Introduction and publications review

Reduction of the in-surgery blood loss is currently regarded as one of the most easily
available and indicative criteria of the reduced surgical injury rate. Minimum invasive
treatments allowing the reduce blood loss through the use of special technical means
(retractor systems, video equipment, etc.) are not available at all clinics and are quite
expensive. Currently, there has been an active search in progress for local hemostatic
agents that could be used in various surgery fields, combining clinical efficacy with
affordability and relatively low cost. Most hemostatic materials intended for local
application (hemostatic sponges, powders, adhesives, including Surgiflo, Surgicel etc.),
despite their high effectiveness, are impossible to use in case of large wound surface. At
the same time, the market value of the most common local hemostatic materials varies
considerably: sponges - from 3400 to 14548 rubles per item (1), hemostatic fleece with
thrombin - from 13 268.2 to 24 378.2 rubles per 1 bottle (2, 3), and surgical adhesive with
its preparation kit - 11 700 rubles per item. Partial polyacrylic acid silver salt is one of the hemostatic substances that is affordable for healthcare institutions in terms of its efficiency and cost ratio, and the agents of which are permitted for application abroad and in Russia. Research and clinical experience of its application is limited to activities in the field of general (abdominal) surgery, there are occasional publications in the field of Ophthalmology, Obstetrics & Gynaecology (5-7), at that, the nature of the active ingredient of the agent, in addition to the main (hemostatic) one, also provides for a bactericidal and bacteriostatic effect due to silver ion content. The agent's action pattern consists of several successive stages: initially, the active ingredient binds to blood plasma proteins (primarily albumin), forming a polyacrylic matrix structure containing albumin molecules in the polyacrylic matrix cells. This structure creates several layers on the surface of the wound, and silver ions are recovered and produce a bactericidal effect. The polyacrylic matrix is then plasmolyzed, being substituted by fibrin. At the same time, the simplicity of use of the agent, which is applied to the wound surface by means of drapes moistened with a solution, and does not require precise dosing, as well as its safety, allow to expect a positive effect when used for spinal surgery, especially during interventions involving large traumatic approaches.

Study objective

Identifying the possible effect of the partial polyacrylic acid silver salt on the volume of in- and post-surgery blood loss during spinal surgeries performed via posterior instrumentation approach with the fixation of up to 3 segments.

Methods

A prospective, randomized multicenter study was conducted on the basis of three
clinical sites: National Medical Research Centre for Traumatology and Orthopaedics named after N.N.Priorov, Health Ministry of the Russian Federation.
- at the clinical sites of the Department of Traumatology, Orthopedics and Disaster
Surgery, FSAEI the First Moscow State Medical University named after I.M. Sechenov
Ministry of Health of Russia (Sechenov University), - State Budgetary Healtcare Institution of the City of Moscow "N.V. Sklifosovsky Federal Research Institute of Emergency Medicine of the Healthcare Department of the City of Moscow".
The study contains data about 180 patients aged 20 to 80, meeting the following
criteria: process distribution: from L1 to S1 inclusive multilevel (at least 3 segments) stenosis of spinal canal in case of degenerative scoliosis or vertebral fracture;
performance of decompressive surgery via posterior instrumentation approach,
requiring skeletization of neural archs of vertebrae and instrumental fixation of 1 to 3
spinal motion segments. The following were criteria for exclusion from the study:
co-existing chronic infectious disease or tumors;
divergence of one or several parameters of the coagulogram - prothrombin time,
prothrombin index Quick's vaue, , APPT, fibrinogen.
All the patients were divided into two equal groups (main and reference) of 90
people each, while each of the three centers studied equal number of patients (60 persons - 30 in the reference group and 30 in the main group). The main group included 30 consecutively operated patients who met the inclusion criteria, without regard to gender: in aggregate, it included 53 (58,8%) males and 37 (41,2%) females. The reference group was composed based on the gender-stratification randomization principle with a consistent enrollment of an equal number of patients — 15 males (50.0%) and 15 females (50.0%) at each center. The inclusion of data from 3 medical centers into the study ensured the comparability of the main and reference groups in terms of planned (degenerative stenosis) and emergency (spinal injury) surgeries
The clinical phase of the study completed after the treatment of 30 patients of the
reference group in each of the 3 centers. All the study participants gave their informed
voluntary consent to participate.
All the patients were operated on by the surgeons with experience in performing
decompressive spine surgeries ranging from 12 to 25 years. In the course of each
intervention during the spine and roots decompression there was performed exsection of
osseous structures in the volume of hemilaminectomy or interlaminectomy at the same
level. Intraoperative blood loss level was measured by collecting the drained blood with a
separate vacuum aspirator. Solutions for bathing the surgical wound were collected

