Artificial Cells, Blood Substitutes, and Biotechnology

ISSN: 1073-1199 (Print) 1532-4184 (Online) Journal homepage: https://www.tandfonline.com/loi/ianb19

Clinical Results of Perftoran Application: Present

and Future

Eugene Maevsky, Genrih Ivanitsky, Ludmila Bogdanova, Olga Axenova,

Natalia Karmen, Eugene Zhiburt, Raisa Senina, Sergey Pushkin, Igor
Maslennikov, Andrey Orlov & Irina Marinicheva

To cite this article: Eugene Maevsky, Genrih Ivanitsky, Ludmila Bogdanova, Olga Axenova,
Natalia Karmen, Eugene Zhiburt, Raisa Senina, Sergey Pushkin, Igor Maslennikov, Andrey Orlov
& Irina Marinicheva (2005) Clinical Results of Perftoran Application: Present and Future, Artificial
Cells, Blood Substitutes, and Biotechnology, 33:1, 37-46, DOI: 10.1081/BIO-200046654

To link to this article: https://doi.org/10.1081/BIO-200046654

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Artificial Cells, Blood Substitutes, and Biotechnology, 33: 37–46, 2005
Copyright Q Taylor & Francis, Inc.
ISSN: 1073-1199 print/1532-4184 online
DOI: 10.1081/BIO-200046654

Clinical Results of Perftoran Application:

Present and Future

Eugene Maevsky, Genrih Ivanitsky, Ludmila Bogdanova, Olga

Axenova, and Natalia Karmen
Institute of Theoretical and Experimental Biophysics of RAS,
Moscow Region, Russia

Eugene Zhiburt
Center of Industrial Transfusiology of Russian Ministry of
Health, Moscow, Russia

Raisa Senina, Sergey Pushkin, and Igor Maslennikov

OA Scientific-Productive Company Perftoran,
Moscow Region, Russia

Andrey Orlov and Irina Marinicheva

Central Scientific-Research Institute of Stomatology,
Moscow, Russia

Abstract: Clinical experience of Perftoran (commercial drug of low concentrated

perfluorocheminal emulsion) applications is presented in some statistical data and
in brief analysis of clinical trials and following clinical studies described in the
Russian scientific literature. Observed data allow us to suppose that Perftoran
facilitates oxygen delivery together with remaining red blood cells at blood
replacements and will have more wider area for application than just a blood
substitute. Its infusion alleviates symptoms of ischemia at different types of
occlusion vessels disease, improves grafting in plastic surgery, diminishes inflam-
mation and prevents rejection of transplants, activates detoxication functions of
liver, inhibits retro-virus infection development. Local PF applications is able
to accelerate wounds and ulcers healing.

We thank T. N. Kharybina and her colleagues in Pushchino Library, Professor

G. A. Sofronov and his coworkers from the Military Medical Academy in Saint-
Petersburg for their help in looking for information about Perftoran applications.
Address correspondence to Eugene Maevsky, Institute of Theoretical and
Experimental Biophysics of RAS, 142290, Pushchino, Institutskaya, 3, Moscow
Region, Russia. E-mail: emaevsky@iteb.ru

37
38 E. Maevsky et al.

Keywords: Perftoran, review clinical usage

1. GENERAL PICTURE OF PERFTORAN APPLICATION

This paper presents a generalization of the widely used clinical appli-

cation of Perftoran (PF). PF contains 10 vol.% perfluorochemicals
(PFCs): perfluorodecalin and perfluoro-N-(4-methylcyclohexyl)-
piperidine in ratio 7:3 emulsified by non ionic surfactant Proxanol-268
in an isotonic electrolyte solution with average emulsion particle size of
about 0.07 mm (Table 1).
The whole composition of PF is packed in one bottle and has to be
stored either frozen (at
18C to
4C for 3 years) or under refrigeration
(at 4C for 2 weeks). PF is manufactured by Scientific-Productive Com-
pany ‘‘Perftoran.’’ PF was registered in Russia in 1996 as an oxygen-
carrying blood substitute. The various opportunities of PF applications
(and not only for blood replacement) have already been revealed on the
basis of analysis of patients distribution (Table 2) during preregistration
clinical trials [1–4].
As is shown in Table 2, PF was administered in dosages from 4 to
30 ml=kg depending on the disease. The largest summary doses were from
1000 to 5300 ml for the treatment of severe anemia.
In 1997, Scientific-Productive Company ‘‘Perftoran’’ began to sell
PF to Central Regional Stations of Blood Transfusion and different hos-
pitals. Judging the volume of the wholesale and assuming that a single
patient received about 1000 ml, we deduced that PF had been adminis-
tered to about 4500 patients. Information about PF use was collected

