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Bilateral paravertebral block in advanced schistosomal liver disease: A prospective study Abou Zeid HA, Al-Ghamdi AA, Abdel-Hadi MS, Zakaria HM, Al-Quorain AA, Shawkey MN - Saudi J Gastroenterol
Saudi Journal of Gastroenterology
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ARTICLES Table of Contents   
Year : 2004  |  Volume : 10  |  Issue : 2  |  Page : 67-77
Bilateral paravertebral block in advanced schistosomal liver disease: A prospective study


1 Department of Anesthesia, King Fahad Hospital of the University, Al Khobar, Saudi Arabia
2 Department of Surgery, King Fahad Hospital of the University, Al Khobar, Saudi Arabia
3 Department of Medicine, King Fahad Hospital of the University, Al Khobar, Saudi Arabia

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Date of Submission 09-Jul-2003
Date of Acceptance 06-Jan-2004
 

   Abstract  

Background: Surgery in patients with schistosomal liver disease is usually associated with high risks of morbidity and mortality. Bilateral paravertebral block (BPVB) has been advocated as a useful technique for ventral abdominal hernias' repairs. Aim of the study: To compare the efficacy of BPVB with general anesthesia (GA) for anterior abdominal wall hernias in advanced schistosomal liver disease patients. Patients and Methods: Sixty patients were randomly allocated into two groups to receive either GA or BPVB. Variables were hospital stay, hemodynamic stability, postoperative nausea and vomiting (PONY), postoperative pain measured on a visual analogue scale (VAS) with assessment of the hepatic cell integrity using glutathione S transferase alpha (GSTA) and other liver enzymes. Results: The main significant finding was an apparently significant shorter length of hospital stay following BPVB as compared with GA in patients (P < 0.005). Conclusions: BPVB was superior to GA following abdominal ventral hernia repair in schistosomal liver fibrosis patients

Keywords: Schistosomiasis, hepatic fibrosis, Bilateral Paravertebral Block.

How to cite this article:
Abou Zeid HA, Al-Ghamdi AA, Abdel-Hadi MS, Zakaria HM, Al-Quorain AA, Shawkey MN. Bilateral paravertebral block in advanced schistosomal liver disease: A prospective study. Saudi J Gastroenterol 2004;10:67-77

How to cite this URL:
Abou Zeid HA, Al-Ghamdi AA, Abdel-Hadi MS, Zakaria HM, Al-Quorain AA, Shawkey MN. Bilateral paravertebral block in advanced schistosomal liver disease: A prospective study. Saudi J Gastroenterol [serial online] 2004 [cited 2014 Mar 5];10:67-77. Available from: http://www.saudijgastro.com/text.asp?2004/10/2/67/33339


Schistosomiasis is a wide spread endemic disease affecting different parts of the world; it is prevalent in some Middle Eastern countries such as Egypt, Sudan and Saudi Arabia [1],[2] . Schistosomal liver disease affects around 20 millions persons in Egypt alone [3] .The disease affects the physical status and the liver, ending with liver insufficiency and failure. Coinfection with viral hepatitis (B or C) is considered as an additional risk factor [4],[5] . General and/or regional anesthesia may affect the liver cell integrity [6] . The measurement of transaminases activity in plasma is the most widely used method of assessing hepatocellular integrity. Meanwhile, serum levels of GSTA have been introduced as a specific accurate and sensitive indicator for hepatocellular damage and could express very minute trauma to liver cells [7] Paravertebral block was first described in 1905 by Sellheim of Leipzig as a replacement for spinal anaesthesial and is used for surgical procedures. The paravertebral space is a triangular area, which contains the intercostal nerve (and its dorsal ramus), the rami communicantes and the sympathetic chain. Posteriorly is the costotransverse ligament, anteriorly the parietal pleura, medially the postero-lateral aspect of the vertebra and laterally the posterior intercostal membrane. Local anaesthetic injection into this space produces both a somatic and sympathetic block over several dermatomes [8] Paravertebral blockade (PVB) has been advocated as a useful technique for different types of surgery. The success of unilateral somatic paravertebral nerve block (PVB) has been reported in both adults and children [8],[9] . This anesthetic method produces high quality intra and postoperative analgesia and has been shown to modify the stress response to surgical stimulation e.g thoracotomy, breast surgery and inguinal hernia repair [10],[11],[12],[13],[14],[15] A substantial reduction of postoperative nausea and vomiting together with long­lasting postoperative analgesia has recently been described after the use of PVB in patients undergoing breast surgery and orthopedic surgery [16],[17],[18],[19] Bilateral paravertebral block for analgesia was also used successfully in abdominal vascular surgery [20] .

