| Abstract|| |
An ideal anesthetic technique for a renal allograft recipient must ensure hemodynamic stability, enhance graft reperfusion, and provide good postoperative pain relief. Hence, a combined general and epidural anesthesia is preferred. In our clinical practice, it has been observed that in chronically ill end-stage renal disease (ESRD) patients, a bolus injection of epidural local anesthetics invariably necessitated the use of vasopressor agents. Such hemodynamic fluctuations may not be favorable for the graft. A prospective, randomized, double-blind study was conducted on 50 ESRD adults, 18-55 years, scheduled for elective live related kidney transplantation. The patients randomly received either epidural fentanyl (50 μg) and normal saline (10 mL) or epidural fentanyl (50 μg) and bupivacaine (0.5%; 10 mL) followed by standardized general anesthesia. Perioperative hemodynamics and vasopressor requirements were compared with both regimens. Early graft function was assessed by the onset of diuresis after declamping, serial creatinine values, glomerular filtration rate, and 24-hour urine output estimation. In the preoperative period, statistically significant reduction in the mean arterial pressure and the cardiac index occurred in 60% of the patients receiving epidural bupivacaine boluses. These hypotensive episodes required a therapeutic intervention prior to general anesthesia, that is, intravenous mephenteramine (3-6 mg; 9.60 ± 2.32 mg) and crystalloid infusion (189.28 ± 21.29 mL). Intraoperative hemodynamic parameters, surgical blood loss, and transplanted kidney function were comparable between the groups. We concluded that the use of regional anesthetics needed to administered cautiously in renal transplant recipients to maintain hemodynamic parameters.
|How to cite this article:|
Sen I, Thomas S, Arya V K, Minz M. Preinduction hemodynamic fluctuations in renal transplant recipients-Comparison of two combined anesthesia regimens. Saudi J Kidney Dis Transpl 2014;25:1232-9
|How to cite this URL:|
Sen I, Thomas S, Arya V K, Minz M. Preinduction hemodynamic fluctuations in renal transplant recipients-Comparison of two combined anesthesia regimens. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2020 Jun 5];25:1232-9. Available from: http://www.sjkdt.org/text.asp?2014/25/6/1232/144257
| Introduction|| |
Renal transplantation is a well-accepted treatment modality for patients with end-stage renal disease (ESRD).  Organ viability associated with kidney transplantation is a product of the management of the donor, the renal allograft, and the recipient. An adequate anesthetic technique should achieve hemodynamic stability, enhance perfusion of the transplanted kidney, and counteract the increased concentration of circulating catecholamines in patients with chronic renal failure (CRF). ,,, As renal painful stimuli are conducted multisegmentally through the spinal nerves (T10 to L1) and the vagus nerve, a combination of general with regional anesthesia is preferred to regional anesthesia alone. ,, The combined technique provides ambient conditions for surgical intervention and adequate postoperative pain relief, without respiratory compromise. However, in our clinical practice, it has been observed that in chronically ill end-stage renal disease patients, a bolus injection of epidural local anesthetics invariably requires the use of vasopressor agents to manage the hemodynamic fluctuations, which are not favorable for the allografts.
We aimed in this randomized controlled trial to compare the effect of general anesthesia in addition to epidural fentanyl and bupivacaine or epidural fentanyl without bupivacaine used for the operation of kidney transplantation. Perioperative hemodynamics, pain relief, and early renal graft function were evaluated.
| Materials and Methods|| |
This is a prospective randomized double-blind study of 50 end-stage renal disease (ESRD) patients aged 18-55 years, who underwent elective live related transplant surgery between June 2008 and November 2009. All the patients were estimated according to the American Society of Anesthesiology (ASA), as class II/III. The study was approved by the Institutional Ethical Committee. All the patients were thoroughly assessed clinically besides undergoing hematological, biochemical, and radiological investigations. Patients with a history of allergy to study drugs, compensated or decompensated myocardial dysfunction, contraindication to epidural anesthesia or patients who had accidental dural puncture were excluded from the study. All the participants underwent hemodialysis, one day prior to surgery, as per the Institutional protocol for kidney transplantation. Premedication advised was oral alprazolam (0.5 mg), tablet ranitidine (150 mg), and metaclopromide (10 mg). Anti-hypertensive and immunosuppressant therapy was administered with caution and attention paid to the drug interactions and the patient's hemodynamic status after the last dialysis.
