| Abstract|| |
Context: Tetanus is a disease caused by Clostridium tetani . Acute renal failure (ARF) can occur in patients with tetanus and a number of mechanisms may contribute to this, including rhabdomyolysis and autonomic nervous system overactivity. Aims: To investigate the occurrence of ARF and other clinical features in patients with tetanus in Brazil. Settings and Design: Retrospective study of patients with tetanus admitted to Sao Jose Infectious Diseases Hospital, in Fortaleza City, Brazil. Materials and Methods: All patients admitted from January 1999 to December 2003 were included, except those with previously diagnosed renal insufficiency, diabetes mellitus, systemic arterial hypertension, systemic lupus erythematosous, or any other factors not associated with tetanus that could lead to renal dysfunction. We compared survivors with non survivor patients in order to investigate the differences in clinical manifestations and laboratory tests. Statistical Analysis Used: Statistical analysis was performed using SPSS 10.0 for Windows® . Results: A total of 85 patients were included. The mean age was 52 ± 16 years and 82% were male. The main symptoms and signs presented at admission were trismus (68.2%), dysfagia (50.6%), and neck stiffness (41.2%). AFR was found in 10 patients (11.8%). Death occurred in 8 cases (9.4%). Hyperglicemia (OR = 1.014, p = 0.03), hyperkalemia (OR = 3.2, p = 0.04), and thrombocytopenia (OR = 1.000, p = 0.03) were associated with increased mortality. ARF was not associated with death (p>0.5). Conclusions: ARF is an important complication of tetanus, which was not associated with death. Hyperglicemia, hyperkalemia, and thrombocytopenia seem to increase mortality.
Keywords: Acute renal failure, infectious diseases, prognosis, symptoms, tetanus
|How to cite this article:|
Moura Filho FR, Mendonca PR, Lima EB, Silva JS, Pinho ML, Mota RM, Silva GB, Daher EF. Acute renal failure and other clinical features in tetanus patients from northeastern Brazil. Ann Trop Med Public Health 2008;1:52-5
Tetanus is a nervous system disorder characterized by severe muscle spasms caused by the neurotoxin tetanospasmin produced by Clostridium tetani , a Gram-positive bacillus spore-forming obligate anaerobe whose natural habit is soil. , This toxin is usually acquired through the contamination of wounds with soil, manure, or rusty metal. 
|How to cite this URL:|
Moura Filho FR, Mendonca PR, Lima EB, Silva JS, Pinho ML, Mota RM, Silva GB, Daher EF. Acute renal failure and other clinical features in tetanus patients from northeastern Brazil. Ann Trop Med Public Health [serial online] 2008 [cited 2020 Oct 31];1:52-5. Available from: https://www.atmph.org/text.asp?2008/1/2/52/50684
Tetanospasmin has a predominant effect on inhibitory neurons inhibiting the release of glycine and gamma aminobutyric acid (GABA). ,, Uncontrolled disinhibited efferent discharge from motor neurones in the cord and brainstem lead to intense muscular rigidity and spasm, which may mimic convulsions. Disinhibited autonomic discharge leads to disturbances in autonomic control, with sympathetic overactivity and excessive plasma catecholamine levels.  Neuronal binding of toxins is thought to be irreversible. Recovery requires the growth of new nerve terminals, which explains the prolonged duration of tetanus. , The incubation period varies from 3-21 days, with an average of 8 days. 
In the most common form of tetanus, the first sign is spasm of the jaw muscles, followed by stiffness of the neck, difficulty in swallowing, and stiffness of the abdominal muscles. ,, Other signs include fever, sweating, hypertension, and tachycardia. Laryngospasm is a complication that can lead to interference with breathing and asphyxia.  Patients can also break their spine or long bones due to convulsions.  Other possible complications include hypotension, arrhythmias, and secondary infections, which are common because of a prolonged hospital stay. ,, In addition, altered renal physiology may be seen. 
Acute renal failure (ARF) can occur with tetanus and a number of mechanisms may contribute to this, including rhabdomyolysis and autonomic nervous system overactivity. ,,,, ARF due to tetanus is high in certain countries such as Brazil, where some studies have reported ARF in 34% of the cases.  Studies have already shown that up to 50% of patients with tetanus have a glomerular filtration rate (GFR) lower than 50 mL/min in the first or second week of hospitalization. This finding seems to be related to autonomic nervous system (ANS) overactivity, characterized by intense variations in systolic and diastolic blood pressure, increased heart rate, and elevated urinary metanephrine excretion. In some patients, blood pressure varies widely and terminal patients may develop hypotension and cold periphery. Renal glycosuria in euglycemic tetanus patients was also found and is probably related to tenospasmin. Tetanus-induced ARF is usually mild, non oliguric, has early onset, and is not related to the severity of the disease. 