Currently, only limited case series have been published about the bilateral use of PVB for surgical anesthesia [21],[22] . The aim of the present randomized-blinded study is to study the efficacy of bilateral PVB (BPVB) with catheter insertion compared to GA as a technique for anterior abdominal wall hernia repair in chronic schistosomal liver disease, and to follow up the liver cell integrity function before and after both techniques. This research proposal was approved by the local medical ethics committee and it has been carried out according to Helsinki-declaration.


   Patients and methods   Top


Sixty patients with schistosomal hepatic fibrosis classified as ASA physical status II and III undergoing elective anterior abdominal wall hernias repair were included in the study. Patients with respiratory, cardiac, renal insufficiency (creatinine >133umol/L), primary or secondary hepatoms, fibrile and allergic patients were excluded from this study. The study excluded patients who had prothrombin time equal or more than double normal values. The schistosomal hepatic fibrosis patients were chosen according to the laboratory investigations, schistosomal antibodies and liver biopsy whenever it was feasible. The patients were randomly allocated using dark opaque envelopes into two groups (30 patients each): group I received GA and group II received bilateral paravertebral block with catheter insertion. No premedication was given to patients at night of surgery. In the operating room, patients were given midazolam 0.05mg kg -1 intravenously (IV). General anaesthesia was induced to group I (30 patients), with IV fentanyl (1.5(µg. kg -1 ) and propofol (2-2.5mg. kg -1 ) followed by cistracrium (1.5mg kg-1) to facilitate intubation and relaxation during surgery. tracheal intubation was done with a suitable cuffed tube under direct vision laryngoscopy. Anesthesia was subsequently maintained with propofol infusion (total intravenous anesthesia), nitrous oxide 50% and oxygen 50%. The propofol infusion rate was adjusted between 6-10 mg/Kg/h with the intention of keeping heart rate and blood pressure within + 20% of pre­induction levels to guarantee the stability of liver perfusion. Mechanical ventilation was used, with standard monitoring using Datex-OhmedaS/5 machine (Helsinki,Finland) to keep EtCO2 between 32-40mmHg. At the end of surgery, extubation was done without reversal drugs as we used cisatracurium, which had self degradation by Hoffmann elimination and ester hydrolysis. Patients in group 11 (30 patients) were allocated to receive BPVB. The blocks were performed in sitting position. Under complete aseptic conditions, Eason and Wyatt technique was used as described [19],[20] Bilateral PVB was performed at the level of T9-T 11 depending on the type of ventral hernia and the planned surgical incision [Figure - 1].

The appropriate levels for the blocks were determined by palpation of the spinous processes [Figure - 1]A. An intervertebral line was drawn at the appropriate levels and the puncture site was marked 2.5cm laterally to the midline on both sides towards the cephalade end of the spinous process of T9­T 11 [Figure - 1]B. The skin was prepared aseptically and each puncture site was infiltrated with 3 mL 2% lidocaine. A 18G epidural needle (Minipack Portex, G18, SIMS Portex trademarks,UK) was inserted at the site of injection [Figure - 1]C. The needle was advanced at 90° to the skin in all planes to strike the transverse process or the head of the rib. It was then directed over the top of the bony structure and advanced slowly no more than 0.5-1.5cm. The technique of loss of resistance to normal saline injection was used to identify the paravertebral space after the needle passed the costotransverse ligament. After encountering the costotransverse ligament, the needle was advanced approximately 0.2 -0.3cm further, no more than that to avoid penetration of the pleura, then an epidural catheter I 8G was introduced in the paravertebral space for no more than 3 cm as to avoid the epidural migration. 3m1 of 0.5 levobupivacaine as a test dose was injected [Figure - 1]D. The same steps was done to contralateral side to end with insertion of an epidural catheter in the appropriate place with a label on each epidural catheter indicated its anatomical place (right and left).

