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Abstract: Intractable hiccups in transplanted patients may be caused by various hiccups; transplantation; adverse e¡ects; medical conditions including infections.We report a case of a 44 -year-old man who corticosteroids; esophagitis; pulmonary abscess su¡ered from intractable hiccups after cadaveric kidney transplantation.We identi¢ed 3 di¡erent hiccup periods with di¡erent causes: 1) steroid and anesthetics use, 2) severe ulcerose herpetic and mycotic esophagitis, and 3) pleuropneumonia caused by nosocomial methicillin-resistant Staphylococcus epidermidis and pulmonary abscess requiring thoracic surgery.
2Internal Clinic, MedicalFaculty, University of PJ Hiccups, or singultus, are involuntary spasms of the diaphragm and in- tercostal muscles causing sudden inspiration and a characteristic sound.
They are usually benign and self-resolving. However, in some cases chronic or recurrent hiccups are troublesome for the patient as well as Transplantation DepartmentFaculty Hospital of L. Pasteur for the clinician (1). Persisting or recurrent hiccups that do not respond Tr. SNP 1, 040 11 Kos›iceSlovak Republic to di¡erent therapeutic approaches are often a symptom of severe disor- Tel: 1 421 903 193089Fax: 1 421 55 6444664 der (1^5). Table 1 shows the most important and most common clinical e-mail: rosenberger_ conditions leading to persistent or repeated hiccups (1, 2, 4^6).
A cadaveric kidney was transplanted into a 44 -year-old man. His immu- nosuppressive regimen included a standardized protocol with steroids, cyclosporine, and mycophenolate mofetil. The postoperative course was characterized by primary graft function without any complications ex- cept for recurring hiccup episodes that began immediately after the pa- tient woke up from anesthesia. These hiccups responded to treatment with p.o. metoclopramide, and they were not severe. Presentation and course suggested a medication-induced etiology related to steroid induc- Received 2 March 2005, revised 14 June and 8 July 2005, The patient was discharged from the hospital on the 10th day, but 1 day Copyright & Blackwell Munksgaard 2005 later he was re-admitted because of dyspnea associated with very severe Transplant Infectious Disease . ISSN 1398 -2273 attacks of hiccuping. A chest and abdominal x-ray scan was negative, as was abdominal ultrasonography, despite the dramatic course. When the Rosenberger et al: Renal transplant patient with hiccups Causes of persistent or recurrent hiccups infrequent hiccups and good therapeutic response to metoclopramide.
The start of hiccups immediately after transplantation leads us to sus- pect the anesthetic and/or methylprednisolone as the causative agents (1, 8, 9). The latter drug was given during the 4 days following transplant, Diaphragmatic herniation, liver tumor (4, 5) and then it was replaced with prednisone.We failed to identify any other Esophageal tumor or re£ux; gastric distention, ulcer, tumor, or bleeding Neurological disorders a¡ecting brain or phrenic nerves (tumors, injury) Symptoms associated with singultus depending on etiology, and recom- Pharmacological agents (corticosteroids, anesthetics, ethanol, barbiturates, midazolam, methyldopa, morphine) (1, 5) Pleural and pulmonary infections (abscess, tuberculosis, pneumonia, Esophagitis (Candida sp., Herpes simplex) (2, 5) Encephalitis, brain abscess (HIV, toxoplasmosis) (4, 5) patient reported retrosternal pain and odynophagia that were previously not present, he underwent esophagogastroscopy, which revealed severe ulcerative herpetic and candidal esophagitis. After treatment with acy- clovir, £uconazole, and omeprazole, the hiccups faded away during the During the second hospitalization, the patient was a¡ected by severe acute antibody-mediated rejection Grade IIA of the Ban¡ 97 working classi¢cation of kidney transplant pathology (7 ). Because of corticoster- oid resistance, we decided to treat the patient with a course of high-vol- ume plasmapheresis and the replacement of cyclosporine with tacroli- mus. During the period of the anti-rejection treatment, the patient ac- quired nosocomial pleuropneumonia with no other agent identi¢ed but coagulase-negative methicillin-resistant Staphylococcus epidermidis (MRSE). Despite combined antibiotic treatment (initially merope- nem 1 clindamycin, but after ¢nding MRSE in the bronchoalveolar lavage £uid, then vancomycin 500 mg/48 h), the patient’s status deterio- rated. A computed tomography scan revealed an abscess in the right lower pulmonary lobe. At this time, the patient again reported new epi- sodes of hiccups that became more and more severe. The abscess was successfully removed by a thoracotomy, after which the patient’s status improved rapidly and the hiccups ¢nally disappeared.