separately. After accessing the spine and achieving sustained hemostasis of the wound
walls, aspirated blood was also collected in a separate container for the duration of the
spinal canal decompression. Thanks to this, the volume of blood lost during local bleeding
from bone tissue and Batson's epidural venous plexus was recorded as not included into the "scope of application" of the studied agent. During the treatment of the osseous structures and the spinal canal, the hemostasis was carried out by applying bipolar coagulation and bone wax. Sell-saver, allowing to automatically register the volume of collected (drained) blood, was used only occasionally (13 patients, or 7.22% of the total) due to the insignificant (less than 1 l.) expected volume of VBC losses and the availability of agents for blood substitution (both auto- and donor). During surgical interventions, the blood substitution was performed according to indications, though it did not exceed 1 dose (300 ml) of erythrocyte concentrate, and 2 doses (600 ml) of fresh frozen plasma (auto- or donor). Thus, the total blood loss being evaluated during the study, refers to diffuse muscular bleeding that occurred during the stages of accessing and suturing of wound, which in all cases was performed leaving wound drainage, used to evaluate the postoperative blood loss level. Reduction in daily blood loss to ….. /day was regarded as an indication for the wound drainage removal.
The major difference between the main and reference group was in the application of
the partial polyacrylic acid silver salt agent according to the following procedure:
during the skeletization of the vertebrae arches, a drape moistened (indicate the
solution dosage) of a solution of partial polyacrylic acid silver salt with an exposure time
of 2 to 5 minutes (the exposure duration was estimated visually by the nature of diffuse
bleeding) was placed on the wound surface. The same method was used for applying the
agent for the second time before suturing the wound; for the patients from the reference group, at the same surgery stages, hemostasis was carried out by means of a hemostatic sponge and drapes moistened with 3% hydrogen peroxide solution.
In both groups, mono- and bipolar electrocoagulation was applied at different stages
of the intervention. Statistical data analysis was performed using IBM SPSS Statistics 22 software. Methods of descriptive statistics were used to characterize the groups (main and reference), the groups comparison was performed using the Student's t-test. The p = 0.05 was used as a threshold level of significance.

Results

Data on the evaluated blood loss in patients of the main and reference groups is
shown in Table 1. Statistical analysis of the data in the table allows to define that the volume of operational blood loss (M ± σ, ml) in the experimental group was 258.1 ± 164.5 ml (min 90; max 890), in the reference group - 405.5 ± 157.9 ( min 190; max 950). In its turn, the drain blood loss during the postoperative period (M ± σ, ml) was 81.50 ± 77.046 (min 20; max 400) in the experimental group, and 151.56 ± 74.745 (min 20; max 600) in the
reference group. When comparing both intraoperative and postoperative blood loss,
statistically significant differences were obtained by Student's t-test (p <0.05), which makes it possible to make a conclusion about the effectiveness of the agent.

