Pulmonary involvement. A new pattern of the severe clinical picture in patients with haemorrhagic fever with renal syndrome?
Ivanović D., Radonić R., Gašparović V., Merkler M., Gjurašin M.,
Department of Medicine
Division of Emergency and Intensive Care Medicine
University Hospital Centre, Zagreb, Croatia
SUMMARY
In our country haemorrhagic fever with renal syndrome (HFRS) was a sporadic disease with low mortality rate. During 4 years period (1992-1995) 10 patients, all male, mean age 29 years (21-40) were admitted to our intensive care unit (ICU) with serologically confirmed HFRS. All patients but one had an acute renal failure necessitating haemodialysis. Three patients died (MODS score 21-24). One patient died in 1992 because of intractable shock with marked systolic dysfunction of the heart. Two patients died in 1995. Both had severe pulmonary heamorrhages which caused respiratory insufficiency. There is a question whether is it a possibility of an evolving changing pattern of HFRS in our contry.
INTRODUCTIONS
Hemorrhagic fever with renal syndrome (HFRS) is an acute ineffective disease characterised by fever, capillary lesions with leakage of blood, leading to haemorrhagic manifestations and organ dysfunction with acute renal failure as the most prominent feature. The disease is caused by several closely related viruses of the genus Hantavirus, family Bunyviridae. The virus is transmitted from rodents, which serve as reservoirs in endemic areas. The rodents wxcrete virus in urine, saliva and faeces. Subject at risk are those in close contact with rodents and their excreta, such as soldiers, compers and farmers. The basic pathoanatomical substrate is small blood vessel lesion with haemorrhagic exudation. Presence of the viruses has been demonstrated in cells of many organs, especially in renal tubule cells (1-6). The disease manifestations varies in severity. It is mostly mild or moderate, characterised by fever, facial flush, muscle pain, petechial haemorrhages and renal failure with proteinuria. Some patients have an extremely severe picture, with the development of deep, intractable shock with high risk of lethal outcome in spite of treatment. There are reports (7) about the disease caused by Hantaan virus in North America, where pulmonary involvement is the leading feature, only uncommonly associated with renal failure.
PATIENTS AND METHODS
In the 1992-1995. period, ten patients with serologically or patoanatomically verified HFRS were treated in our ICU. Four patients more had a characteristic clinical picture of HFRS, but the diagnosis was not serologically confirmed. All HFRS patients were males most of them soldiers who had stayed at the battlefield, with possible close contact with small rodents. Most of them were transferred in our ICU from other institutions because of the renal failure and the needs for the hemodialysis in addition to other intensive care procedures. All patients had a severe from of the disease, with a failure of one or more organ systems. We have used Marshall’s multiple organe dysfunction (MOD) score criteria (8) for the assessment of the severity of the disease in our patients.
RESULTS
Table 1 shows the date of the patients with HFRS treated in our ICU. All patients had renal failure. Only in one patient, renal function recovered before the introduction of hemodialysis. In other 1-10 hemodialysis sessions were carried out. Five of ten patients had pronounced thrombocitopenia. Platelet replacement was indicated in four patients, due to platelet count decline to less than 25000. Most patients had milde hepatic lesion, detected by a slight increase of serum transaminases. Most patients had dysfunction of the gut, characterised by nausea, anorexia, transitory food intolerance or fleeding form GI tract. Three patients died.On of them died within a few hours because of profund shock. Beside intravascular deficit, pronounced systolic dysfunction of the myocardium was verified by bedside echocardiography. In another patient, a fully developed multiple organ failure syndrome was associated with deep coma, hepatic insufficiency, (PT 14%, bilirubin, 243 mmol/L, AST 243 mmol/L, ALT 160 mmol/L, gama GT 479 mmol/L), respiratory insufficiency, bleeding from the gastrointestinal tract, while renal failure required 10 hemodialysis sessions. The cause of death was intractable haemorrhage from the airways which compromised ventilation. Pseudomonas aeruginosa was isolated from the tracheal aspirate. On autopsy, numerous blood tamponades were detected in the small airways. The similar, but shorter course of the disease was recorded in the third patient who died in acute intractable respiratory insufficiency due to bronchial obstruction by blood.
Table 1
Patients with HFRS treated from 1992-1995 at the ICU, Department of Medicine, University Hospital Centre Zagreb, Croatia
Patient Age Year. Organ system dysfunction Outcome
CNS Circ Hem Resp Ren HD Liv
S.D. 21 1992 + 0 + 0 ++++ 4 + recovery
Š.V. 40 1992 ++++ ++++ ++++ ++++ ++++ 1 +++ died
J.M. 21 1992 + + ++++ 0 ++++ 4 0 recovery
R.D 24 1992 0 0 + 0 ++++ 4 + recovery
G.M 35 1993 + 0 0 0 ++ 0 + recovery
D.G. 25 1995 ++++ ++++ ++ ++++ ++++ 10 ++++ died
B.A. 32 1995 ++++ ++++ ++++ ++++ ++++ 1 ++++ died
K.T. 31 1995 + + ++ 0 ++++ 4 + recover
M.Z. 32 1995 + + ++++ 0 ++++ 0 + recovery
V.V. 29 1995 0 + 0 0 ++++ 3 0 recovery
______
CNS =central nervous system; Circ = circulatory system; Hem = hematologic system;
Resp=respiratory system; Ren=renal system; HD=number of hemodialysis sessions; Liv=liver
DISCUSSION
According to the data obtained from Croatian Institute of Public health form 1992-1995 there was 147 reported cases of HFRS with extremely large number (124 patients) in year 1995. The increasing frequency of the disease could at least in part be explained by was actions (9). Of them ten patients with severe course of the disease were transferred to our unit. All of them but one had renal insufficiency necessitating hemodialysis. Two of three patients who died had prominent pulmonary haemorrhage which compromised respiration and were the immediate cause of death. By our experiences it was an unusual complication which differ from classical clinical picture. It is known that respiratory superinfections could complicate the course of the disease. We have documented Pseudomonas superinfection in one patient, and it is possible that this contributed to the development of the severe multiple organ failure. But, still it could not explain the respiratory haemorrhage. There are reported cases of Hantaan virus infection in North America with pulmonary involvement as the leading manifestation of the disease, realy associated with concomitant renal affection, which differs from classical clinical picture of HFRS. Extravasation of fluid but not blood is the pathoanatomic substrate (7).
It is an intriguing question weather such course of the disease in our patients could be due to changes in viral nature, or there are other explanation of that. Further observations and studies are needed to solve that question.
LITERATURE:
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9) Gašparović V, Radonić R, Gjurašin M et al. Acute renal failure in the war in Croatia. World Congress of Nephrology, Jerusalem, 1993.