have resulted from only a few doses. Several reports of renal failure associated with one to three doses of ketorolac have been published ( 8- 12)) and a prostaglandin-mediated decreasein renal blood flow was the proposed mechanism (8,9,12). Dihydroergotamine (DHE) is a dihydrogenated amino acid alkaloid ( 13). In contrast to ergotamine, an amino acid derivative, DHE exhibits selective venoconstriction and only limited arterial vasoconstriction ( 13- 15) . Ergotism is a syndrome caused by excessive arterial vasoconstriction and usually results in peripheral vascular ischemia ( 15,16), though there have been reports of myocardial ischemia and infarction resulting from ergot derivatives ( 17). Ergotism, previously named “St. Anthony’s Fire,” dates back to the Middle Ages, when ergot alkaloids were consumed in the form of fungus-contaminated rye. Victims sought relief from the burning extremity pain at the shrine of St. Anthony, and many were cured because the trip forced them to change their diet ( 15) . Unlike ergotamine and methylsergide, DHE rarely causesergotism. It hasbeen given to more than 3 million patients in combination with heparin as prophylaxis for deep vein thrombosis. In these patients, given multiple
375
Renal Papiilaty Necrosis After Migraine Therapy
OS-mg dosesof DHE subcutaneously,the overall annual incidence of clinical vasospasmis estimated at 0.001% to 0.003%, and most of these cases of vasospasmoccurred in patientswho had sustainedtrauma,hypotension, sepsis,or end-stageischemia ( 18,19). Treatment protocols for migraine, calling for dosesof 0.5 to 1 mg parenterally and a seconddose (if needed) given within 20 to 60 minutes, have been followed in more than 2000 patients with no clinical vasoconstriction noted (20-22). While vasospasmis rare with DHE, it can occur. An arterial vasoconstrictor effect could have compromised renal blood flow and thus caused RPN in the patient describedin this casereport. There are no reports of renal failure or RPN attributed to any ergot preparations. Sumatriptan, a new medication for migraine, is selective for the cranial arteries but does cause some general arterial vasoconstriction (23). Accordingly, it should be avoided in patients with a history of ischemic heart diseaseor peripheral vascular disease(24-26). The Physician’s Desk Referencecautions againstthe simultaneous useof ’ ‘ergotamine-containing” preparationswith sumatiptan because of the theoretic consideration that the vasoconstrictor effects may be additive (26). While sumatriptan has been used safely in 37 patients already taking oral DHE ( 23 ) , its simultaneoususe with parenteral DHE remains to be evaluated.Indeed,the parenteral form of DHE is more likely to cause vasospasmthan larger oral doses ( 14). There are no reports of RPN attributed to sumatriptan. It is possible,however, that the combination of parenteral DIE and sumatriptan caused a decreasein renal blood flow and thus causedRPN in this patient. It is of concern
that the patient suffered this complication despite having no clinical evidence of vasospasmduring his initial emergency department visit. Meperidine was also used in this case.There are no reports of renal papillary necrosis or renal disease in which meperidine or any other opiate analgesicwas implicated. An animal study of intmmnally administered opioid demonstratedan absenceof effect on renal blood flow (27). It is unlikely that meperidine produced renal papillary necrosisin this caseor contributed to the toxicity of the other medications. The most likely cause of the RPN in this case is an overlap phenomenon. The overlap phenomenon, where multiple renal insults occur simultaneously,hasbeenwell describedin the causationof RPN ( 1) . Volume depletion or other conditions of decreasedrenal blood flow, specifically, are known to predispose patients to NSAIDproduced RPN (3,6). It is likely that the combination of two vasoconstrictorsand a prostaglandin inhibitor selectively depleted the vasarectaeof blood flow in this case, causing RPN. CONCLUSION This case illustrates a potential danger of simultaneous parenteraluseof ketorolac,dihydroergotamine,and sumatriptan. Using an opiate analgesicafter failure of one or two of these agentsmay constitute a safer approach. Acknowledgment-1 would like to thank Linda Kesselring,
MSfor her editorial assistance.