In Brazil, approximately 1,500 cases are reported each year, and case mortality occurs at a rate of 1.6 cases per 100,000 inhabitants.  In developed countries, the incidence is as low as 50 to 70 cases each year. ,,
As tetanus still has a high incidence and mortality rate (around 30% in Brazil),  it is important to identify its complications in order to manage them as soon as possible and prevent unfavorable outcomes. ,,
The aim of this study was to describe the occurrence of ARF in tetanus and to investigate the factors associated with death.
| Materials and Methods|| |
This is a retrospective study including all patients with tetanus admitted to Sao Jose Infectious Diseases Hospital, in Fortaleza City, Brazil from January 1999 to December 2003. Clinical and laboratory features during the hospital stay were analyzed. A standardized case investigation form was used to complete demographical, epidemiological, clinical, and laboratory data. Serum concentration of urea, creatinine, potassium, sodium, and complete blood count were recorded at admission. ARF was defined as an increase of serum creatinine concentration by more than 50% or greater than 0.5 mg/dL above baseline. A comparison between survivors and non survivors was performed.
The inclusion criteria were patients above 18 years of age with a diagnosis of tetanus admitted during the time period mentioned above. The exclusion criteria were patients who had been previously diagnosed with renal insufficiency, diabetes mellitus, systemic arterial hypertension, systemic lupus erythematosous, as well as those who either were taking any nephotoxic drug or had any other factors not associated with tetanus that could lead to renal dysfunction. The study was approved by the Ethics Committee of Sao Jose Infectious Diseases Hospital.
The statistical analysis consisted of univariate and multivariate analyses of clinical and laboratory data performed using SPSS 10.0 for Windows® (SPSS Inc. Chicago, IL, USA). Groups were compared by using student's t-test and Mann-Whitney. test when appropriated.The analysis of association between death and the categorized risk factors was done through the Fischer's exact test, Pearson's chi square test, and verisimilitude ratio test. A logistic regression model was used for quantitative variables. Adjusted odds ratio and 95% confidence interval were calculated. The descriptive values below 5% (p value < 0.05) were considered statistically significant.
| Results|| |
A total of 85 patients were included. ARF was found in 10 cases (11.8%). The distribution of tetanus cases and ARF is summarized in [Table 1]. The mean age was 52 ± 16 years and over 82% were male.
The main symptoms and signs at admission were trismus (68.2%), dysfagia (50.6%), neck stiffness (41.2%), fever (23.5%), and abdominal pain (21.2%). Oliguria was found in 2 cases (2.4%) as summarized in [Table 2].
The mean laboratory values at admission were: serum creatinine 1.0 ± 0.6 mg/dL, blood urea nitrogen (BUN) 38 ± 26 mg/dL, sodium 137 ± 13 mEq/L, potassium 3.8 ± 0.6 mEq/L, hemoglobin 12 ± 1.9 g/dL, hematocrit 35 ± 5.4%, white blood cells 9,725 ± 3,919/mm 3 , platelets 267,879 ± 121,650/mm 3 , AST 81 ± 120 IU/L, ALT 62 ± 98 IU/L.
The mean of maximum and minimum systolic blood pressure was 146 ± 23 mmHg and 101 ± 19 mmHg, respectively. The maximum and minimum diastolic blood pressure was 93 ± 14 mmHg and 61 ± 11 mmHg, respectively. The maximum and minimum heart rate was 103 ± 17 bpm and 66 ± 13 bpm.
Among the 10 patients with ARF in our study, serum creatinine ranged from 1.5 to 6.2 (2.56 ± 1.78 mg/dL) and BUN ranged from 39 to 136 (80.3 ± 33.7 mg/dL). The BUN/creatinine ratio ranged from 25 to 78 (38.7 ± 14.8). None of these patients had oliguria. Tachycardia and fluctuations in blood pressure were observed in these patients. Heart rate was 108 ± 15 bpm. The variation in systolic blood pressure was 59 ± 25 mmHg (30-100) and diastolic blood pressure was 36 ± 19 mmHg (20-80).