Table 1

Discussion

Currently, in the 'classical' orthopedics there is no a fully formulated need for new hemostatic agents. This is partly due to the fact that preference is given to the low-impact surgical approaches, in which case the surgery, especially scheduled one, is accompanied by minimal blood loss, often compensated by the body's reserves in the absolute majority of patients. Among the exceptions there are surgical treatments of significant damages, accompanied by a significant loss of VBC. Due to this reason, many orthopedic traumatologists do not consider elevant the special use of additional hemostatic agents, with the exception of the colleagues performing operations with estimated significant blood loss (e.g. total endoprosthesis replacement of large joints of the skeleton). The contemporary publications do not cover the issue of the use of the partial polyacrylic acid silver salt agent (PPA SS) in traumatology and orthopedics. Informational search using such keywords as 'traumatology','orthopedics', 'endoprosthetics', 'acute trauma' and other terms, as well as the name of the agent, returned no results. At the same time, information about the use of the agent in other areas of surgery, primarily in abdominal, is quite optimistic: Polyantsev et al. according to the data of the first use of PPA SS with endoscopic hemostasis in 20 patients aged 25-67, showed that only 3 patients had a bleeding relapse. No postoperative complications, except mentioned relapses, were registered; Andreyev et al. (10) obtained a persistent hemostatic effect in 23 of 26 patients (88.5%) with acute calculous cholecystitis and acute adhesive intestinal obstruction. Repeated 4-minute exposure of the agent was effectively used in 2 of 3 patients with relapsed bleeding, for 1 patient there was required a repeated surgical intervention (bleeding occurred in the area of the removed gallbladder bed). No postoperative bleeding, except, was registered;
the following data was obtained as a result of the the most large-scale of the
published studies, conducted on the basis of 4 medical centers in various regions of the
Russian Federation (8), including 89 patients of general surgical profile, who underwent
both open and laparoscopic surgeries on the abdominal cavity:
The Hospital Surgery Clinic of the Regional Budgetary Institution of Health "City
Clinical Hospital No. 4" of the city of Ivanovo" (39 patients) achieved stable hemostasis
during open surgeries. At that, the agent (25-50 ml, exposure time - 2-3 minutes) was
applied on an average drape, which was applied to a wound treated with a dry drape;
The Surgery Center of the NGHCI CCH No. 1 of the Russian Railways JSC
(Moscow) 27 patients, both males and females, aged 30 to 76, 16 of whom were diagnosed with oncological pathology, 11 of whom had acute surgical pathology in the abdominal cavity, major vessels and skeletal bones) registered the effectiveness of the agent in 85.2% of cases (23 patients). In 2 cases (7.4%), relapsed bleeding occurred, and for 2 other patients (7.4%) the agent displayed no effect: in one patient with septic shock on the background of chronic cholangitis with low and unstable pressure, the continuous bleeding from the adhesions of the abdominal cavity was registered, which was stopped with tamponade and fibrinogen and thrombin plates; in case of the second patient, bleeding from the ureter continued because of its connection to aortic aneurysm, which required repeated intervention. in the Endoscopy Department of the SBHI RCH No. 3, of the city of Chelyabinsk, the agent was successfully used during endoscopic interventions on 11 male patients aged 46 to 77; in the Endoscopy Department of the Central District Hospital of the city of Kineshma, Ivanovo region, 12 patients showed the effectiveness of the PPA SS in comparison with epsilon-aminocaproic acid.
During operations for hernia of the anterior abdominal wall, Chikaev et al.
during a postoperative period in patients when the intraoperatively studied agent was used as a local hemostatic after the main stage of the operation before suturing of a surgical wound, there was registered a less drainage than in patients who did not receive it: respectively 10 ml/day and 30-40 ml/day, which led to a later removal of drains in the
"reference" group. In surgical vertebrology, the situation is somewhat different from the "general traumatology". To date, there are two main types of approaches to spinal column: anterior approaches are used by a very limited number of vertebrologists, moreover, due to the anatomical features, their use are not effective and safe at all levels;
posterior approaches are technically simpler for the majority of specialists and are
applicable at all levels, encompassing anatomical structures from the occipital bone and
