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ORIGINAL ARTICLE
Year : 2018  |  Volume : 12  |  Issue : 2  |  Page : 297-303

Dexmedetomidine in a surgically inserted catheter for transversus abdominis plane block in donor hepatectomy: A prospective randomized controlled study


1 Department of Anesthesia and Intensive Care, Faculty of Medicine, Mansoura University, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Egypt
3 Department of General Surgery, Faculty of Medicine, Mansoura University, Egypt

Correspondence Address:
Dr. Mohamed Adel Aboelela
Faculty of Medicine, Mansoura University, Mansoura
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/sja.SJA_577_17

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Date of Web Publication9-Mar-2018
 

  Abstract 


Background: Transversus abdominis plane (TAP) block is a promising technique for analgesia after abdominal surgery. This prospective, randomized controlled trial assessed the effect of adding dexmedetomidine to bupivacaine in TAP block for donor hepatectomy. We hypothesized that this would improve postoperative morphine consumption and reduce analgesia related complication and inflammation.
Methods: A total of 50 donor hepatectomy were enrolled in this study. Patients divided into two equal groups according to drugs used for TAP block. Group (B) received 20 ml of bupivacaine hydrochloride 0.25%, Group (BD) received 20 ml of bupivacaine hydrochloride 0.25% and 0.3 μg/kg dexmedetomidine, on both sides at the end of surgery and every 8 h for 48 h at right side only through inserted catheter. Primary outcome objective was morphine consumption at first 72 h. Secondary outcome objectives were morphine requirement, numbers of intake, time to first intake, pain score numerical analog scale (NAS), postoperative analgesia related complications, recovery of intestinal motility, and inflammatory markers.
Results: Data were analyzed, rescue morphine analgesia was significantly lower in (BD) group compared with (B) groups as considering total morphine consumption (B 4 ± 1.9, BD 1.5 ± 0.5, P = 0.03), numbers of morphine intake (P = 0.04), morphine requirement (P = 0.03), and first time of analgesia intake (P = 0.04). NAS was significantly lower in group (BD) compared with group (B) group in the first 12 h (NAS 0 - P = 0.001, NAS 1 - P = 0.03). Adding dexmedetomidine improved gut motility, first oral intake without detectable anti-inflammatory effect.
Conclusion: Adding dexmedetomidine to bupivacine in a surgically inserted catheter for TAP block in donor hepatectomy reduced morphine consumption without detectable anti-inflammatory effect.

Keywords: Analgesia; dexmedetomidine; donor hepatectomy; transversus abdominis plane


How to cite this article:
Aboelela MA, Kandeel AR, Elsayed U, Elmorshedi M, Elsarraf W, Elsayed E, Elgawalby A, Sultan AM, Wahab MA, Yassen A. Dexmedetomidine in a surgically inserted catheter for transversus abdominis plane block in donor hepatectomy: A prospective randomized controlled study. Saudi J Anaesth 2018;12:297-303

How to cite this URL:
Aboelela MA, Kandeel AR, Elsayed U, Elmorshedi M, Elsarraf W, Elsayed E, Elgawalby A, Sultan AM, Wahab MA, Yassen A. Dexmedetomidine in a surgically inserted catheter for transversus abdominis plane block in donor hepatectomy: A prospective randomized controlled study. Saudi J Anaesth [serial online] 2018 [cited 2018 Oct 19];12:297-303. Available from: http://www.saudija.org/text.asp?2018/12/2/297/227000




  Introduction Top


Maintaining adequate postoperative analgesia in living related donor hepatectomy is a great concern to avoid several adverse effects related to postoperative pain.[1]

Multiple analgesic modalities have been described for analgesia after donor hepatectomies such as intravenous opioid, nonsteroidal anti-inflammatory drugs (NSAIDs), and epidural analgesia.[2] Opioids while effective at rest, tend to be ineffective in pain relief associated with movements such as coughing and ambulation.[3] Moreover, opioids are associated with different adverse effects such as nausea, vomiting, constipation, sedation, and respiratory depression. The use of NSAIDs as a part of multimodal analgesia after hepatectomy is not popular due to liver insult and blaming for increased bleeding tendency.[4]

Donor hepatectomies alter postoperative drug metabolism and hemostasis leading to transient coagulopathy with elevated INR and reduced platelet count. This is thought to be due to decreased synthetic function of the remnant liver as well as hemodilution and consumption of clotting factors. Postoperative coagulopathy peaks 2–5 days.[5],[6] Despite the potential advantages of epidural analgesia, the risk of significant complication such as an epidural hematoma had led several transplant centers to abandon its use in the healthy donor.[3]

