i An update to this article is included at the end

Renal infarction secondary to ketamine a”>American Journal of Emergency Medicine 31 (2013) 1153.e3-1153.e5

Contents lists available at SciVerse ScienceDirect

American Journal of Emergency Medicine

journal homepage: locate/ ajem

Case Report

Renal infarction secondary to Ketamine abuse

Abstract

Renal infarction is an uncommon condition that resulted from inadequate perfusion of the kidney and is easily missed diagnosed due to its nonspecific clinical presentations. Major risk factors for renal infarction are atrial fibrillation, previous embolism, and ischemic and valvular heart disease. Progressive decrease in renal function or even death can occur if renal infarction is not diagnosed accurately and promptly. Ketamine abuse may cause variable urinary tract injury. However, renal infarction caused by ketamine abuse has never been reported. To our knowledge, this is the first documented case of renal infarction following nasal insufflation of ketamine.

Renal infarction is an uncommon condition and easily missed diagnosed [1]. The incidence of renal infarction is estimated about 0.004% to 0.007% in the emergency departments (EDs) [2]. Common etiologies of renal infarction include intrinsic arterial disorders of the kidney, thromboembolism, renal disease, and trauma [1]. Renal infarction can also result from some unusual condition such as hypercoagulopathy, vasculitis, Ehlers-Danlos syndrome, fibromuscu- lar dysplasia of vessels, severe blunt trauma, paradoxical embolism, endocarditis, cholesterol embolism [3], malignancy, and cocaine abuse [4]. Lower urinary tract injury is a common complication of ketamine abuse [5]. However, renal infarction caused by ketamine abuse has never been reported.

A 20-year-old woman presented to our ED with left flank pain persistently for 3 weeks, and symptoms progressed in the past few days. She denied having fever, dysuria, hematuria, or difficulty in micturition. Her blood pressure, heart rate, temperature, respiratory rate, and oxygen saturation were normal. Physical examination was unremarkable except for left costovertebral angle tenderness.

The patient has history of ketamine abuse for approximately 4 years. Ketamine has been used by nasal insufflation about 2 to 5 g/d without combination with other medication. She had even with- drawn ketamine a year ago because of ketamine cystitis including the symptoms of severe frequency, urgency, nocturia, urinary incontinence, gross hematuria, and bladder pain. However, she began to use ketamine again since 2 months ago. There was no history of heart disease, coagulation disorder, vessels disorder, or other systemic disease.

Laboratory examination showed a white blood cell count of 9190/uL (68% neutrophils), serum creatinine of 0.6 mg/dL, prothrombin time of

10.2 seconds, partial prothrombin time of 33.2 seconds, International normalized ratio of 0.9, and lactate dehydrogenase of 480 U/L. A urinalysis showed 2 to 5 red blood cells per high-power field and 2 to 5 white blood cells per high-power field and no proteinuria or casts. Ketamine abuse was confirmed by positive urine test.

A computerized tomographic (CT) scan with intravenous contrast injection discovered several wedge-shaped, heterogeneous areas with

decreased enhancement of the left kidney concomitant with hydro- ureteronephrosis (Fig. 1A). It was compatible with renal infarction. Cystoscopy showed multiple petechial hemorrhages of the bladder wall and multiple erythematous patches with bleeding after hydro- distention (Fig. 2). It was compatible with ketamine cystitis.

The 12-lead electrocardiogram and transthoracic echocardiogram showed unremarkable. Further screening for hypercoagulopathy and autoimmune disorders showed normal levels of protein C, Protein S, Factor V Leiden, Factor VIII, Factor IX, Factor XI, antithrombin III, and

Fig. 1. A, Computed tomography of the abdomen showed several wedge-shaped, heterogeneous areas with markedly decreased Contrast enhancement of the left kidney (arrow). B, The 9-month later follow-up CT scan showed progressed renal infarction with huge area of decreased contrast uptake of the left kidney.

0735-6757/$ - see front matter (C) 2013

1153.e4 J-L. Chen et al. / American Journal of Emergency Medicine 31 (2013) 1153.e3-1153.e5

which is a relaxing factor of vascular contractibility [9]. Subsequently, decrease in the synthesis of NO may cause vascular contraction. In the study of pulmonary artery of dogs, ketamine reduced the level of Intracellular calcium concentration and subsequently reduced intra- cellular NO synthesis [10]. We suppose that elimination of NO synthesis resulted from the effects of ketamine may cause vascular contraction. In cerebral arteries of the dogs, ketamine has been shown to induce vascular contracture [11]. Therefore, we hypothe- size that ketamine abuse-related renal infarction resulted from intense vasospasm.

Several treatment strategies have been stated including observa- tion, anticoagulation, Endovascular therapy (thrombolysis, throm- bectomy, or angioplasty) and surgery [12-16]. In our patient, anticoagulants were given for initial management. She was dis- charged asymptomatic on day 6 with INR level between 2 and 3 [13]. However, the renal infarction progressed after 9 months as she constantly used ketamine. This indicates that ketamine withdraw is crucial for renal infarction treatment.

In conclusion, the pathophysiology of ketamine-related renal infarction is still not clear. We infer that vasospasm may be a possible mechanism of ketamine abuse-related renal infarction. Further studies are needed to delineate the possible etiology. In patients with atypical flank or abdominal pain, who have a history of ketamine abuse, renal infarction should be considered in the differential diagnosis and a CT scan with contrast helps confirm the diagnosis. Ketamine cessation is critical to prevent further damage of the kidney.

Jin-Li Chen MD Tai-Lung Cha MD, PhD Sheng-Tang Wu MD Shou-Hung Tang MD Chih-Wei Tsao MD

En Meng MD, PhD Division of Urology, Department of Surgery, Tri-Service General Hospital National Defense Medical Center, Taipei 114, Taiwan, R.O.C.