Table 1. Perftoran composition and its physical-chemical properties

F-decalin and its satellites 7.0 ml
F—N-(4-methylcyclohexyl)-piperidine and its satellites 3.0 ml
Proxanol-268 4.0 g
NaCl 0.6 g
KCl 0.039 g
MgCl2 0.019 g
NaHCO3 0.065 g
NaH2PO4 0.02 g
Glucose 0.2 g
H2O to 100 ml
[F
] 10 mM
Osmotic pressure 300 mOsM
pH 7.3
Viscosity 2.3 cP
Clinical Results of Perftoran Application 39

Table 2. Distribution of patients according to indications during clinical trials

Doses, Summary Patients % side

Indications ml per kg BW doses, L distributions reactions

1. Acute blood loss and 6–30 1.0–5.0 23.5% 2%

hemorrhagic shock
2. Polytrauma, cranial- 4–12 0.4–1.2 20% 0%
cerebral trauma, shock
3. Toxic-infection shock 4–8 0.4–1.0 12,7% 0%
4. Occlusion of blood vessels 4–6 0.4–0.8 20,7% 20%
and acute heart infarct
5. Cardioplegia – 1.0–2.0 11.1% 0%
6. Transplantation 30 1.0–2.0 4,8% 0%
7. Burns, oncology & others 2–8 0.1–1.0 8.2% 25%
Total 912 patients 100% 6,9%

with the help of questionnaires from 21 regions of Russia. The answers of

respondents gave total evaluation of PF efficiency, which looked as fol-
lows: positive effects
88,3%, negative effects
3,3%, absence of any
effect
8,3%; different side effects were listed in 4% of cases.
Analysis of the Russian scientific literature from 1997 to 2002 let us
find a listing of 1823 patients treated with PF in comparative studies with
a total of 3332 patients (Table 3). The new fields of PF usage in clinical
practice are much wider than was found out during clinical trials. Almost

Table 3. Indications and distribution of patients treated with Perftoran in com-

parative studies listed in Russia scientific literature for the period up to 2002

Total 3332= Distribution of

Perftoran patients with
Indications treated 1823 Perftoran

1. Blood losses, multiple organ failure 862=401 22.0%

2. Disorders of perfusion and 490=292 16.02
microcirculation (without blood loss)
3. Dysfunction of inflammatory response 269=163 8.9%
4. Detoxication 375=170 9.3%
5. Lung function damage, RDSA 197=152 8.3%
6. Cranial-cerebral trauma 184=134 7.3%
7. Burns, thermal shock 123=53 2.9%
8. Transplantation 206=87 4.8%
9. Cardioplegia, cardiopulmonary bypass 165=72 3.9%
10. Local application: wound & ulcer of 461=299 16.2%
mucous, skin, spinal cord
40 E. Maevsky et al.

the complete reference list of PF applications for the period up to 2001

was published in Russian by G.A. Sofronov et al. [5].