Pain management for this unique patients need to be reassessed.[5] Plus visceral pain, movement-evoked incisional pain is a one of major components of pain experienced in such patients, and the nerves responsible originate from thoracic levels (T6–T10).[7] These nerves lie in a plane between the internal oblique and transversus abdominis muscles, known as the transversus abdominis plane (TAP).[8]

The TAP block technique as a part of multimodal analgesia depends on injection of local anesthetics (LA) into this fascial plane, and hence blocking transmission of the sensory impulses from T6 to T10 which are responsible for somatic pain following abdominal surgeries.[9]

Unfortunately, TAP block is limited to duration effect of administered drugs, so using an infusion catheter to administer LA is an option to prolong the block's duration. Catheter insertion can be done either surgically or ultrasound-guided while many studies documented the safety of ultrasound-guided insertion, postoperative tissue swelling at operative side may render this technique difficult to identify muscle plane.[10] Hence, surgical insertion may be a safe, easy, and certain technique in patients with the abdominal incision.

Adjuvant medications were added to LA to prolong the effect of TAP block. Dexmedetomidine is a selective alpha 2 (α2) adrenergic agonist with analgesic and sedative effects. Its use with bupivacaine either epidurally or intrathecally is associated with prolongation of the LA effect.[2] Anti-inflammatory effect of intravenous dexmedetomidine has been previously reported through inhibiting the production of inflammatory mediators such as tumor necrosis factor-α, interleukin-1 β, interleukin-1 receptor antagonist, and interleukin-6.[11]

To the best of our knowledge, the use of a surgically inserted catheter for TAP block has not been studied in donor hepatectomy in randomized controlled trials. Hence, we suggested that adding dexmedetomidine to bupivacaine at the TAP block will improve the analgesic profile and reduce postoperative analgesia related complication and inflammation.


  Methods Top


After approval of institutional review board, Mansoura faculty of medicine (R/16.04.16), clinical trial registry (clinical trial registry-NCT02708459) and obtaining a written informed consent from all patients, the study was conducted on adults undergoing right donor hepatectomy for liver transplantation in gastroenterology surgical center-Mansoura faculty of medicine, Egypt, from march 2016 to December 2016. Totally 50 patients were enrolled in this study. Exclusion criteria were known allergy to any of the study drugs and patient's refusal for participation. Random number generator with closed envelope technique randomized patients into two groups (25 patients each) based on the postoperative analgesic drugs used for TAP block. A Bupivacaine group (Group B, n = 25) with the injection of bupivacaine hydrochloride 0.25% (Watevacin, segmatic pharmaceuticals) only and dexmedetomidine group (Group BD, n = 25) with the injection of both bupivacaine hydrochloride 0.25% and 0.3 μg/kg dexmedetomidine (Precedex, Hospira, USA).

All donors were subjected to routine preoperative assessment according to our local policy including (history and clinical examination, electrocardiography [ECG], echocardiography, complete blood count, liver function tests, renal function tests, coagulation profile, and C-reactive protein). In the operative suite, patients were connected to monitor (General electric-Datex B850, USA) for monitoring ECG, noninvasive blood pressure (NIBP), oxygen saturation. 18 gauge venous catheter was inserted in the right arm. Premedication included pantoprazole (Zurcal 40 mg, AUG pharma, Spain) and 3 mg midazolam (Midathetic, Amoun pharmaceuticals). In operating room, patients were connected to anesthesia monitor for monitoring of ECG, NIBP, end-tidal co2, and oxygen saturation. Anesthesia was induced using propofol 1–2 mg/kg (Diprivan, Fresenius KABI.), fentanyl 2 μ/kg (fentanyl Hameln, Hameln pharmaceuticals, Germany), Rocuronium 0.6 mg/kg (Esmeron, N. V. organon) was used to facilitate endotracheal intubation. Patients were ventilated using (GE– Datex-Ohmeda Aisys ventilator [USA]) using volume-controlled mode to keep EtCO2 35 ± 2 mmHg. Anesthesia was maintained by inhalation of sevoflurane in 40% oxygen in air mixture and infusion of fentanyl 1 μg/kg/h. Muscle relaxation was maintained by infusion of rocuronium bromide 300 μg/kg/h. A central venous catheter (7.5 gauge Triple lumen) was inserted on the right internal jagular vein using ultrasound guidance.