E-mail address: [email protected] http://dx.doi.org/10.1016/j.ajem.2013.02.036

Fig. 2. Cystoscopy showed multiple petechial hemorrhages of the bladder wall (A) and erythematous patches with bleeding after hydrodistention (B).

lipid profile. Rheumatoid factor, anticardiolipin antibody, antinuclear antibody, and antineutrophil cytoplasmic antibody were all negative. low-molecular-weight heparin was administered intravenously for 3 days and followed by oral antiplatelet (warfarin). After stabilization of INR level between 2 and 3, she was discharged on day 6. Unfortunately, she failed to follow-up and kept using ketamine. Nine months later, the patient came back to our ED with general weakness and poor renal function. A follow-up CT scan showed

progressive renal infarction of the left kidney (Fig. 1B).

intravenous injection and nasal insufflation of cocaine have been demonstrated to cause renal infarction [4,6]. However, renal infarction as a complication of ketamine abuse has never been reported. Ketamine was the only vasoactive substance used, which led us to postulate that the drug played a role in our patient’s renal infarction. Ketamine is an anesthetic medication, which is used as an intravenous induction for anesthesia. It can induce modulatory stimulations on central nervous system and sympathetic nervous system [7,8]. Vascular Endothelial cells produce Nitric oxide ,

References

1. Antopolsky M, Simanovsky N, Stalnikowicz R, Salameh S, Hiller N. Renal infarction in the ED: 10-year experience and review of the literature. Am J Emerg Med 2012;30:1055-60.
2. Chang HY, Yang YN. Silent ST segment elevation myocardial infarction with multi- segmental renal infarction: an Unusual presentation. Intern Med 2011;50:723-5.
3. Domanovits H, Paulis M, Nikfardjam M, Meron G, Kurkciyan I, Bankier AA, et al. Acute renal infarction. Clinical characteristics of 17 patients. Medicine 1999;78: 386-94.
4. Goodman PE, Rennie WP. Renal infarction secondary to nasal insufflation of cocaine. Am J Emerg Med 1995;13:421-3.
5. Chu PS, Ma WK, Wong SC, Chu RW, Cheng CH, Wong S, et al. The destruction of the lower urinary tract by ketamine abuse: a new syndrome? BJU Int 2008;102: 1616-22.
6. Wohlman RA. Renal Artery thrombosis and embolization associated with intravenous cocaine injection. South Med J 1987;80:928-30.
7. Cook DJ, Carton EG, Housmans PR. Mechanism of the positive inotropic effect of ketamine in isolated ferret ventricular papillary muscle. Anesthesiology 1991;74: 880-8.
8. Reich DL, Silvay G. Ketamine: an update on the first twenty-five years of clinical experience. Can J Anaesth 1989;36:186-97.
9. Freedman JE, Loscalzo J. endothelial dysfunction and atherothrombotic occlusive disease. Drugs 1997;54(Suppl 3):41-9 [discussion 49-50].
10. Ogawa K, Tanaka S, Murray PA. Inhibitory effects of etomidate and ketamine on endothelium-dependent relaxation in canine pulmonary artery. Anesthesiology 2001;94:668-77.
11. Altura BT, Quirion R, Pert CB, Altura BM. Phencyclidine (“angel dust”) analogs and sigma opiate benzomorphans cause cerebral arterial spasm. Proc Natl Acad Sci U S A 1983;80:865-9.
12. Cheng BC, Ko SF, Chuang FR, Lee CH, Chen JB, Hsu KT. Successful management of acute renal artery thromboembolism by intra-arterial thrombolytic therapy with recombinant tissue plasminogen activator. Ren Fail 2003;25:665-70.

    J-L. Chen et al. / American Journal of Emergency Medicine 31 (2013) 1153.e3-1153.e5 1153.e5

    Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuunemann HJ. Executive summary: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 Suppl):7S-47S.

13. Haas CA, Dinchman KH, Nasrallah PF, Spirnak JP. Traumatic renal artery occlusion: a 15-year review. J Trauma 1998;45:557-61.
14. Nakayama T, Okaneya T, Kinebuchi Y, Murata Y, Iizuka K. Thrombolytic therapy for traumatic unilateral Renal artery thrombosis. Int J Urol 2006;13: 168-70.
15. Siablis D, Liatsikos EN, Goumenos D, Karnabatidis D, Voudoukis T, Barbalias G, et al. Percutaneous rheolytic thrombectomy for treatment of acute renal-artery thrombosis. J Endourol 2005;19:68-71.

    Update

    American Journal of Emergency Medicine

    Volume 32, Issue 2, February 2014, Page 190

    DOI: https://doi.org/10.1016/j.ajem.2013.09.041

    

    Erratum

    Contents lists available at ScienceDirect

    American Journal of Emergency Medicine

    journal homepage: www. elsevier.com/ locate/ajem

    American Journal of Emergency Medicine 32 (2014) 190

    

    In the article, “Renal infarction secondary to ketamine abuse” in Am J Emerg Med 2013;31:1153, the name of the first author was incorrectly listed. The Correct byline is:

    Chin-Li Chen MD

    Tai-Lung Cha MD, PhD Sheng-Tang Wu MD Shou-Hung Tang MD Chih-Wei Tsao MD

    En Meng MD, PhD

    Division of Urology, Department of Surgery, Tri-Service General Hospital National Defense Medical Center, Taipei 114, Taiwan R.O.C.

    E-mail address: [email protected]

    DOI of original article: http://dx.doi.org/10.1016/j.ajem.2013.02.036.

    0735-6757/$ - see front matter (C) 2013 http://dx.doi.org/10.1016/j.ajem.2013.09.041