In the Operating Room, electrocardiography (ECG) monitoring, arterial oxygen saturation (SpO 2 ), and Bispectral Index (BIS) monitoring were initiated. The limb with arteriovenous fistula was not used for peripheral venous access or invasive blood pressure monitoring. Maintenance 2 mL/kg/hour normal saline infusion was started. Fentanyl 1 μg/kg was administered intravenously for mild sedation. Supplemental oxygen therapy was initiated using ventimask (FiO 2 - 0.5). A 20 G arterial cannula was inserted into the radial artery under local infiltration for continuous blood pressure and cardiac output (CO) monitoring (Edwards life-sciences flotrac sensor and vigileo monitor). , A double lumen central venous catheter was inserted into the right internal jugular vein (RIJV) under local infiltration, and baseline central venous pressure (CVP) was measured. The mean of the first three recordings of monitored hemodynamic parameters at five minute intervals of measurement, after the patient was shifted to the Operation Room was considered as baseline values for subsequent comparison. Then, an 18 G epidural catheter was placed in the T12 - L1 epidural space in the left lateral position under aseptic precautions. Correct placement of the catheter was confirmed by injecting a test dose of 3 mL of 2% lignocaine with adrenaline 1:200,000. Heart rate (HR), SpO 2 , systolic and diastolic blood pressure (SBP, DBP), mean arterial pressure (MAP), CVP, and cardiac output were noted just before giving the epidural test dose. A record was kept of changes in all these parameters at five-minute intervals.
The patients were randomly allocated to receive either epidural fentanyl 50 μg in 10 mL of normal saline and standardized general anesthesia (Group A) or epidural fentanyl 50 μg in 10 mL of bupivacaine 0.5% in incremental doses followed by standardized general anesthesia (Group B). Any fall in SBP <90 mm Hg or fall in MAP >20% was considered as hypotension and managed by intravenous fluids, vasopressors (mephenteramine 3-6 mg intravenous boluses) or inotropic (dopamine, dobutamine) support.
After establishing hemodynamic stabilization, general anesthesia was instituted in the two groups using intravenous propofol (1.5-2.5 mg/kg) titrated to effect. Neuromuscular monitoring was commenced using the TOF module, and intravenous atracurium besylate injection (0.5 mg/kg) was administered to facilitate endotracheal intubation. Subsequently, intermittent positive pressure ventilation was commenced with a mixture of 50% nitrous oxide in oxygen and isoflurane 0.5-1%, using a closed circuit with a circle absorber. The ventilation was adjusted to maintain end-tidal carbon dioxide (EtCO 2 ) between 35 and 40 mm Hg throughout the procedure. Adequate depth of anesthesia was ensured by maintaining BIS values between 50 ± 10. A TOF count of two or more was an indication for giving atracurium 0.1 mg/kg.
In all the patients, the CVP was gradually increased to 15 mm Hg using colloids (2-4 mL/kg of 20% albumin) and crystalloids, and it was maintained until revascularization of the allograft was completed. Blood transfusion was considered according to the hemodynamic parameters, estimated blood loss, and serum hemoglobin levels. Furosemide 2 mg/kg, hydro-cortisone 10 mg/kg, and 20% mannitol 100 mL were injected intravenously in all the patients before the reperfusion of the grafted kidney. Target hemodynamics of mean BP >85 mm Hg and CVP of 12-15 mm Hg were maintained during and after declamping. Once graft diuresis was established, intravenous fluid therapy was continued to maintain CVP 12-15 mm Hg. In case of no urine output, fluid administration was restricted. Intra-operative inadequate analgesia, as evidenced by an increase in systolic blood pressure and/or heart rate, by >20% of the baseline values in response to surgical stimulus, was treated with a bolus of fentanyl (0.5 μg/kg) in both groups. The total dose of vasoconstrictors/inotropes used to maintain the perioperative hemodynamics was recorded. Intravenous ondansetron (0.1 mg/kg) was administered half-an-hour before the expected time of completion of the surgery. At the end of surgery, the anesthesia was reversed with neostigmine (0.05 mg/kg) and glycopyrolate (0.01 mg/kg). The patients were extubated on meeting the standard criteria for extubation and were shifted to the kidney transplant Intensive Care Unit. The hart rate, respiratory rate, EKG, non-invasive blood pressure, and SpO 2 were continuously monitored.