Patients were given supplemental oxygen by facemask and regular standard anesthetic monitors were attached. Depending on patient size, a 0.3 ml/Kg of the local anaesthetic mixture was injected at each epidural catheter [20] . Each 20mL of the local anaesthetic mixture contained lidocaine 2% 6mL, levobupivacaine 13mL with epinephrine 5(gmL-1 and fentanyl 1mL (50µg). The patient was then returned to the supine position, and adequate distribution of; cutaneous anesthesia and the time for block onset was determined by pinprick.

If patients complained of discomfort or showed clinical signs of pain during the operation, incremental small amounts of fentanyl (50-100(µg iv.) with either propofol or midazolam were given. In case of overt failure of the block, the technique was abandoned and converted to GA. Demographic data, type and duration of surgery, the presence of a heart rate <60 or > 120 beats min-1 and blood pressure recording outside 20% of baseline values were registered intra-operatively by blinded observers.

The aim of the study was deliberately not discussed with the ward nursing staff to minimize bias. Postoperative pain at rest was assessed using a visual analogue scale (0 = no pain, 10 =worst possible pain) at predetermined time intervals (every 6h) during the 0-48 h postoperative period and patients scoring >4 were given meperidine (pethidine) lmg.kg-1, plus tenoxicam (telcotil, Roche) 10mg intramuscular (i.m.) for analgesia. In BPVB group, an infusion rate between 5-10 ml of 0.125% levobupivacaine with lug/ml fentanyl started 45 minutes after the start of surgery for postoperative pain relief. The rate was adjusted according to the pain score of the patient to be less than 4 score. The two catheters were removed 48 hours after surgery and the site of insertion was checked for hematoma, bleeding or infection.

The incidence of postoperative nausea and vomiting (PONY) was recorded for 48 hours and to rescue PONY, granisetron (Kytril, Roche) lmg IV was used. An independent observer assessed the intraoperative comfort by asking the patients to give a verbal statement at predetermined events during surgical procedures. In addition, the surgeons were asked to assess the BPVB technique as satisfactory or unsatisfactory. All patients were subjected to three blood samples, the first sample was prior to surgery for evaluation of the liver enzymes, the coagulation status and for measuring the schistosomal titre. The second sample one hour after end of surgery and the third one 24 hours postoperatively.

Statistical analysis: Data are expressed in mean values ± SD and were compared by using a two-sample Student's t-test, Mann­Whitney U-test or X2-test tested as appropriate to detect statistical significance. P<0.05 was considered significant. The calculation of sample size was based on a mean reduction of length of hospital stay from six to three days as indicated by previous studies [23],[24],[25] . Using a confidence level of 95% ((= 0.05) and a power of 90% (B = 0.1) for the desired tests indicated the need for approximately 27 patients in each group. According to dropout rate, the number of patients increased to thirty patients in each group.


   Results   Top


The two study groups were similar with regard to gender, age, weight, height, ASA class and duration of the surgical procedure. The duration of hospital stay was significantly shorter in Group II compared to Group I with a mean (SD) of 7 (1.3) and 4 (1.2) days in Groups I and II, respectively (P <0.05) [Table - 1]. Anesthetized segments by the BPVB were T7-11 in 22 patients and between T 8-10 in 8 patients with 17 minutes onset time with range between 10­25 minutes. The intraoperative haemodynamic recordings were shown in [Table - 2]. Patients in Group II exhibited more stable hemodynamicaly compared with group I (P< 0.05). A significant reduction in the incidence of PONV was found in group II. The PONV rate in group II was only 3.3%, meanwhile, 26.7% of patients in group I suffered from PONV (P<0.05) [Table - 3]. The median maximum VAS for the first (10-24 h) and second (24­48h) postoperative day were 7 (range 0-9) and 6 (0-8) versus 0(0-3) and 1(0-7) in groups I and II respectively. Most of the patients in group I (90%) needed supplemental opioid administration during the first 24 h after operation, and 66.7% also needed supplemental opioid analgesia during the subsequent 24h. The corresponding numbers for group II were significantly lower, being 0% (P<0.001) and 13.3%. Twenty patients in the group II required light sedation during the surgical procedure while ten patients could be managed without additional sedation [Table - 4]. In all cases of BPVB, the surgeons expressed their satisfaction with the intraoperative conditions when specifically questioned regarding this issue. Most patients in group 11 (90%) were comfortable during surgery [Table - 4]. In the remaining three patients, the reason for discomfort was the unexpected need for extension of the surgical incision outside the blocked area. Group II patients could start feeding soon after the end of the surgical procedure (30min to lh after surgery), could help in the transition from the operating table to the regular hospital bed and could ambulate within 2-4 h after the operation. No patient in that group needed extended recovery room stay or admission to the intensive care unit (ICU), whereas all patients in the group I required a recovery room stay of > 45 min and three patients were admitted to ICU due to hemodynamic instability. There was also one postoperative death in the group I (cerebral hepatic encephalopathy) seventh day of surgery. In group II, no patient complained of hematoma, bleeding or infection at the catheter insertion sites [Table - 3].