Death occurred in 8 cases (9.4%). Hyperglicemia (OR = 1.014, CI = 1.001-1.028, p = 0.03), hyperkalemia (OR = 3.2, CI = 1.0-10.4, p = 0.04), and thrombocytopenia (OR = 1.000, CI = 1.000-1.000, p = 0.03) were associated with increased mortality. ARF was not associated with an increased risk of death (p>0.5). [Table 3] shows a comparison between survivors and non survivor patients.
| Discussion|| |
Tetanus is an infectious disease that is preventable through vaccination but is still endemic in our region.  Neck stiffness and difficulty opening the mouth are usually early symptoms. Trismus is caused by a masseter spasm. A spasm progressively extends to other muscles, such as those of swallowing leading to dysphagia. , These common clinical signs and symptoms were also seen in over half of the patients in this study.
We found that hyperglycemia is associated with a greater risk of death. ARF was a complication found in almost 12% of patients, but did not show significant association with increased risk of death.
Among the patients who died (n=8), only one, a 23-year-old male, had ARF. His serum creatinine was 1.7 mg/dL and BUN was 75 mg/dl on admission. He also had sepsis with leukocytosis (12.700/mm 3 ), tachycardia (120 bpm), tachypnea (40 irmp), and a temperature of 39°C. He died 24 hours after admission. Thus, septicemia played an important role in the pathogenesis of renal dysfunction in this case. On the other hand, all patients who died had raised serum glucose, ranging from 105 to 259 mg/dL. As for lower values of serum sodium found in those who died, raised glucose may have contributed to that; serum sodium decreases by 1.9 mg/dL for every 100 mg/dL increase in glucose above normal.
Hypotension due to dehydration was not the cause of the acute renal failure, since adequate hydration was maintained in all patients. In the same way, nephrotoxic drugs and rhabdomyolysis were not observed to be involved with acute renal failure.in those patients.
Studies have shown that in severe tetanus impaired renal tubular function and decrease in glomerular filtration rate can occur. Sespis, dehydration, rhabdomyolysis, and alterations in renal blood flow due to catecholamines can contribute to renal failure. Clinically important renal impairment is associated with adrenergic overactivity and renal histology frequnetly shows acute tubular necrosis. ,,,
In summary, mortality was not high among the studied patients. Acute renal failure is an important complication of tetanus, but was not associated with death and this maybe due to prompt specific treatment. Hyperglicemia, hyperkalemia, and thrombocytopenia seem to increase mortality. Autonomic dysfunction seems to be an important pathophysiologic mechanism by which acute renal failure develops.
| Acknowledgement|| |
We are very grateful to the team of attending physicians, residents, medical students, and nurses from the Sao Jose Infectious Diseases Hospital for the assistance provided to the patients and for the technical support provided for the development of this research.
| References|| |
|1.||Veronesi R, Focaccia R, Tavares W, Mazza CC. Tιtano. In: Veronesi R, Focaccia R editors. Tratado de Infectologia. 2ª ediηγo. Sγo Paulo: Editora Atheneu; 2002. p. 909-35. |
|2.||Wilkins CA, Richter MB, Hobbs WB, Whitcomb M, Bergh N, Carstens J. Occurrence of Clostridium tetani in soil and horses. S Afr Med J 1988;73:718-20. [PUBMED] |
|3.||Pinder M. Controversies in the management of severe tetanus. Intensive Care Med 1997;14:129-43. |
|4.||Collingridge GL, Davies J. The in vitro inhibition of GABA release by tetanus toxin. Neuropharmacology 1982;21:851-5. [PUBMED] |
|5.||Curtis DR, De Groat WC. Tetanus toxin and spinal inhibition. Brain Res 1968;10:208-12. [PUBMED] [FULLTEXT]|
|6.||Curtis DR, Felix D, Game CJA, McCulloch RM. Tetanus toxin and the synaptic release of GABA. Brain Res 1973;51 358-62. |
|7.||Cook TM, Protheroe RT, Handel JM. Tetanus: A review of the literature. Br J Anaesth 2001;87:477-87. [PUBMED] [FULLTEXT]|