Surgery for right hepatectomy started with extended right subcostal incision followed by surgical steps to dissect and remove the graft and after peritoneal closure, a 4 F single lumen umbilical catheter (manufactured by ultramed for medical product-Egypt) [Figure 1] was introduced by the surgeon on the operative right side through the transverse limb of the incision in the anatomical plane between internal oblique and transversus abdominis muscles and advanced for 8–10 cm to reach subcostal region under direct visualization of the operator and its proximal end got out from the skin through separate opening near the right end of transverse limb of the incision [Figure 2]. After skin closure on the left side, a bolus volume (20 ml) of the study analgesic drug solution was injected using spinal needle 22 gauge with ultrasound guidance (Toshiba-xario, superficial probe, frequency 7–11) to determine the plane between the internal oblique and the transversus abdominis muscle using subcostal approach for TAP block and another 20 ml of the study drugs solution was injected as a bolus in the TAP catheter at same time. In the intensive care unit, same bolus volume of the study drug solution was injected into the TAP catheter every 8 h for 48 h by one of our anesthesiologist team.
Figure 1: 4 F umblical catheter

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Figure 2: Catheter in place

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Data recording and pain assessment using were done by another intensivest using numerical analog scale (NAS) every 12 h for 72 h postoperatively and on patient request for rescue analgesia which was achieved by an intravenous bolus injection of morphine (Morphine, Misr company pharmaceuticals) 0.01–0.02 mg/kg when NAS score is more than 3.

Hemodynamic data recorded including basal, 30 min posthepatectomy and on skin closure during the operative time and every 12 h for 72 h in the intensive care unit. Operative blood loss, urine output, and fluid input were recorded. Laboratory date (C-reactive protein [CRP], complete blood count, alanine aminotransferase [ALT]), axillary body temperature were measured every 12 h for 72 h postoperatively. The patient is considered feverish if body temperature above 38°C in two readings. Daily morning blood samples were collected for three consecutive postoperative days and analyzed for interlukin-6.

Postoperative morphine requirement, total morphine consumption, time of first rescue analgesic request, morphine request number, postoperative nausea and vomiting, first detection of intestinal motility examined by auscultation of intestinal sound every 4 h, onset of successful oral intake, catheter complication (infection at catheter site by redness, swelling, and tenderness), and wound haematoma were recorded.

Inflammation assessment based on the increased level of interlukin-6, CRP, white blood cells (WBCs), and ALT above normal range and occurrence of fever.

In this trial, we hypothesized that adding dexmedetomidine to bupivacaine for TAP block in donor hepatectomy will reduce morphine consumption and reduce postoperative pain related complication and inflammation. Total morphine consumption was adapted as primary outcome objective of this study, rescue analgesia requirement, numbers of morphine request, first-time morphine intake, inflammation markers, and the postoperative pain related complications were secondary outcome objectives.

Statistical analysis

For sample size calculation, G*Power version 3.1.9.2 was used. Mean postoperative morphine consumption was adopted as a primary variable and power of 80 was achieved accepting an effective size of 30%, if the total sample size of 50 was included in the study (25 patients in each group).

Data were collected, tabulated, and statistically analyzed using SPSS program, version 16 (IBM-International Business Machines Corporation, Armonk, New York, United States).

Continuous data were tested for normality and expressed in mean ± standard deviation if normally distributed, median (interquartile range) if not. Categorical data were presented as proportions. ANOVA test was used to detect the statistical significance between the studied groups considering a P < 0.05 as statistically significant.


  Results Top


Fifty patients included in this study, divided into two equal groups 25 patients in each. Neither patient characteristics nor perioperative data showed any significant differences between the studied groups [Table 1].
Table 1: Patient characteristics and perioperative data of studied groups, group bupivacaine (n=25), group bupivacaine dexmeditomidine (n=25), values are in mean±standard deviation, number and percentage

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Patients' perioperative hemodynamic data are demonstrated in [Table 2] with no significant differences among studied groups.
Table 2: Patients hemodynamics data of studied groups, group bupivacaine (n=25), group bupivacaine dexmeditomidine (n=25), values are in mean±standard deviation

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[Figure 3] demonstrates pain assessment by NAS that was significantly lower in (BD) group compared with (b) group in the first 12 h as NAS 0 (B 7.1 ± 2.4, BD 3.7 ± 2.1, P = 0.001) and NAS 12 (B 6.0 ± 1.4, BD 4.1 ± 1.5, P = 0.03).
Figure 3: Numerical analog scale of the studied groups

