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 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 3  |  Issue : 1  |  Page : 14-19

Comparison between effects of two anesthetic techniques on acute stress proteins and d-dimer in patients undergoing lower limb orthopedic surgery


1 Professor of Anaesthesia and Surgical Intensive Care, University of Alexandria, Alexandria, Egypt
2 Professor of Anaesthesia and Surgical Intensive Care, University of Alexandria, Alexandria, Egypy, Egypt
3 Assistant Professor of Anaesthesia and Surgical Intensive Care, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
4 Assistant Professor of Clinical and Chemical Pathology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
5 Anaesthesiologist at Departement of Anaesthesia, Alexandria University Hospitals, Alexandria, Egypt

Date of Submission14-Sep-2015
Date of Acceptance22-Nov-2015
Date of Web Publication15-Jun-2016

Correspondence Address:
Atef G Omar
Anaesthesiologist at Departement of Anaesthesia, Alexandria University Hospitals, Alexandria
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2356-9115.184079

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  Abstract 

Background Anesthetic techniques may modulate the extent of endocrine–metabolic response to surgery. Attenuation of the endocrine–metabolic response may reduce the frequency of postoperative complications. The aim of this study was to compare the effect of two different anesthetic techniques (combined general anesthesia with epidural blockade vs. combined spinal–epidural blockade) on acute stress proteins including serum albumin, C-reactive protein, leptin, cortisol, and d-dimer in patients undergoing lower limb orthopedic surgery.
Materials and methods After approval of the ethics committee of Alexandria Faculty of Medicine and having an informed consent from every patient, the present study was carried out on 40 patients ASA I or II physical status. Group I; 20 patients received combined general anesthesia with epidural blockade and group II; 20 patients received combined spinal–epidural blockade. Epidural analgesia was activated just before wound closure.
Results The blood loss was statistically significantly low in group II. The mean values of serum albumin were significantly lower in the group II at 3 and 24 h postoperatively. There were no significant differences between preoperative and 24 h postoperative serum cortisol. Serum cortisol levels were significantly lower in the group II at 3 h postoperatively. There were no significant differences in serum leptin concentrations and preoperative plasma d-dimer. Plasma d-dimer concentrations were significantly higher in the group I at 3 h postoperatively and at 24 h postoperatively.
Conclusion Subarachnoid block decreases postoperative pain score and reduces blood loss in comparison with general anesthesia. It reduces the acute stress response and acute stress proteins (albumin, cortisol). It did not reduce C-reactive protein. It reduces plasma d-dimer level after lower-limb orthopedic surgery in comparison with general anesthesia.

Keywords: anesthetic techniques, orthopedic surgery, stress proteins


How to cite this article:
Areda EA, Shafshak WM, Zanaty OM, Hadidi AS, Omar AG. Comparison between effects of two anesthetic techniques on acute stress proteins and d-dimer in patients undergoing lower limb orthopedic surgery. Res Opin Anesth Intensive Care 2016;3:14-9

How to cite this URL:
Areda EA, Shafshak WM, Zanaty OM, Hadidi AS, Omar AG. Comparison between effects of two anesthetic techniques on acute stress proteins and d-dimer in patients undergoing lower limb orthopedic surgery. Res Opin Anesth Intensive Care [serial online] 2016 [cited 2017 Dec 14];3:14-9. Available from: http://www.roaic.eg.net/text.asp?2016/3/1/14/184079


  Introduction Top


Acute phase response is a complex series of reactions initiated as a response to infection, surgery, trauma, or malignancy. These reactions have a goal to prevent tissue damage, isolate and destroy infectious organisms, and to activate reparation processes which have a task to restore normal body functions [1],[2]. Acute phase response is also defined as a state in which the concentrations of acute phase proteins (APPs) increase [positive APPs: fibrinogen, C-reactive protein (CRP)] or decrease (negative APPs; albumin, transferrin, insulin growth factor I). Stress response to surgery is characterized by neurohumoral, immunologic, and metabolic alterations [3],[4]. Surgery-related metabolic and endocrine derangements lead to adverse effects, including increased oxygen consumption, catabolism, and impaired immune function. These derangements have been associated with poor postoperative course and clinical outcome [5],[6]. Leptin is a cytokine-like molecule and is secreted in proportion to the adipose tissue mass. It has been suggested that leptin may be involved in the acute stress response after surgery [7],[8],[9],[10]. Temporal relationship was shown between circadian variation of serum levels of leptin and cortisol, with cortisol peak following leptin peak [11]. Cortisol has an inhibitory role on APP response in a chronic setting and stimulatory effect in an acute setting. After an acute injury, there is first a physiological increase in cortisol, followed by leptin and APPs increase [12],[13]. CRP is one of the main APPs. A significant correlation between leptin and CRP levels indicates that leptin costimulates APPs synthesis during the acute phase response following an inflammatory stimulus [9]. d-dimer is a fibrin degradation product, a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis. While a negative result practically rules out thrombosis, a positive result can indicate thrombosis, but does not rule out other potential causes such as trauma, recent surgery, liver disease, high rheumatoid factor, inflammation, pregnancy, and malignancy [14]. Research has been conducted to find a 'stress-free anesthetic technique' to limit neuroendocrine, inflammatory, and immune responses [4] as attenuation of the endocrine–metabolic response may reduce the frequency of postoperative complications [15],[16].


