**5.1 Material and methods**

Patients:

22 Recent Advances in Arthroplasty

system which depends on both the nerve blockade and the administrated local anesthetic

The results of study revealed the influence of the bupivacaine presence for the reduction of the synthesis of immunoglobin IgG, IgM, IgA and enhancing the granulocytes phagocytosis. The epidural anesthesia with bupivacaine was associated with lower serum concentration of gammaglobulins (IgG, IgM, IgA) and the complement components C3

Bupivacaine is the most popular, long acting local anesthetic with a wide range of administration for peripheral and central nerves blockades. Ropivacaine is also a long acting local anesthetic drug similar to bupivacaine in terms of pharmacological activity, but in contrast to is characterized by the lower cardiotoxity. Lidocaine is the most often and widely used local anesthetic for the peripheral nerves blockades especially in the combination with the bupivacaine for more beneficial balance of duration and onset. Lidocaine is also classified as an anti-arrhythmic agent. Bupivacaine in comparison with the lidocaine shows more potent effect on the function of leukocytes. However, the ropivacaine has been shown its anti-inflammatory properties related to the inhibition of leukocyte function such as the rolling/ adhesion which accompanies the early stage of the local inflammatory response. Moreover, both the ropivacaine and lidocaine could inhibit the CD11b/CD18 up-regulation and the L-selectin down-regulation on neutrophils migration between endothelial cells. There has been found that the effect of the lidocaine was 2.5 times

The extent of nerves blockade, occurs due to regional anesthesia, appears to have an influence on the neuro-endo-immune response intensity. The endocrine - metabolic stimulation following the surgical procedure can be inhibited by the afferent nerves blockade. The blockade of motor, sensory and afferent sympathetic fibers leads to resulted in predominance of parasympathetic system resulting changes in circulation The intensified circulation may reduce the release of cytokines associated with the tissue ischemia and hypoxia but from the other site a marked low perfusion triggers cytokines burs following hypoxia. The degree of blood flow distribution is directly related to the level of the blockade. It was shown that usage of continuous epidural anesthesia reduced the hormonal stress response and improved the protein metabolism, but it didn't play any significant role in the stimulation of inflammatory response *(*Kehler, 2000*).* Although in comparison with general anesthesia, the epidural anesthesia demonstrate less effect on the activity of natural

The spinal anesthesia is considered as the standard procedure for the orthopedic surgery. The choice of the central blockade is influenced with many benefits such as reduced risk of the postoperative cardiovascular, pulmonary and thromboembolic complications. The prolonged analgesia which spreads onto post operative period is also worth to be emphasized. The patients who underwent surgery with the spinal anesthesia would require greatly less opioids which action is not neutral to the immune system. Further advantages of the regional anesthesia, especially in the RA patients, has ability to avoid the difficult and traumatic intubation. The majority of patients with advanced RA demonstrated the atlanto-axial instability with the great risk of spinal cord compression

Many studies have revealed that the regional anesthesia can attenuate the perioperative immunosuppression related to the stress surgery. There are evidences demonstrating a greater number of the Th1 compare to Th2 (CD4+ T and CD8+ T cells) and increased the

lower than the ropivacaine (Martinsson et al., 1997; Zhang et al., 2000).

killer cell (NK), T and B cells (Tonnesen et al., 1988).

(Lisowska et al., Jan 2007; 2008).

drugs (Lisowska, 2008).

and C4 (Gajdosz, 1994).

The 37 patients with long term rheumatoid arthritis scheduled for knee arthroplasty under spinal anesthesia. Hyperbaric bupivacaine in dose 4 mg was used in all cases.

The Stress Response and Its Functional Implications in the Immune

evaluated DAS-28. Group 1 (G1) DAS-28 <5, group 2 (G2) DAS-28≥5

Age (yr) 56. 56.8±11.2 61.4±5.9 0.02 RA duration (yr) 18.5±7.3 20.2±8.2 0.61 DAS-28 4.09±0.59 5.9±0.75 0.39

Number of patients 17 20

crystaloids: 3300± 376

groups in terms of volume given fluids and tourniquet duration.

baseline value indicated small increase of IL-6 in patients in this group.

difference is particularly shown in the clinical observation.

SaO2: G1 97.2±1.3 G2 96.5±1.3, the values are mean ±SD.

and groups for IL-6 (Fv1=4, v2=171 =0.15, p=0.9650).

of IL-6 was kept on the similar levels after operation.

with preoperative values (Fig.2).

**5.2 Results** 

physical status II.