|8.||Sanford JP. Tetanus - forgotten but not gone. N Engl J Med 1995;332:812-3. [PUBMED] [FULLTEXT]|
|9.||Bleck TP. Tetanus: Dealing with the continuing clinical challenge. J Crit Ill 1987;2:41-52. |
|10.||Mallick IH, Winslet MC. A review of the epidemiology, pathogenesis and management of tetanus. Int J Surg 2004;2:109-12. [PUBMED] |
|11.||Seydi M, Soumare M, Gbangba-Ngai E, Ngadeu JF, Diop BM, N'diaye B, et al. Current aspects of pediatric and adult tetanus in Dakar. Med Mal Infect 2005;35:28-32. |
|12.||Soumare M, Seydi M, Ndour CT, Ndour JD, Diop BM. Epidemiology, clinical features and prognosis of juvenile tetanus in Dakar, Senegal. Bull Soc Pathol Exot 2005;98:371-3. |
|13.||Kokal KC, Dastur FD, Madashur AA, Kolhatkar VP. Disordered pulmonary function in tetanus. J Assoc Physicians India 1984;32:691-5. |
|14.||Corbett L, Spalding JM, Harris PJ. Hypotension in tetanus. Br Med J 1973;3:423-8. |
|15.||Sanya EO, Taiwo SS, Olarinoye JK, Aje A, Daramola OO, Ogunniyi A. A 12-year review of cases of adult tetanus managed at the University College Hospital, Ibadan, Nigeria. Trop Doct 2007;37:170-3. [PUBMED] [FULLTEXT]|
|16.||Brauner JS, Clausell N. Neurohumoral, immunoinflammatory and cardiovascular profile of patients with severe tetanus: A prospective study. J Negat Results Biomed 2006;5:2. [PUBMED] [FULLTEXT]|
|17.||Seedat YK, Omar MAK, Seedat MA, Wesley A, Pather M. Renal failure in tetanus. Br Med J (Clin Res Ed) 1981;282:360-1. |
|18.||Martinelli R. Matos CM, Roche H. Tetanus as a cause of acute renal failure: Possible role of rhabdomyolysis. Rev Soc Bras Med Trop 1993;26:14. |
|19.||Hilton R. Acute renal failure. BMJ 2006;333:786-90. [PUBMED] [FULLTEXT]|
|20.||Daher EF, Abdulkader RC, Motti E, Marcondes M, Sabbaga E, Burdmann EA. Prospective study of tetanus-induced acute renal dysfunction: Role of adrenergic overactivity. Am J Trop Med Hyg 1997;57:610-4. [PUBMED] [FULLTEXT]|
|21.||Wasay M, Khealani BA, Talati N, Shamsi R, Syed NA, Salahuddin N. Autonomic nervous system dysfunction predicts poor prognosis in patients with mild to moderate tetanus. BMC Neurol 2005;5:2. [PUBMED] [FULLTEXT]|
|22.||Gergen PJ, McQuillan GM, Kiely M, Ezzati-Rice TM, Sutter RW, Virella G. A population-based serologic survey of immunity to tetanus in the United States. N Engl J Med 1995;332:761-6. [PUBMED] [FULLTEXT]|
|23.||Pascual FB, McGinley EL, Zanardi LR, Cortese MM, Murphy TV. Tetanus surveillance-United States, 1998-2000. MMWR Surveill Summ 2003;52:1-8. |
|24.||Hesse IF, Mensah A, Asante DK, Lartey M, Neequaye A. Adult tetanus in Accra, why the high mortality? An audit of clinical management of tetanus. West Afr J Med 2005;24:157-61. |
|25.||Miranda Filho DB, Ximenes RA, Bernardino SN, Escariγo AG. Identification of risk factors for death from tetanus in Pernambuco, Brazil: A case-control study. Rev Inst Med Trop Sao Paulo 2000;42:333-9. |
|26.||Thwaites CL, Yen LM, Glover C, Tuan PQ, Nga NT, Parry J, et al. Predicting the clinical outcome of tetanus: The tetanus severity score. Trop Med Int Health 2006;11:279-87. [PUBMED] [FULLTEXT]|
|27.||Saltoglu N, Tasova Y, Midikli D, Burgut R, Dundar IH. Prognostic factors affecting deaths from adult tetanus. Clin Microbiol Infect 2004;10:229-33. |
|28.||Balmer P, Borrow R, Roper MH. The immunological basis for immunization series, Module 3: Tetanus. Update. Geneva: World Health Organization; 2007. |
|29.||Alfery DD, Rauscher A. Tetanus: A review. Crit Care Med 1979;4:176-81. |
|30.||Edmondson RS, Flowers MW. Intensive care in tetanus: Management, complications and mortality in 100 cases. Br Med J 1979;1:1401-4. [PUBMED] [FULLTEXT]|
|31.||Hariparsad D, Pather M, Rocke DA, Wesley AG. Renal function in tetanus. Intensive Care Med 1984;10:67-70. [PUBMED] |
|32.||Kerr JH, Corbett JL, Prys-Roberts C, Crampton Smith A, Spalding JMK. Involvement of the sympathetic nervous system in tetanus: Studies on 82 patients. Lancet 1968;2:236-41. |
Elizabeth F Daher
Rua Vicente Linhares, 1198 Fortaleza, CE, Brazil CEP: 60270-135
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2], [Table 3]