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Rescue morphine analgesia presented in [Figure 4] was significantly lower in (BD) group compared with (B) groups as considering rescue analgesia requirement% (B 88%, BD 68%, P = 0.03), total morphine consumption/mg (B 4 ± 1.9, BD 1.5 ± 0.5, P = 0.03), numbers of morphine intake (B 3.5 ± 1.7, BD 1.5 ± 0.3, P = 0.04), and first time of analgesia intake/hour (B 0.0 ± 1.95, BD 0.0 ± 0.9, P = 0.04).
Figure 4: Rescue analgesia morphine of the studied groups

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Postoperative data and complication are presented in [Table 3] showing significant difference in time to bowel motility (B 32.0 ± 10.1, BD 25.6 ± 7.2, P = 0.01) and time to first successful oral intake (B 32.9 ± 10.3, BD 25.6 ± 7.3, P = 0.01) with no significant difference between two groups regarding desaturation, fever, postoperative nausea and vomiting incidence.
Table 3: Postoperative data and complication of studied groups, group bupivacaine (n=25), group bupivacaine dexmeditomidine (n=25), values are in mean±standard deviation and percentage

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Markers of inflammation (CRP, WBCs, and interlukin-6) and liver enzyme (ALT) are presented in [Table 4] shows no significant difference between studied groups.
Table 4: Markers of inflammation and liver enzyme of studied groups, group bupivacaine (n=25), group bupivacaine dexmeditomidine (n=25), values are in mean±standard deviation, median (range)

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  Discussion Top


In this clinical trial, we assessed the efficacy of adding dexmedetomidine to bupivacaine for TAP block through a surgically inserted catheter in living donor hepatectomy as co-analgesic and anti-inflammatory. Fifty living donor were enrolled in this study, the primary objective was total morphine consumption used as rescue analgesia.

We found that adding dexmedetomidine to bupivacaine for TAP block through a surgically inserted catheter in donor hepatectomy is effective in improving analgesic profile, reflected as reduced morphine consumption, less frequency of morphine intake, and prolonged time to first morphine intake. It was also associated with earlier recovery of intestinal motility and successful oral intake, however, we could not prove any anti-inflammatory effect.

Modalities used for postoperative analgesia after donor hepatectomy are not free of complication, patient-controlled IV opioid-associated with many side effects particularly with changed drug metabolism.[4] Transient coagulopathy and altered hemostasis rendering epidural use risky.[3] TAP block is a promising technique as a part of multimodal analgesia either in hepatectomy patients or other patients with abdominal surgeries.

Maeda et al. used ultrasound-guided catheter insertion for continuous subcostal TAP block for analgesia after living liver donation. They compared TAP block using infusion of 0.125% levobupivacaine at 6 ml/h. with IV fentanyl-based analgesia and found that continuous subcostal TAP block seemed to alleviate not only breakthrough pain but also the continuous pain at rest. It decreases Cumulative fentanyl consumption for 48 h (P < 0.01), opioid side effects, and promotes postoperative recovery of the intestine.[12]

Siddiqui and Anandan used four-point TAP block for liver resection and inserted two subcostal catheter with ultrasound guidance to allow 0.1% ropivacine to be infused at a rate 5 ml/h. with a dose limit of 200 mg in total. They found that TAP block can produce effective analgesia for upper abdominal and hepatic surgery, patient was mobilized on postoperative day one and discharged from the Intensive Care Unit the next day.[13]

On the other hand, Griffiths et al. showed that bilateral ultrasound-guided TAP block failed to show any additional benefit to multimodal analgesia in patients undergoing midline laparotomy. This finding contrasts with recent literature and our results. The study group of the Griffith et al. was heterogeneous in terms of age, body mass index, and height of surgical incision. Furthermore differing in type, stage of surgery, and incision from our study.[14]

TAP block through inserted catheter is a recently used technique, catheter insertion can be done either surgically or the US-guided. Many studies demonstrated safety of US-guided catheter insertion,[15] whereas Lancaster and Chadwick, documented a case of liver trauma secondary to ultrasound-guided

TAP block resulted to bleeding and peritonitis. Furthermore, this complication is rare but serious to occur it may result from failure to accurately image the entire needle during the right-sided needle placement, resulting in excessive depth of penetration.[16] Furthermore, the transcutaneous method is unreliable if the identification of muscle plane is difficult such in obese, patients with poor muscular tone and operative swollen tissue even in the presence of US guidance.[10]

Asepsis is more easily attained in open technique,[10] Owen et al., described open technique for TAP block injection in cesarean section patients,[10] Salman et al., used open semi-blind technique in herniorrhaphy patients,[17] Teo et al., used semi-blind technique with the help of laparoscopic camera in laparoscopic nephrectomy patients,[18] all of them proved efficacy of open techniques by improving analgesia, reducing rescue analgesia intake and safety as no complication detected like injury or infection. For these previous reasons, we considered to use open technique for catheter insertion as more safe, easy in performance and confirmed as the operator can see the catheter in plane.