Postoperative analgesia was provided with 0.125% of bupivacaine, 4-8 mL/hour in titrated doses. The events in the postoperative Recovery Room were recorded every four hours by an anesthesiologist, who was not aware of the patients' group assignments. The side effects attributable to the study drug were noted. The epidural catheter was removed when the VAS score was <3 for 12 hours.
The postoperative graft function was assessed by the onset of diuresis after the reperfusion of the allografts and the total urine output during the first 24 hours. The GFR, as depicted by creatinine clearance, was calculated to assess the graft function. , The collected data were compared with the baseline values in each group between the two groups.
| Statistical Analysis|| |
The sample size was calculated based on the previous studies. , To detect a 50% decrease in the incidence of hemodynamic side effects, a minimum of 23 patients per group were required to ensure adequate power to the study, with of 0.05 (confidence interval 95%) and of 0.1 (power of 90%). Therefore, 25 patients were studied in each group. The patient characteristics were analyzed with the Chi-square test for nominal data. Parametric data (age, height, weight) were analyzed using the independent sample t -test. Non-parametric data were analyzed using the Mann Whitney-U test. Continuous data such as heart rate and blood pressure were analyzed by the repeated measure analysis of variance (ANOVA) followed by one-way ANOVA. Quantitative data were expressed as the mean ± SD range. Categorical data were expressed as number (%) or median. P-value of <0.05 was considered statistically significant. The data were analyzed with the Statistical Package for Social Studies (SPSS) for windows 14, Chicago, IL, USA.
| Results|| |
The recipients' demographic characteristics and intraoperative graft characteristics (warm ischemic time, cold ischemic time, and time of onset of diuresis after declamping) were comparable in both the groups [Table 1]. The hemodynamic variability was measured using heart rate (HR), mean arterial pressure (MAP), and cardiac index (CI). There was a statistically significant fall in MAP and CI 15 and 20 minutes after administration of the epidural drug in 60% of group B patients versus none in group A [Figure 1]. This transient hypotension was managed with mephenteramine boluses (3-6 mg, and a mean of 9.60 ± 2.32 mg) and crystalloid infusion (189 ± 21.3 mL). The intraoperative hemodynamic variables remained stable in both the groups. Although the heart rate, MAP and CI were comparatively low in group B, the values were not statistically significant when compared to the baseline in group B [Figure 1]. The patients in group A required more intravenous fentanyl and atracurium to maintain adequate anesthesia compared to group B. The intraoperative blood loss was less in group B versus group A. The fluid and colloid requirements were comparable in the two groups. The immediate graft function as assessed by time of onset of diuresis, postoperative creatinine, calculated GFR, and total urine output in the first 24 hours were comparable in both groups [Table 1].
|Figure 1: Comparison of the means of heart rate, systolic blood pressure, and cardiac index between the two groups in the preoperative and intraoperative periods|
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|Table 1: Demographic characteristics and perioperative data of the study patients.|
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| Discussion|| |
The main objective of the present study was to find out whether the use of epidural local anesthetic boluses was safe in renal transplant recipients and whether the vasopressor drugs used to maintain the target hemodynamic parameters had any adverse outcome on graft function. There are studies showing that if high vasopressor support is given to maintain hemodynamics in recipients, the grafted kidney microcirculation may be adversely affected. ,, Significant hypotension (fall in MAP >20% of baseline) was observed in 60% patients after epidural bupivacaine and fentanyl bolus administration necessitating the use of mephenteramine and rapid infusion of crystalloids. A significant fall in BP was due to sympathetic blockade by epidural bupivacaine. On induction of general anesthesia, again there was reduction in MAP and cardiac index compared to the baseline in both the groups. Kasaba et al. observed that hypotensive effects of propofol were additive to those of epidural anesthesia, resulting in decrease in MAP at the induction of anesthesia. In kidney transplant recipients severe dehydration due to recent dialysis, increased sensitivity to anesthetic agents, and long-term treatment with anti-hypertensives agents can further affect the hemodynamics. Following laryngoscopy and intubation MAP increased toward the baseline in group A and B. Analysis of hemodynamic response to laryngoscopy and endotracheal intubation as assessed by a rise in MAP revealed a mean rise of 12.12 ± 9.90 mm Hg in group A as compared to 10.2 ± 6.1 mm Hg in group B. Despite stimulation of laryngoscopy at a comparable depth of anesthesia, the MAP and cardiac index were lower in group B as compared to group A, although this was statistically insignificant (P value 0.75). This finding is consistent with the studies showing blunting of intubation response in patients receiving epidural and general anesthesia. ,
The incidence of hypotension in the present study was contrary to findings of earlier studies using epidural anesthesia. Hadimioglu et al  and Akpek et al  did not report any case of hypotension after epidural administration of the local anesthetics. However, Bhosale et al  reported 6% incidence of hypotension in their prospective study in renal transplant surgery. In the present study, continuous hemodynamic monitoring was initiated before the administration of the epidural drug and there was transient, but significant hypotension in group B, in 60% of the patients after epidural administration of bupivacaine with fentanyl in incremental doses. This contrary finding may be due to the fact that in our study, hypotension was described as any fall in MAP to >20% of the baseline, but the previous authors , have described any fall in MAP to >30% of the baseline as hypotension. Our findings are consistent with the retrospective study of Hirata et al  in which the authors found a 51% incidence of hypotension (fall in MAP >30%) in patients receiving epidural local anesthesia along with general anesthesia.