REFERENCES I. Eknoyan G. Renal papillary necrosis: an update. Medicine. 1982;61:55-73. 2. Eknoyan G. Renal papillary necrosis. In Collins N (ed) : Textbook of Nephrology, 2nd edition. Baltimore: Williams & Wilkins: 1989:910-5. 3. Kincaid-Smith P. Effect of non-narcotic analgesics on the kidney. Drugs. 1986;32(Suppl. 4):108-28. 4. McEvoy GK ed. AHFS 95 Drug Information. Bethesda: American Society of Health-System Pharmacists, Inc.; 1995:1330-7. s. Nies AS. Renal effects of nonsteroidal anti-inflammatory drugs. Agents Actions [Suppl]. 1988; 24:95- 106. 6. Kirschenbaum MA, Anderson DA. Nephropathies of nonsteroidal antiinflammatory agents. In: Collins N, ed. Textbook of nephrology. 2nd edn. Baltimore: Williams & Wilkins; 1989: 823-8. 7 Nanra RS. Analgesic-associated nephropathies. In: Collins N, ed. Textbook of nephrology, 2nd edn. Baltimore: Williams & Wilkins; 1989:842-8. 8. Smith K, Halliwell RM, Lawrence S, et al. Acute renal failure associated with intramuscular ketorolac. Anaesth Intensive Care. 1993;21(5):700-3. 9. Boras-Uber LA. Ketorolac-induced acute renal failure (letter). Am J Med. 1992:92:450-2.
10. Adverse Drug Reactions Advisory Committee. Ketorolac and renal failure. Med J Aust. 1993; 159(7):488. 11. Quan DJ, Kayser SR. Ketorolac induced acute renal failure following a single dose. J Toxic01 Clin Toxicol. 1994; 32(3):305-9. 12. Schoch PH, Ranno A, North DS. Acute renal failure in an elderly woman following intramuscular ketorolac administration. Ann Pharmacother. 1992;26:1233-5. 13. Schulman EA, Rosenberg SB. Claudication: An unusual side effect of DHE administration. Headache. 1991;31:237-9. 14. Muller-Schweinitzer E. What is known about the action of dihydroergotamine on the vasculature in man? Int J Clin Pharmacol. 1984;22(12):677-82. 15. Tanner JR. St. Anthony’s Fire, then and now: A case report and historical review. Can J Surg. 1987;30(4):291-3. 16. Harrison TE. Eraotaminism. JACEP. 1978:7:162-9. 17. Galer BS, LiptoiRB, Solomon S, et al. Myocardial &hernia related to ergot alkaloids: a case report and literature review. Headache. 1991;31:446-50. 18. Comerota AJ, White JV. The use of dihydroergotamine and heparin in the prophylaxis of deep venous thrombosis. Chest. 1986; 89[Suppl 5]:389s-5s. 19. Lindblad B. Prophylaxis of postoperative thromboembolism with low dose heparin alone or in combination with dihydroergotamine. Acta Chir Stand Suppl. 1988;543:3 I-42.
376 20. Raskin NH. Modern pharmacotherapy of migraine. Neurol Clinics. 1990;8(4):857-65. 21. Winner P, Dalessio D, Mathew N, et al. Office-based treatment of acute migraine with dihydroergotamine mesylate. Headache. 1993;33:471-5. 22. Robbins L, Remmes A. Outpatient repetitive intravenous dihydroergotamine. Headache. 1993;32:455-8. 23. Henly P, d’Allens H. Subcutaneous sumatriptan in the acute treatment of migraine in patients using dihydroergotamine as prophylaxis. Headache. 1993;33:432-5.
M. D. Witting 24. Hsu VD. Sumatriptan: A new drug for vascular headache. Clin Pharmacol. 1992; 11:919-29. 25. Fox AW, Poe TE: Use and safety of sumatriptan (letter). Clin Pharmacol. 1993; 12:258. 26. 1995 Physicians Desk Reference. Sumatriptan. Montvale NJ: Medical Economics Data Production Company; 1995:855-8. 27. Kapusta DR, Jones SY, DiBona GF. Renal mu opioid receptor mechanisms in regulation of renal function in rats. J Pharmacol Exp Ther. 1991;258:111-7.