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
CNS Circ Hem Resp Ren HD
+
0
+
0
++++ 4
++++ ++++ ++++ ++++ ++++ 1
+
+
++++ 0
++++ 4
0
0
+
0
++++ 4
+
0
0
0
++ 0
++++ ++++ ++ ++++ ++++ 10
++++ ++++ ++++ ++++ ++++ 1
+
+
++
0
++++ 4
+
+
++++ 0
++++ 0
0
+
0
0
++++ 3
Outcome
Liv
S.D. 21
1992
+
recovery
Š.V. 40
1992
+++ died
J.M. 21
1992
0
recovery
R.D 24
1992
+
recovery
G.M 35
1993
+
recovery
D.G. 25
1995
++++ died
B.A. 32
1995
++++ died
K.T. 31
1995
+
recover
M.Z. 32
1995
+
recovery
V.V. 29
1995
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 19921995 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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liver in patients with epidemic haemorrhagic fever. Chug-Hua Nei Ko Tsa Chin
Chin Chin J Int Med 1992:31:95-97.
2) Huang YX, dong J, Lu QY. A study on gastric mucosa damage, antigen location
and virus dissociation in patients with epidemic haemorrhagic fever, ibid.
1993;32:726-728.
3) Shen KQ. Detection of haemorrhagic fever virus RNA in renal tissue and
peripheral blood in patients with haemorrhagic fever with renal syndrome. Chung
Hua and Hsuch Tsa Chin Chin Med J 1993;73:609-611.
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glycoproteins sby monoclonal antibodies in renal tissue from patients with Korean
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Hantaan virus-related structures in kidnies of cadavers with haemorrhagic fever
with renal syndrome. Arch Virol 1992;122:187-194.
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strain of Hantaan virus from fatal case of hemorrhagic fever with renal syndrome.
Am J Trop Med Hyg 1994; 51:393-400.
7) Khan AS, Ksiazek TG, Peters CJ, Hantavirus pulmonary syndrome. Lancet
1996;347:739-741.
8) Marshall JC, Cook DJ, Sibbad WS, Roy PD, Cristou NV.The multiple organ
dysfunction (MOD) score: a reliable descriptor of a complex clinical outcome.
Crit Care Med 1992;20:S80 (Abstract).
9) Gašparović V, Radonić R, Gjurašin M et al. Acute renal failure in the war in
Croatia. World Congress of Nephrology, Jerusalem, 1993.