Dexmedetomidine is a selective α2 agonist, has sedative, analgesic properties, and sympatholytic action when used intravenously. Perineural adding dexmedetomidine to bupivacaine improved analgesia and reduced morphine consumption. This may be due to a direct action of the drug as vasoconstriction which slow drugs absorption from a poorly vascularized plane. Other investigators have supported another mechanism of action through α2 adrenoceptors agonist effect rather than vasoconstriction. They contributed that to the direct effect on the peripheral nerve activity or local release of encephalines.[19]

Almarakbi and Kaki found that the addition of dexmedetomidine to bupivacaine in TAP block for hysterectomy patients achieves better local anesthesia and provides better pain control postoperatively. Similar to our study, total morphine consumption was significantly different between studied groups (19 vs. 29 mg/24 h, P < 0.001), VAS score was less in dexmedetomidine group in the first 8 h and lower heart rate in the first 4 h without neurotoxic effects. They also attributed these results to local vasoconstrictor effect of dexmedetomidine that slow the absorption and prolong local anesthetics effect.[1]

This result matching with Luna et al. used dexmedetomidine with ropivacaine in TAP block for hysterectomy patients. Adose of 0.5 μg/kg dexmedetomidine added to 20 ml of 0.3% ropivacaine resulted in reduction of sufentanyl consumption with better postoperative pain control.[20]

Abdelaal et al. agreed with the co-analgesic effect of dexmedetomidine added to levobupivacaine in TAP block for patients with abdominoplasty.[21] In general, we can say that adding dexmedetomidine to local anesthetics in perineural injection prolong action as described by Channabasapp et al.[22] and Agarwal et al.[23]

On the other hand, Ozalp et al. have compared dexmedetomidine-ropivacaine mixture to ropivacaine alone in patient-controlled inter scalene analgesia, and they reported similar pain scores in both groups without any advantageous effect of dexemedetomidine.[24]

In this study, we decided to use perineural dexmedetomidine in a dose 0.3 μg/kg, it is well-known that there are no guidelines for the perineural dose of dexmedetomidine. Many studies used dose of 0.5 μg/kg, some used larger doses up to 1.0 μg/kg but we deal with a different group of patients, hepatectomy of about two-thirds of healthy liver rendering metabolism greatly affected with increased plasma level of adminesterated drugs.[6] Hence, regarding patients safety, we decided to reduce the dose.

We did not find a change in hemodynamics between studied groups, this may be due to slow drug absorption when injected in TAP which is poorly vascularized or due to the small dose used.

On the other hand, ranch or et al., added 1 μic/kg dexmedetomidine to ropivacaine in posttibial nerve block and found a significant decrease in heart rate, blood pressure in 1 hpostoperative.[25] This may be due to the large dose used (triple dose used in our study) or due to changed site of injection as post tibial nerve lying in a highly vascular area.

Li et al., documented in their meta-analysis the anti-inflammatory effect of dexmedetomidine when used intravenously,[26] we could not detect this result when used perineural in TAP block. This may be attributed to changing the way of administration or required dose. To the best of our knowledge, no study documented the anti-inflammatory effect of dexmedetomidine when used perineurally.

An area of limitation in this study was detecting serum level of dexmedetomidine as this effect may be related to systemic absorption of the drug rather than local action, use of infusion technique instead of boluses as it provides superior analgesia, limited number of cases to detect secondry outcomes.


  Conclusion Top


Adding dexmedetomidine to bupivacaine for TAP block via surgically inserted catheter in living donor hepatectomy improved the analgesic profile with reduced pain perception, total rescue analgesia consumption, numbers of intake, and first time to take analgesia. Meanwhile, we could not exhibit any anti-inflammatory impact in this particular group of patients. Further studies for the in-depth assessment of the possible anti-inflammatory effect of dexmedetomidine using larger sample size may add value.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Sukegawa S, Higuchi H, Inoue M, Nagatsuka H, Maeda S, Miyawaki T, et al. Locally injected dexmedetomidine inhibits carrageenin-induced inflammatory responses in the injected region. Anesth Analg 2014;118:473-80.  Back to cited text no. 11
    
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Griffiths JD, Middle JV, Barron FA, Grant SJ, Popham PA, Royse CF, et al. Transversus abdominis plane block does not provide additional benefit to multimodal analgesia in gynecological cancer surgery. Anesth Analg 2010;111:797-801.  Back to cited text no. 14
    
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
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