The preoperative laboratory investigations showed an increase in the liver function enzymes especially AST and ALT with acceptable extended prothrombin time. Schistosomal antibodies were highly positive (titre above 1/64) in 26 patients and weak positive (up to 1/64) in 4 patients in group I, mean while 24 patients had a highly positive titer and 6 patients were weak positive in group II. The weak positive patients were verified by second diagnostic IFT or ELISA tests. However, GSTA levels, in spite of high records over normal range, showed no significant difference increase between the groups and within the same group at different samples readings. AST and ALT readings, in spite of being higher than normal range, showed no significant difference increase compared to both the preoperative readings and the other group readings [Table - 5]


   Discussion   Top


Schistosomiasis affects the physical and health status of the patients leading to liver fibrosis which may end with cirrhosis and failure [2] . Schistosomiasis may be complicated with hepatitis infection leading to advanced hepatic insufficiency and failure [3] . It represents a challenge for anesthesiologists since general anesthesia with inhalational anesthetics may affect the liver cell function integrity [7],[8] The affected schistosoma patients have various risk factors e.g. Liver insufficiency, bleeding tendency, moderate to severe ascites with possible respiratory complications

Various reports have described the effectiveness and advantages associated with the use of unilateral PVB in the perioperative settings. However, to our knowledge, the present study represents the first prospective, blinded, randomized study to evaluate the efficacy and efficiency of the bilateral use of PVB with catheter insertion compared to GA in schistosomal hepatic fibrosis patients subjected to anterior hernia repair. This study showed that the length of hospitalization in patients treated with BPVB was shorter compared with those who received GA. The shorter hospital stay was previously documented by the work of Naja and his colleagues during their work on the PVB [17],[18],[19] They concluded that BPVB was associated with shorter hospital stay 12.3 (SD 1.3) days} in BPVB group compared to general anesthesia group {4.1 (SD3.0) days}. The length of hospital stay is extend in our two groups (four days in BPVB group and seven days in GA group), that is may be due to the different type of patients who had advanced schistosomal liver disease. The decision to discharge the patient was made solely by the surgeon in charge of the patient according to established clinical routine and, thus, the investigators could not influence the decision in any way. The reason for the addition of lidocaine to this mixture is to speed up the onset of the block. Adding epinephrine markedly improved the pain-relieving effect, increased the sensory blockade of levobupivacaine and fentanyl with low nausea and vomiting which could be explained by the (2- agonist action of epinephrine [23] . The rationale for the addition of fentanyl is based on the presence of opioid receptors in the dorsal root ganglion [18] , a structure that most likely will be affected by a PVB. All these advantages facilitate early mobilization

Hemodynamic stability was obviously more in the BPVB group compared to the GA group. Only two patients had a moderate hypotension, which was treated with rapid fluid infusion. This may be explained by migration of the catheters to epidural space. Meanwhile, the local anesthetic, levobupivacaine had a vasoconstrictive effect which augumented by adding epinephrine and fentanyl. Adding the previous drugs allowed the safe use of levobupivacaine with minimal cardiotoxic effect. Robinson and his colleagues stated that fentanyl significantly reduces levobupivacaine requirements for epidural analgesia for labor labor [26] . Further studies are needed for evaluation of the same effect in BPVB technique.