CT, computed tomography; MRI, magnetic resonance imaging.
Our patient su¡ered from recurring episodes of hiccups, which could be divided into 3 di¡erent periods. The ¢rst period was represented by Transplant Infectious Disease 2005: 7: 86^88 Rosenberger et al: Renal transplant patient with hiccups The second time hiccups appeared was during a bout of esophagitis.
infections and tumors (gastrointestinal lymphomas) are the most likely The immunocompromised patient is predisposed to infectious causes. Neurological causes known from oncology are unlikely to be re- esophagitis involving herpes simplex and Candida sp., which is often sponsible for hiccups in transplanted patients, as are metabolic and elec- accompanied by odynophagia, retrosternal pain, hiccups, and pyrosis trolyte disturbances, because patients become accustomed to them.
(2, 10^12). After treatment of the cause, the endoscopic changes disap- However, brain abscesses as encountered in immunocompromised hu- peared and all symptoms (including hiccups) ceased as well.
man immunode¢ciency virus-infected patients with AIDS can be a rare After a hiccup-free period, singultus appeared again and its inten- cause of intractable hiccups (16, 17 ). Table 2 refers to the most common sity increased with the severity of pulmonary changes. In this clinical symptoms associated with the causes of hiccups and suggests a period, the hiccups were de¢nitely of pulmonary origin (1, 13), and their response to di¡erent drugs (metoclopramide, chlorpromazine, haloperidol, lidocaine, nifedipine, omeprazole) was weak and short termed. After discovery and removal of a supradiaphragmatic abscess, the hiccups immediately discontinued and they did not appear again.
Few studies have been published about hiccups in transplant patients.
We were able to identify 8 articles using a systematic review with the key words ‘hiccups’ and ‘transplantation.’ F|ve of these articles included pa- Usually benign and self-resolving, hiccups can sometimes indicate se- tients with chronic renal failure in the dialysis program, but no patients vere underlying problems, and should be taken into consideration in after transplantation. The 3 remaining articles are case reports (11, 14, the clinician’s di¡erential diagnosis and therapeutic approach. Espe- 15). This lack of evidence-based information makes it impossible to fol- cially in transplant patients, who receive multiple drugs and tend to be low any guidelines and allows only approximations based on experience very susceptible to various pulmonary, abdominal, and esophageal from other ¢elds of medicine, especially oncology. Based on all known infections, the presence of hiccups needs careful examination. The data, we may conclude that infections (esophagitis, pleuropneumonia, recommended diagnostic algorithm should include careful analysis pulmonary, and liver abscess) and adverse e¡ects of various drugs (ster- of medication and other symptoms, physical examination, abdominal oids, anesthetics) are the most probable causes of hiccups in trans- ultrasound, chest x-ray scan, and esophago-gastro-duodenoscopic planted patients in the early post-transplant period. In later periods, 1. WALKER P,WATANABE S, BRUERA E. Baclofen ^ 12. POLLACK MJ. Intractable hiccups: a serious et al. International standardization of criteria sign of underlying systemic disease. J Clin for the histologic diagnosis of renal allograft rejection: the Ban¡ working classi¢cation of kidney transplant pathology. Kidney Int 1993: presenting as singultus. South Med J 2004: 8. CEROSIMO RJ, BROPHY MP. Hiccups with high 14. CHAND EM, NASIR A, PASCAL RR. Pathologic dose dexamethasone administration. Cancer quiz case. Refractory hiccups in a man after liver transplantation for hepatitis C. Arch cisapride, omeprazole and baclofen. ClinTher 15. NGUYEN JD, DUNLEAVY K, CARRASQUILLO JA, CHEN CC. F-18 £uorodeoxyglucose positron recipients of renal homografts. Anesth Analg emission tomographic imaging in a patient treatment for intractable hiccups. Am J Med with persistent hiccups. Clin Nucl Med 2004: 5. LAUNOIS S, BIZEC JL,WHITELAW WA, CABANE 16. FRIEDLAND JS. Hiccups, toxoplasmosis, and J, DERENNE PJ. Hiccup in adults: an overview.
RICHTER JE, eds. The Esophagus (3rd edn).
AIDS. Clin Infect Dis 1994: 18: 835.
Philadelphia: Lippincott Williams & Wilkins, 17. JANSEN PH, JOOSTEN EM,VINGERHOETS HM.
Persistent periodic hiccups following brain 11. CAIN JS, AMEND W. Herpetic esophagitis abscess: a case report. J Neurol Neurosurg causing intractable hiccups. Ann Intern Med Transplant Infectious Disease 2005: 7: 86^88


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