In previous studies, , prophylactic low-dose dopamine (LDD) infusion was started to maintain the perfusion pressure of the grafted kidney. LDD (2-3 μg/kg) stimulates dopaminergic (DA 2 ) receptors in the kidney vasculature and causes vasodilatation, and it was previously recommended for increasing urine output. Dauri et al  compared the combined general and epidural anesthesia with general anesthesia alone. They concluded that the dopamine infusion rate required to maintain the perfusion pressure was higher in the combined anesthesia group. Akpek et al  also started dopamine infusion soon after the epidural drug was administered. This may be the reason that no case of hypotension was reported. Ciapetti et al  observed that LDD neither improved the kidney function during the postoperative period nor the short-term outcomes, but was associated with an increased heart rate, ICU length of stay, and sixth-month mortality. Kadieva et al  also reported that peri-operative infusion of dopamine at 3 μg/kg/ minute was not beneficial in the transplanted kidney, and maintenance of perfusion pressure by a generous administration of intravenous fluids to permit adequate renal blood flow was found to be more important for achieving good graft function. In our study, the transient hypotension in group B could be managed with intravenous boluses of mephenteramine, an indirectly acting synthetic non-catecholamine drug, and none of the participants required infusion of any other inotrope or vasopressor agent.
In our study and during the entire intra-operative period, the MAP and the CI remained stable, and the heart rate changes were comparatively less in group B, although the hemodynamic parameters were on the lower side compared to group A. The intraoperative requirement of supplemental doses of neuromuscular agents and fentanyl was significantly reduced in group B. These findings are consistent with other studies showing stable intra-operative hemodynamics in combined epidural and general anesthesia compared to general anesthesia alone.,,, The estimated blood loss was less in group B, and this can be attributed to the lower blood pressure in group B. During the declamping stage, there is a release of acid metabolites, prostaglandins, activated complements, cold perfusate of the grafted kidney, and myocardial depressant factors. After declamping, the MAP decreased in all the patients; however, the fall was not significant in both the groups. All the graft recipients received adequate hydration to maintain the CVP of 12-15 mm Hg as recommended by Carlier and Luciani et al.
A literature review reveals poor outcome of grafted kidney with hypovolemia and hypotension preceding revascularization. Pouttu et al concluded that arterial hypotension before and just after revascularization of allografts may predispose to delayed onset of allograft function. In our study, the hypotension that occurred in Group B was transient and was promptly corrected by boluses of mephenteramine. These findings are consistent with Hirata et al, who suggested that the prognostic indicators of immediate graft function are: Live donor graft, adequate hydration (80 mL/kg crystalloids) and hemodynamic stability. In our study, none of the patients had adverse effects related to the drugs used in the study, that is, epidural bupivacaine and fentanyl. Basta et al reported a case of epidural hematoma following epidural catheter placement, in a patient with chronic renal failure (CRF). None of our enrolled patients had any anesthetic or surgical procedure-related complication.
In conclusion, the early kidney allograft function was not affected by the anesthetic technique as long as the perioperative hemodynamics were maintained. However, the preoperative hemodynamics were significantly affected by epidural bupivacaine bolus, necessitating therapeutic intervention prior to general anesthesia. Accordingly, regional anesthetics need to be administered cautiously as slow variable rate infusions, titrated to maintain the hemodynamic parameters.
Conflict of Interest: None.
Funding/Support: No financial or material support was received for the research and work conducted in this study by any funding source.
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Dr. Indu Sen
Department of Anesthesia and Intensive Care, Postgraduate Institute of Medical Education and Research, Chandigarh