craniovertebral transition to the sacrum, but they are accompanied by a greater blood loss during execution, bigger number of complications, which is associated with the need to separate significant muscle volumes from the osseous structures (13). When they are
exposed to the instrumentation (wound retractors, hooks, mirrors, electrocoagulator), there inevitably occurs local bleeding from small-caliber vessels, which is usually small in volume, but certainly requiring a stop. A relatively rare intraoperative complication is
damage of the segmental arteries, location of which in hard-to-reach areas of the surgical
wound and complexity of ligation limits the choice of hemostatic agents: as a rule, the use
of a coagulator, temporary clamping of muscle tissues (together with underlying vessel)
using tweezers or a clamp, tamponade of the wound with gauze material and the use of
means that are not specific hemostatics (3% hydrogen peroxide solution) remain at the
disposal of the operating surgeon. According to our experience, a hemostatic sponge
cannot always be effectively applied, since its unreliable fixation at the bleeding point can
minimize the effect. The bone wax remains a 'narrowly specific' hemostatic agent, which is used only against one type of bleeding - from the cells of the cancellous bone. Despite the recent rapid development and use of a variety of systems for minimally
invasive dorsal surgery, it is economically impossible to quickly equip all existing clinics
and departments with them; while the acquaintance of surgeons with new methods of
surgical interventions, especially in vertebrology, also involves certain expenses, including
administrative ones. Thus, vertebrology remains the area of traumatology and
orthopedics, where the issue of using simple and effective hemostatic agents is very
relevant, and which are subject to the following requirements:
local action (e.g., when applying a drape with a hemostat to a bleeding vessel in
surgical wound); no generalized effect on the hemostasis system;
pronounced hemostatic effect with the absence of undesirable side effects (absence
of allergic reactions and toxicity). Pronounced effect in conditions of hemodilution, as well as a decrease in the concentration of coagulation factors (as well as plasma proteins in the blood) is an additional requirement for the hemostatic agent. The said situation can occur in case of a significant blood loss and/or long time of vertebral surgeries, when it is necessary to replenish the VBC not only with erythrocyte and plasma components, but also with the infusion solutions (both crystalloids and colloids).
The agent in question meets the above requirements. The data we obtained confirm
the reliability of its effect on the reduction of the volume of perioperative (intra- and
postoperative) blood loss occurring in case of diffuse and muscular bleeding. Despite the
lack of data on its application in case of other spinal pathologies, our data allow us to
speak with certain amount of confidence about the advisability of using the partial
polyacrylic acid silver salt agent for hemostasis in the surgery for degenerative and dystrophic changes and spinal injuries. Acting purely as a local hemostatic, the agent
turned to be effective in reducing diffuse muscle bleeding from the surgical wound walls.
To stop bleeding from other anatomical structures, other proven methods such as bone wax and bipolar electrocoagulation should be applied.

Conclusions

Vertebrology is an area of orthopedics, where there is a practical need for new hemostatic agents. Partial silver salt of polyacrylic acid can be considered as such and can be successfully applied in the practice of surgical vertebrology: Its use in case of decompressive interventions in the lumbar spine with fixation of 1-3 segments, allowed to effectively reduce the volume of blood loss, both during intra- and post-surgery period.
Even considering the use in the reference group of various and combined hemostasis
methods, the volume of blood loss in the main group was significantly lower (p <0.05).

Results integrity limitation

The study presents the results without analyzing the impact on the blood loss level of such factors as the treatment invasiveness, blood pressure level during the surgery, duration of fixation (of 1 to 3 segments), anticoagulants administration and some others. However, given the relatively narrow criteria for inclusion/exclusion and patient randomization in the course of selection to the reference group, with certain amount of confidence, we can talk about the uniform characteristics of patients.

Competing interests

The authors received no remuneration for execution of this study There are no competing
interest whatsoever, that need to be notified of.