  Materials and Methods Top


The present study was carried out on 40 patients ASA I or II physical status aged 20–60 years at El-Hadara University Hospital scheduled for lower limb orthopedic surgery. Exclusion criteria were patients with congestive heart failure, endocrinal and metabolic disease, malignancy, signs of infection or inflammation, pregnancy, malnutrition, contraindication to neuroaxial blockade, psychiatric disorders and drugs or alcohol abuse; patients who rejected the anesthetic technique scheduled according to randomization were excluded. After approval of the ethics committee of Alexandria Faculty of Medicine and having an informed consent from every patient, patients were randomly categorized into two groups by closed envelop method (20 each): group I; 20 patients received combined general anesthesia with epidural blockade, and group II; 20 patients received combined spinal–epidural blockade preoperatively, after detailed medical and surgical history, complete clinical examination, and routine laboratory investigations; all patients were fasted 6 h for solid food and received midazolam 0.1 mg/kg body weight intravenously 1 h before surgery. Preloading was done with Ringer acetate 10 ml/kg body weight over a period of 15–20 min. According to the studied groups, group I patients received combined general–epidural anesthesia. With patients in the sitting position after aseptic wash and sterile draping, an 18-G Tuohy epidural needle was introduced into the epidural space through L2–L3 or L3–L4 intervertebral space applying loss of resistance technique. Keeping the needle in the epidural space, an epidural catheter was inserted carefully. The epidural catheter was fixed after keeping 3–5 cm in the epidural space with the tip-directed cephalad. Then the patient turned supine. A test dose of 3 ml (2% lignocaine with 1: 200 000 adrenalines) was given. General anesthesia induced then at the end of surgery, residual muscle relaxation antagonized using neostigmine (0.04 mg/kg) with atropine (0.02 mg/kg). Postoperative epidural analgesia was started just before wound closure using 10 ml of 0.125% bupivacaine then intermittent top-up doses of 8 ml every 6 h for 24 h. Group II patients received combined spinal–epidural anesthesia. With patients in the sitting position after aseptic wash and sterile draping, the epidural catheter was fixed through L2–L3 or L3–L4 intervertebral space. Subarachnoid blockade was performed with 2.5 ml of hyperbaric bupivacaine (0.5%)+25 μg fentanyl injected through spinal needle at L4–L5 intervertebral space under complete aseptic technique and the patient turned supine. Postoperative epidural analgesia started just before wound closure using 10 ml of 0.125% bupivacaine then intermittent top-up doses of 8 ml of 0.125% bupivacaine every 6 h for 24 h. Intraoperative monitoring of heart rate, noninvasive arterial blood pressure, oxygen saturation, and ECG using multichannel monitor (Viridian 24; Hewlett Packard, Germany) and the following parameters were measured: oxygen saturation (SpO2%), heart rate (beats/min), noninvasive measurement of mean arterial blood pressure (mmHg). Hypotension is defined as a 20% decrease, from baseline mean blood pressure. They were continuously monitored and recorded every 5 min for the first 15 min then every 20 min till the end of surgery. Amount of blood loss and amount of blood transfused were measured. Severity of postoperative pain was assessed by a visual analogue scale (VAS). If analgesia was not satisfactory (VAS >3 cm), supplementary analgesia was provided by meperidine 0.5 mg/kg intravenously. The total amounts of supplemental analgesics administered were recorded. Three consecutive venous blood samples were collected in two tubes; the first one plain tube for serum and the second citrated tube for d-dimer, preoperatively, before induction of anesthesia (baseline, sample 1), postoperatively at 3 h (sample 2), and postoperatively at 24 h (sample 3). The investigators who performed the sampling and analysis were blinded to the group. After being centrifuged, serum was stored at −20°C until analyzed for; serum albumin measured on the dimension (Siemens), CRP measured using nephelometer (Siemens) by Cardiophase hsCRP, cortisol measured by competitive immunoassay by chemiluminescent technology using the ADVIA Centaur, and Plasma for d-dimer measured using BF II coagulometer (Siemens). Serum leptin was measured by enzyme-linked immunosorbent assay technique. Data were fed to the computer and analyzed using IBM SPSS software package version 20.0. Qualitative data were described using number and percent. Quantitative data were described using range (minimum and maximum), mean, SD, and median.