Intravenous fluids

Tourniquet duration

Data are mean ±SD or n

(ml)

(min)

Response After Surgery in Patients with Chronic Inflammation Undergoing Arthroplasty 25

The study population consisted of 37 patients (35 women, 2 men) with a primary diagnosis of rheumatoid arthritis underwent total knee arthoplasty under spinal anesthesia. ASA

Patients were divided into two groups depending on the activity of the disease being

Group 1 Group 2 P value

crystaloids: 3300±316.0

coloids: G1 500 coloids: 530±129 1.0

86.6±14.6 95.3±13.5 0.77

Table 1. Characteristics and surgical data of patients divided into DAS-28 groups (G1, G2) Details of 37 patients studied are shown in Table 1. The significant difference was observed in relation to age between groups. By contrast, there were no significant differences between

With regard to the DAS, the difference between groups is not statistically significant but this

No significant differences were observed with cardiovasculary parameters between groups during observation: MAP (p=0.61) and SaO2 (p=0.98). MAP: G1: 89.6±11, G2: 86.7±10.2 and

Analysis of concentration level of IL-6 shown statistically significant difference between groups (Fv1=1, v2=171 =41.23, p<0.0001). The was no found significant differences in concentration level of IL-6 in time segments (Fv1=4, v2=171 =0.13, p=0.9721). No interaction time

The concentration of IL-6 before operation was particularly higher in patients in G2. Moreover, a comparison of value of IL-6 concentration thirty-six hours after surgery with

Taking into consideration the range of IL-6 value it can be concluded that the concentration

There were none changes in concentration of IL-6 during observation in patients in G1 (Fig. 1). In terms of TGF-β concentration, the analysis of results shown no statistically significant variation of mean value across time (Fv1=4, v2=168 =0.29, p=0.8867). There was no found the significant difference between groups (Fv1=2, v2=168 =2.79, p=0.0966). However, in opposition to IL-6, in both group the values of TGF-β measured at 36 hour were lower in comparison

0.5

Standard monitoring including continuous electrocardiogram, nonivasive automated blood pressure and pulse oxymetry. Cardiovascular and respiratory monitoring was continued at the time following surgery. All patients were transferred in the postoperative care unit after the operation.

Crystalloids, colloids were used perioperatively. Homologous blood was used for transfusion depending on the patient's requirements.

Patients with long-term steroids therapy received additional steroid doses during postoperative period in a predefined regiment.

Thromboprophylaxis with low-molecular weight heparin was given.

All patients received antibiotic prophylaxis with Cephazolin 1g on induction and 1 g eighthourly within 3-5 days.

For postoperative pain relief, they were given standard analgesic drug consisting of opioid and paracetamol.

The tourniquet was used in all patients. Tourniquet pressure was 350 mmHg.

Exclusion criteria included an ASA≥3, BMI>30 (obesities), Hb≤9g/dl, treatment with biologic agents, allergy to local anesthetics, contraindications to spinal anesthesia.

The duration of RA was evaluated and the Disease Activity Score-28 (DAS28) was calculate for all patients before operation. The set of questionnaires was used, the Disease Activity Score-28 was assessed by the number of swollen and tender joints, erythrocyte sedimentation rate (ESR, mm/h) and general health assessment on a visual analog scale (VAS).

During observation the normally physical examination of respiratory system was performed in all patients. No patient had significant tachycardia, tachypnea or other symptoms of atelectasis. Moreover, none of patient complained of sharp pain burning sensation in urine tract that might be a sign of infection and no patient had documented wound complication during observations.

Patients were divided into two groups depending on the activity of the disease being evaluated DAS28. The patients with DAS-28 score lower than 5.0 were classified into the group 1 (G1) and the patient with DAS28 score≥5 were classified into the group 2 (G2).

Blood samples:

Samples of venous blood were taken before induction of anesthesia (a baseline sample-0 h) and at 6, 12, 24, 36 hours (6h, 12h, 24h, 36h) after the end of surgery. Blood was collected in 5 ml pyrogen –free tube, the samples were centrifuged at 3000 rpm for 10 min then serum was separated and stored at -70oC for future analysis.

The serum concentration of interleukins IL-6, TGF-β and C-reactive protein (CRP) were determined in all patients. Serum CRP was determined rapidly after obtaining.

The serum concentration of IL-6 was determined with a commercially available using ELISA kits (R&D System).

TGF-β was determined with using DuoSet ELISA kits (R&D System). All determinations were performed according to the manufacturer's instructions.

CRP was determined using routine diagnostic test (dry chemistry) in analizator Vitros 250.

Statistical analysis of results was performed using a standard computer application Statistica version 9. Continuous parametric data were assessed using one-way analysis of variance (ANOVA). Statistical significance was considered at the p ≤0,05

The study was approved by the medical Ethics Committee of the Institute of Rheumatology and informed written consent was obtained from each patient all the patients.