2. THE PLACE OF PERFTORAN IN INFUSION-TRANSFUSION

THERAPY OF BLOOD LOSSES

According to the initial conception, PF was developed and manu-

factured as a blood substitute. Correspondingly, Perftoran should have
been used in lieu of allogeneic blood and banked red blood cells (RBC)
during the substitution of massive blood losses (about 1000–2500 ml). At
massive blood replacement PF was used together with a combination of
plasma expanders (dextran 60 or hydroxyethylstarch was infused into
other veins or immediately after PF into the same vessel). Simul-
taneously it was necessary to provide the patients with breathing of
air enriched with supplementary O2. In these cases PF was used without
pure oxygen for breathing when the fraction of O2 in air did not exceed
0.4–0.6 [1–3, 6–9]. It enabled us to maintain venous pO2 at the level of
45–65 mm Hg and did not block HbO2 desaturation in the remaining
erythrocytes.
Analysis of PF usage at massive, moderate and small blood losses has
shown that PF was able to significantly improve tissue oxygenation due
to oxygen delivery together with the remaining RBC and to facilitate
blood rheology at early stages of infusion-transfusion therapy. PF turned
out to be useful even if the level of circulating erythrocytes and hemoglo-
bin was still sufficient (did not reach the trigger level of blood trans-
fusion) and there was no need to use banked donor blood or RBCs
[10–12]. Consequently, a conclusion was made that PF should be
administered at early stages of blood loss treatment immediately after
crystalloid solutions (Table 4) when the symptoms of hypoxia, ischemia
and microcirculation disorders appeared.
The basic results of Perftoran application at blood replacement were
an increase in efficiency of reanimation treatment and shortening of rean-
imation period, duration of lung artificial ventilation, an improvement of
oxygen transport and its consumption, a decrease in the demand in banked
blood and blood components more than 2-fold and even avoidance of
donor blood infusion [1–3, 6–9]. Side reactions such as hypotension and
pulmonary complications were observed at massive blood replacement
with PF in about 1% of cases. The stomach-duodenal bleeding and oper-
ation blood losses are good examples when PF provided maintenance of
arterial PO2 on the higher level than crystalloids or colloids [6–12]. In com-
parison with dextran 60 Perftoran decreased more efficiently heart rate,
blood viscosity and erythrocytes rigidity, augmented the arterial pressure,
cardiac output and central venous pressure, maintained vessel resistance
 Table 4. The place of perftoran in infusion-transfusion therapy of blood losses

Blood loss volume Transfusion means and doses (ml)

% Circulat. Fresh Red blood

Blood frozen cells
ml Volume Crystalloids Perftoran Colloids Albumin 10% plasma & platelets

< 750 <15 1500 200–300 – – – –

750–1500 15–30 1500–2000 500–700 600–800 – – –
1500–2000 30–40 1000–1500 800–1000 800 –1200 100–200 1000–1500 on indications
>2000 >40 800–1000 1000–1500 1200–1500 200–300 1500–2000 2–6 units

41
42 E. Maevsky et al.

and circulating blood volume. Thanks to that, Perftoran diminished aci-

dosis. Here it is necessary to mention that in most cases the positive effect
of PF was reached after its usage in small doses of 4–6 ml per kg body
weight when the supplementary oxygen capacity of PFC emulsion was
insignificant. These doses of PF accelerated patients’ resuscitation after
cranial-cerebral trauma [12] and burns shock [9].
Significant antiacidosis effect and improvement of tissue oxygenation
were obtained within cardiopulmonary bypass with PF during recon-
struction operation on heart in more than 45 patients [13].

3. PERFTORAN IMPROVES TISSUE OXYGENATION AT THE

TREATMENT OF OCCLUSIVE VESSELS DAMAGES

V. Moroz et al. [1,2] obtained 30% of skin PO2 augmentation measured

with transcutaneal device after infusion of 400 ml of PF, while dextran
40 gave only 6% of tissue PO2 increase. Ultrasound dopplerometry
and thermovision images demonstrated an improved resuscitation of
the blood flow immediately after infusion of 200 ml PF. Summary effects
received on 92 patients in the Rehabilitation Center of Government
Medical Department are shown in Table 5. Treatment with repeated
Perftoran infusion eliminated pain at rest and significantly enhanced
painfree distances.
L. V. Usenko et al. [14] and later a number of other researchers [15],
described the diminishing of necrotic region after heart infarct treated
with very small doses of PF: 100 ml per infusion.