  Results Top


There were no significant statistical differences between the two studied groups as regards age, weight, height, and duration of surgery. There were no significant differences between the two studied groups as regards heart rate and oxygen saturation at all measured times. There were no significant differences in the mean blood pressure preoperatively and intraoperatively (before 5 and after 35 min), while the mean blood pressure was significantly lower in group II compared with group I intraoperatively (after 5 and up to 35 min) ([Figure 1]).
Figure 1: Comparison between the two studied groups regarding changes in the mean blood pressure (mmHg).

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The blood loss was statistically significantly low in group II compared with the group I (P < 0.001). No patients in the two studied groups required blood transfusion. There was no significant difference in mean VAS pain scores at 3 h between both the groups. Three patients in the group I required intravenous meperidine analgesic supplementation. No significant difference was found between both the groups regarding overall rate of postoperative complications. There were no significant differences between preoperative serum albumin (P = 0.625). But serum albumin concentrations decreased postoperatively in both the groups. The mean values of serum albumin were statistically significantly lower in the group II compared with the group I at 3 h (P = 0.015) and 24 h postoperatively (P = 0.044) ([Figure 2]).
Figure 2: Comparison between the two studied groups regarding serum albumin.

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The two studied groups showed no significant differences between serums CRP. CRP concentrations increased postoperatively in both groups, but with no significant differences. No significant differences between preoperative and 24 h postoperatively serum cortisol. But serum cortisol concentrations increased postoperatively in both the groups. Serum cortisol levels were significantly lower in the group II at 3 h postoperatively ([Figure 3]).
Figure 3: Comparison between the two studied groups regarding serum cortisol.

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No significant differences were found between preoperative serum leptin (P = 0.892). Serum leptin concentrations increased postoperatively in both the groups, but with no significant differences ([Figure 4]).
Figure 4: Comparison between the two studied groups regarding serum leptin.

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Plasma d-dimer concentrations increased postoperatively in both the groups. No significant differences between preoperative plasma d-dimer. Plasma d-dimer concentrations were statistically significantly higher in the group I compared with the group II at 3 h postoperatively (P = 0.003) and at 24 h postoperatively ([Figure 5]).
Figure 5: Comparison between the two studied groups regarding plasma d-dimer.

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  Discussion Top


Various studies reported that even under anesthesia of sufficient depth, surgical stimulation leads to hormonal and metabolic changes [17],[18]. In the present study, as regards to the changes in the heart rate, there were no statistically significant differences between the two groups regarding heart rate values. Carpenter et al. [19] explained that the cardiac accelerator fibers are sympathetic efferents (Tl–T4), which increase heart rate when stimulated and decrease it when blocked due to the unopposed vagal activity. In the present study, the sympathetic blockade was below T4. As regards changes in the mean arterial blood pressure, preoperatively there were no statistically significant differences between the two groups. After 5 min of the intrathecal injection, the mean arterial pressure was significantly lower in group II and this significant reduction lasted up to 35 min intraoperatively in group II. This may be explained by the effect of subarachnoid blockade on the cardiovascular system [19].

Regarding blood loss, in the present study the blood loss was significantly low in group II compared with group I (P < 0.001). A meta-analysis by Guay included 24 studies on surgical blood loss and blood transfusion requirements after different types of total hip replacement, spinal fusion surgery, and others. Guay concluded that neuroaxial anesthesia confers a highly significant reduction in blood loss and transfusion [20]. In agreement with the present study, the study of Heidari et al. [21] showed that the mean of blood loss during hip surgery was significantly more in patients who received general anesthesia than in those who received neuroaxial anesthesia. Mauermann et al. [22]; in a prospective controlled meta-analysis reported that patients undergoing total hip replacement under spinal anesthesia had less blood loss than patients receiving general anesthesia. Neuroaxial anesthesia blocks a and b-adrenergic receptors, leads to reduction of vascular tone, and blood pressure [23],[24].

