Hydroxyethyl starch does not cross the blood-brain or the placental barrier but the perineurium of peripheral nerves in infused animals

Abstract

Therapy with hydroxyethyl starch (HES) is associated with a high incidence of persistent pruritus due to HES storage in cutaneous nerves. Up to now it has been unknown if HES also accumulates in the extracutaneous peripheral or central nervous system. To study this, five rats including one pregnant one were infused with a single dose (34-150 mg) of HES (70/200/450 kDa molecular weight) conjugated with fluorescein isothiocyanate (FITC). In addition, four sheep were infused with a cumulative dosage of 30 g, 120 g, and 420 g HES (200 kDa), respectively. After 7-13 days, biopsies from the adult rats, four fetal rats and sheep were taken from various organs. The specimens were analyzed by light, electron, and confocal laser scanning microscopy. Typical HES storage vacuoles were found in macrophages of the skin, liver, spleen, lung, and kidney. HES storage in healthy animals was not associated with signs of either inflammation or apoptosis contrary to a previously described animal hemorrhagic shock model. Beyond that, fetus biopsies did not show any storage phenomenon, confirming that HES does not cross the placental barrier. Deposits of HES could be detected in Schwann cells of cutaneous nerve fibers as well as in perineural and endoneural cells of sciatic nerve in one rat (HES 450 kDa) and three of four sheep. No HES storage was found in the central nervous system. Our findings clearly demonstrate that storage of HES is detectable only in small peripheral nerves, suggesting a cutaneous origin of the HES-induced pruritus.

Quality of life and pruritus in patients with severe sepsis resuscitated with hydroxyethyl starch long-term follow-up of a randomised trial

“…In addition, long-term toxic effects of HES deposited in kidney, liver and bone marrow have been documented [22-25]. HES does not seem to cross the intact blood-brain barrier in animal models, however, it does accumulate in the peripheral nerves [26,27]. These toxic effects may affect the general health and thereby HRQoL of the patients, but we do not have data to substantiate such effects in our patients.…”

Blood volume determination in obese and normal-weight gravidas: the hydroxyethyl starch method

“…21, 33-36 The HES method for blood volume estimation is a rapid, safe, and acceptable technique for use in pregnant patients, and does not cross the placenta. 32,33,37,38 …”

Epidural hydroxyethyl starch ameliorating postdural puncture headache after accidental dural puncture

“…Experimental studies indicated that HES has a positive role in improving microcirculation and attenuating inflammation [34,35] . A previous rat and sheep study reported that with HES (450 kD) infusion, HES storage vacuoles were typically detectable in macrophages of small peripheral nerves in the skin, liver, lung, and kidney, and were not associated with signs of either inflammation or apoptosis [36] . Deposits of HES could be detected in perineural and endoneural cells of sciatic nerve.…”

“…[ 34 , 35 ] A previous rat and sheep study reported that with HES (450 kD) infusion, HES storage vacuoles were typically detectable in macrophages of small peripheral nerves in the skin, liver, lung, and kidney, and were not associated with signs of either inflammation or apoptosis. [ 36 ] Deposits of HES could be detected in perineural and endoneural cells of sciatic nerve. A study evaluating pruritus following various cumulative dosages of HES infusion in 93 patients revealed that dose-dependent HES-reactive vacuoles could be demonstrated in the Schwann cells of unmyelinated, as well as small myelinated, nerve fibers, and endoneural and perineural cells in the skin.…”