The use of BPVB was also associated with further advantages compared to GA: First, it was associated with superior postoperative pain relief. This effect was not just limited to the expected duration of the regional nerve block but was present during the entire 48-h study period with the use of infusion technique via the catheters. It could be speculated that paravertebral injections of a local anaesthetic mixture containing local anaesthetics plus opioids might be capable of achieving pre-emptive analgesia. PVB as part of a balanced analgesia regimen after thoracotomy represents one of the few reports showing a significant pre-emptive effect, further studies are necessary to substantiate this hypothesis [13],[14],[15],[16] . Second, a significant reduction in PONY was also found in Group II (P< 0.05). This was previously reported especially following breast surgery in patients receiving unilateral PVB together with light sedation compared with GV [15],[16] ) Reduced sensory input from the surgical field and no exposure to either induction agents or volatile anesthetics can be additional factors responsible for the reduced incidence of PONV in group II. Third, satisfactory surgical conditions in group II were noted by most of the surgeons with no complaints as regards that technique. Meanwhile, high patients intraoperative comfort during the various parts of the procedure [Table - 4], together with the fact that 33% of BPVB patients did not require any additional sedation and the rest of the patients only needed minimal supplemental sedation, pointed to the fact that BPVB covered the dermatomes needed to achieve high surgical quality with good patient acceptance. An additional advantage of the bilateral PVB technique was that it avoids the necessity for endotracheal intubation in these patients who had usually weak esophageal sphincter, gastroesophogeal reflux and esophageal varices, thus, the risk of regurgitation and aspiration is less common since consciousness and protective reflexes are preserved throughout the surgical procedure.

Propofol infusion was used in group I instead of inhalational anesthestics because the inhalational anesthetics affect the hepatic function [21] . Levobupivacaine infusion was used as local anesthetic supplemented with epinephrine and fentanyl to reduce the incidence of hypotension which may affect the blood flow to the liver [25] . In addition, the infusion continued in the postoperative period for pain relief.

The disturbance in the hepatocellular integrity was detected by the use of glutathione S transferase alpha (GSTA), a high sensitive marker [19] , in addition to AST, ALT and prothrombin time. Measurement of hepatic GSTA in plasma or serum represents an advance in early recognition of drug-induced liver injury. Because of their assumed central role in the biotransformation of xenobiotics, this group of enzymes attracted attention from biochemists and anesthetists. One of the properties of hepatic GSTA, which may partly explain their great sensitivity as markers of liver damage compared with aminotransferases, is its wide distribution within the liver. GSTA are readily and rapidly released into circulation after hepatic injury: Their shorter half-life (<90 min.) allow early detection of hepatic damage compared with AST(17h) and ALT (47h). Accordingly, the time for blood samples was determined. Murray et al showed a good correlation between GSTA concentration and hepatocellular integrity [7] . They stated that plasma concentration of GSTA provides a sensitive and simple method of investigating the change in hepatic function which occurred after lengthy exposure to halothane but not isoflurane [5] . In addition, Ray et al found that significant temporal changes in GSTA concentration occurred after spinal anesthesia (P < 0.05) [27] . They stated that the liver blood flow is reduced in spinal anesthesia but that was related to systemic hypotension and if hypotension did not occur, or if it was rapidly corrected with ephedrine, liver blood flow is not reduced. Hence, there will be no increase in GSTA concentrations suggesting that liver blood flow was maintained [27].

Our results of AST and ALT readings showed highly significant increase compared to normal range (P< 0.05), however, there were no significant increase when compared to the preoperative levels in the same group and between both groups at different sampling time. GSTA showed the same pattern; highly significant difference of the preoperative readings compared to normal range and no significant difference was detected when compared with other readings between same group or between both groups' readings, indicating that the liver condition of the schistosomal patients was compromised and the techniques used in group I (propofol TIVA) and in group II, (BPVB via catheter with Levobupivacaine local anesthetic plus fentanyl and epinephrine) did not alter the hepatocellular integrity and maintained the cardiovascular stability of these patient and hence maintain the blood flow to the liver [26],[28] .

In conclusion, the results of this study highlighted the superiority of BPVB via catheter over the general anesthesia in patients suffering from chronic schistosomal liver disease and requiring abdominal hernia repair. It was associated with shorter hospital stay and ambulation and better postoperative pain relief. Based on these encouraging results, it is recommended to make use of this technique in such category of patients.