With regards to serum albumin, the mean values of serum albumin were statistically significantly lower in groupII compared with group I at 3 h (P = 0.015) and 24 h postoperatively (P = 0.044). Buyukkocak and colleagues investigated the acute phase response to circumcision and the effects of anesthesia on this response. They found that albumin values 24 h before surgery and on admission were similar for all groups. The values remained steady throughout the study and did not change significantly [1]. Decreased serum albumin in the present study may be partly explained by alterations in vascular permeability and by dilution effect secondary to intravenous fluid infusion. Vascular permeability and inflammatory phenomena that follow surgery and trauma lead to tissue edema with protein leakage to the interstitial space. In acute phase response, there is a decrease in gene transcription rate of albumin m RNA and albumin synthesis [25],[26].

With regard to serum CRP, concentration increased postoperatively in both the groups, but with no statistically significant differences between both the groups. In agreement with the present study, Buyukkocak et al. [27] reported that the anesthesia techniques did not influence acute phase response based on CRP levels at admission, at delivery, and 24 h after cesarean delivery. In agreement with the present study, increase in CRP was observed after 24 h in patients undergoing abdominal hysterectomy, and in patients undergoing cholecystectomy also [28],[29]. Schwab et al. [30] reported that CRP levels increased on the first and third postoperative days with no difference between endoscopic and conventional hernia repair; they obtained the lowest inflammatory response and CRP increase in local anesthesia subgroup. In the present study, CRP results are consistent with the previous studies where CRP significantly increased after surgery in both groups regardless of the anesthetic modality [6].

As regards to serum cortisol, the present study showed no statistically significant differences in preoperative serum cortisol and 24 h postoperatively between both the groups. However, serum cortisol concentrations increased postoperatively in both the groups. Serum cortisol levels were statistically significantly lower in the group II at 3 h postoperatively (P < 0.001). In agreement with the present study, Buyukkocak et al. [2] found lower perioperative cortisol levels in patients receiving regional anesthesia (the saddle block group) than in those under general anesthesia. Hogevold et al. [31] evaluated patients undergoing total hip replacement surgery under general or regional (combine spinal/epidural) anesthesia; significantly lower cortisol levels were found during the operation in the regional anesthesia group. In a study by Cigdem et al. [32] one group received general anesthesia and the other group received spinal anesthesia; a smaller rise in the cortisol level was observed in the spinal anesthesia group. In the present study, these effects may be attributed to blocking afferent and efferent pathways in the sympathetic and the somatic nervous system that may suppress the neuroendocrine activation by surgery during spinal anesthesia in the group II.

As regards to serum leptin, the two studied groups showed no statistically significant differences between preoperative serum leptin (P = 0.892). Serum leptin concentrations increased postoperatively in both groups, but with no statistically significant differences. In agreement with the present study, Buyukkocak and colleagues found that leptin concentrations increased postoperatively with no significant difference between general and regional anesthesia. The increase in leptin was explained by the increase in hormones related to surgical stress (cortisol) [2]. Kain et al. [10] measured plasma leptin and cortisol in women before, during, and after total abdominal hysterectomy, the anesthetic technique was strictly controlled, balanced anesthesia; they found that leptin decreased 2 h and was elevated 24 h after surgery; they explained that one of the reasons of the initial decrease was perioperative fasting. Cho et al. [33] reported a sudden decrease in leptin levels immediately after gastrectomy and an increase 24 h after surgery; that was explained by the catecholamine release triggered by surgery.

As regards to plasma d-dimer, its concentrations increased postoperatively in both the groups. Plasma d-dimer concentrations were statistically significantly higher in the group I compared with the group II at 3 h postoperatively (P = 0.003) and at 24 h postoperatively (P < 0.001). On the contrary, Brueckner et al. [34] found that there were no significant differences in the timely course of the hemostatic markers including d-dimer at any given time point between general and regional anesthesia groups in patients undergoing total hip arthroplasty. In agreement with the present study, Khafagy et al. [35] found that general anesthesia showed a marked significant increase in specific hemostatic and fibrinolytic parameters including d-dimer compared with epidural anesthesia. Wang et al. [36] studied the influences of different anesthesia techniques on stress response, coagulation, and fibrinolytic function in patients undergoing hysterectomy; they reported that epidural anesthesia can preserve fibrinolytic function after lower-abdomen surgery by the inhibitory effects on surgical stress, PAI-1 and other mechanisms.


  Conclusion Top


Subarachnoid block decreases postoperative pain score and reduces blood loss in comparison with general anesthesia. It reduces the acute stress response and acute stress proteins (albumin, cortisol). It did not reduce CRP. There was a negative correlation between serum leptin and excessive intraoperative blood loss. Subarachnoid block reduces plasma d-dimer level after lower-limb orthopedic surgery in comparison with general anesthesia by the inhibitory effects on surgical stress.


  Acknowledgements Top


Conflicts of interest

There are no conflicts of interest.

 
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