4. IN TRANSPLANTOLOGY PF DECREASED KIDNEY GRAFTS

REJECTION 2-FOLD

Infusion of 1000–2000 ml of PF into kidney cadaver donors who had no

heart function alleviated symptoms of kidney ischemia and decreased

TABLE 5. Results of Perftoran treatment at the occlusive vessels diseases of legs

(Rehabilitation Center of Government Medical Department, 1999–2002)

Quantity &
average age Painfree distances, Pains Stages of
of patients Treatment m (% of patients) at rest diseases

before Perftoran  180 (100%) 50% 2–3b

N ¼ 92 Perftoran 200 ml  2–3 1200 750 200 0 1–2a
every 6–9 months
68 years (87%) (9%) (4%)
Clinical Results of Perftoran Application 43

graft reperfusion injury. Reperfusion damages and graft rejections dimin-

ished also after infusion of PF in dosage of 4–6 ml per kg body weight
into recipients after transplantation [16,17].

5. UNEXPECTED PERFTORAN APPLICATIONS

A. The first clinical experience of PF application for detoxication aim has

been recently presented at the treatment of poisoning with carbofos
and psyhotropic drugs [18]. PF usage was based on its capabilities
to sorb lipophylic substances in blood stream and to induce the syn-
thesis de novo of cytochrom P450 in liver [19].
B. Taking into account the fact that PF is able to inhibit functions of
hyperactivated macrophages and primed neutrophils [20], which can
produce viral particles and a lot of cytotoxic products, an attempt
was made to treat 14 patients infected by human immunodeficiency
virus (HIV) and suffered the last 2–3 years from secondary infections,
weakness, tiredness, body weight loss, and in-ability to work [21].
After PF courses, which included several intravenous infusions, 12
patients felt much better, could return to work, stopped losing weight.
Two patients did not undergo PF treatment because of side reactions.
Within the year of treatment with PF, the secondary infections did not
manifest. No significant changes in blood analysis were found except
for some shifts in concentrations of HIV-1 and p24 protein in blood.
C. An antiinflammatory effect of PF infusions applied at chronic uveitis
of different etiology was obtained in the Center of Eye Microsurgery
in Moscow [22]. A stable recovery was found after supplementary PF
infusions (100 ml two times only) in 39 patients out of 40 in cases when
previous traditional treatment did not produce any positive effect. PF
infusion has been stopped in 1 case because of a side reaction after the
first 5 drops of PF. Blood analysis revealed that concentrations of cir-
culating immune complexes and CD-4 lymphacytes in this patient’s
blood had an unusual response to PF.
D. Original data were submitted by neurosurgeon Pavel Katunyan from
Moscow Medical Academy [23]. He used oxygenated PF for local lavage
of injured spinal cord at the decompression operation and simul-
taneously administered 200 ml of PF intravenously. Additionally,
5–6 intravenous infusions were made in the post–operation period.
When PF was administered during the first days after trauma, the
elastase activity of neutrophils in peripheric blood of patients
dropped and this phenomenon was accompanied by the improve-
ment of neorulogic state within 3 months. But delayed PF appli-
cation or traditional therapy either slightly improved neurologic
state or did not produce any improvement at all.
44 E. Maevsky et al.

E. Acceleration of healing was shown after PF lavage and local PF

applications on the surface of stomach ulcer, skin wounds and even
on leprosy chronic ulcers [24,25].

CONCLUSION

The data described in the Russian scientific literature seem to show the
place of PF among other blood substitutes as an antihypoxic and anti-
ishemic drug that is worth administering on early stages of blood loss
as it improves the functions of the remaining RBC, and thanks to that
increases tissue oxygenation, delays usage of donor RBC and decreases
demand in banked blood. Analyzed clinical experience enables us to
suppose that, thanks to its various biophysical properties, PF will have
a wider area of application than just as a blood substitute. Its infusion
alleviates symptoms of ischemia in different types of occlusion vessels
diseases, improves grafting in plastic surgery, diminishes inflammation
and prevents rejection of transplan, activates detoxication functions of
liver, and inhibits retrovirus infection development. Local PF application
is able to accelerate wound and ulcer healing.

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