 
   References   Top

1. Warrell DA. Leishmaniasis, malaria and schistosomiasis in Saudi Arabia. Saudi Med J 1993; 14: 203-8.  Back to cited text no. 1    
2. Al-Quorain A, Satti MB, Al-Hamdan et al. Pattern of chronic liver disease in the eastern province of Saudi Arabia: A hospital based clinicopathological study. Tropical and Geographical Medicine 1994; 46: 358-60.  Back to cited text no. 2    
3. Abdel-Wahab ME. Clinical and pathological aspects of schistosomiasis. In: Schistosomiasis in Egypt. Chapter 6, Boca Roca Fl. 1st edition CRC press, 19824.  Back to cited text no. 3    
4. Engels D.,Chitsulo L.,Montresor A. and Savioli L The global epidemiological situation of schistosomiasis and new approaches to control and research. Acta Trop 2002; 82: 139-46.  Back to cited text no. 4    
5. Guangjin S.,Mingdao J,Qiyang L.,HuiX.,Jiangming H and Xiaomei Y.Study on hisopathology, ultrasonography and some special serum enzymes and collagens for 38 advanced patients of schistosomiasis japonica. Acta Trop 2002; 82: 235-46.  Back to cited text no. 5    
6. Strunin L. Pre-operative assessment of the patient with liver dysfunction . Br J Anaesth 1997; 79: 50-52.  Back to cited text no. 6    
7. Murry JM, Phillips AS, Fee JPH. Comparision of the effect of isoflurane and propofol on hepatic glutathione- S-tranferase concentrations during and after prolonged anaesthesia.Br J Anaesth 1994; 72: 599-601.  Back to cited text no. 7    
8. Richardson J, Lonnqvist PA. thoracic paravertebral block. Br J Anaesth 1998; 81: 230­8.  Back to cited text no. 8    
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10. Giesecke K, Hamberger B, Jarnberg PO, Klingstedt C. Paravertebral block during cholecystectomy: effects on circulatory and hormonal responses. Br J Anaesth 1988; 61: 652-6.  Back to cited text no. 10    
11. Richardson J, Sabanathan S, Jones J, et al. A prospective, randomized comparison of preoperative and continuous balanced epidural or paravertebral bupivacaine on post­thoracotomy pain, pulmonary function and stress responses. BJA 1999; 83: 387-2.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]
12. Richardson J, Sabanathan S, Mearns AJ, et al. Efficacy of pre-emptive analgesia and continuous extrapleural intercostal nerve block on post-thoracotomy pain and pulmonary mechanics. J Cardiovasc Surg 1994; 35: 219-28.  Back to cited text no. 12    
13. Richardson J, Sabananthan S, Mearns AJ, Shah RD, Goulden C.A prospective, randomized comparison of interpleural and paravertebral analgesia in thoracic surgery. BJA 1995; 75: 405-8.  Back to cited text no. 13    
14. Richardson J, Sabanathan, Mearns AJ, Sides CS, Goulden C. Post-thoracotomy neuralgia. Pain Clinic 1994; 7:87-97.  Back to cited text no. 14    
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18. Naja Z, El Hassan M, Oweidat M, et al. Paravertebral blockade vs. general anaesthesia or spinal anaesthesia for inguinal hernia repair. Middle East J Anesthesiol 2001; 16: 201-210.  Back to cited text no. 18    
19. Naja Z., Ziade M.F. and Lonnquvist P. Bilateral paravertebral somatic nerve block for ventral hernia repair. European Journal of Anaesthesiology 2002; 19: 197-202.  Back to cited text no. 19    
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25. Pusch F, Freitag H, Weinstabl C, Obwegeser R, Huber E, Wildling E. Single-injection paravertebral block compared to general anaesthesia in breast surgery. Acta Anaesthesiol Scand 1999 43: 770-4.  Back to cited text no. 25  [PUBMED]  [FULLTEXT]
26. Robinson A.P, Lyons G.R., Wilson, Gorton H.J. and Columb M.O. Levobupivacaine for epidural analgesia in labor: The sparing effect of epidural fentanyl. Anesth Analg 2001; 92: 410-4.  Back to cited text no. 26    
27. Ray D.C, Robbins A.G, Howie A.F, Beckett G.J, Drummond G.B. Effect of spinal anaesthesia on plasma concentrations of glutathione S-transferase. BJA 2002; 88: 285-7.  Back to cited text no. 27    
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Correspondence Address:
Haitham Ahmed Abou Zeid
Department of Anesthesia, King Fahad Hospital of the University, Al Khobar
Saudi Arabia
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PMID: 19861829

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