Negi 2014
Negi 2014
Negi 2014
Abstract
Background: Ideal anesthetic technique for renal allograft recipients should provide
hemodynamic stability, optimum graft reperfusion and adequate analgesia. Balanced anesthesia
is preferred because renal nociception is conducted multi-segmentally and chronically ill ESRD
patients have labile psychological profile. Present study compared the efficacy of dexmedetomidine
with fentanyl administered via intravenous and epidural route before induction of general anesthesia.
Methods: Prospective, double blind randomized study, recruited sixty hemo-dynamically
stable ESRD adults, 18-55 years, scheduled for elective live related renal transplantation. Patients
randomly received intravenous dexmedetomidine 0.5 µg/kg followed by epidural dexmedetomidine
0.5 µg/kg alongwith 5ml;0.25% ropivacaine or intravenous fentanyl 1 µg/kg followed by
epiduralfentanyl 1 µg/kg alongwith 5ml;0.25% ropivacaine. All patients received standardized
general anaesthesia and continuous epidural ropivacaine 0.25%; 4-8 ml/hr. Preoperative sedation,
peri-operative haemodynamics, end tidal anaesthetic agent requirement, peri-operative fluid
requirement, need for vasopressors, blood loss and early graft function was assessed.
Results: 80% patients receiving intravenous dexmedetomidine did not require rescue
midazolam for achieving satisfactory sedation before induction of general anaesthesia.
Dexmedetomidine significantly reduced propofol and end tidal inhalational agents requirement and
need for rescue analgesics. Early renal graft function (onset time of diuresis after declamping, 24
hours urine output and serum creatinine levels) was comparable. There were no adverse sequelae.
Conclusion: Dexmedetomidine-based anaesthetic regimen versus fentanyl-based
anaesthesia provided appropriate anxiolysis and analgesia for conducting invasive procedures and
subsequent epidural administration of these agents reduced anaesthetic requirement and prolonged
postoperative analgesia without compromising hemodynamics and respiratory parameters. Further
dose finding studies can be conducted in kidney transplant recipients.
Peri-operative management of renal allograft recipient should assure hemodynamic stability,
enhance graft reperfusion and provide good post- respiratory parameters in end-stage renal disease
operative pain relief1-,3. Every effort is made to choose patients undergoing live-related kidney transplant
the right techniques as well as pharmacological agents surgery.
which facilitate proper functioning of the newly
transplanted organ4,5. Combined general and regional Methods
anesthesia has been preferred considering that renal
nociception is conducted multi-segmentally and
This prospective, double blind randomized trial,
chronically ill ESRD patients have labile psychological enrolled sixty ASA physical status II or III adults,
profile6,7. Epidural anesthesia provides dynamic pain either gender, 18-55 years suffering from end stage
relief, permits early extubation and a better response renal disease. Research ethics committee approval
to the stress of anesthesia and surgery. However, large and informed written consent was taken. Patients with
volumes of local anesthetics (LA) administered via drug allergy, compensated/decompensated myocardial
neuraxial route can have deleterious hemodynamic insufficiencies, coagulation abnormalities or accidental
consequences with associated risk of LA toxicity. dural puncture were excluded. Premedication consisted
Although, Ropivacaine has low risk of cardio- of oral alprazolam 0.25 mg and ranitidine 150 mg
vascular and central nervous system toxicity and a administered the night before surgery. Preoperative
lesser propensity for motor blockade8. Traditionally, monitoring included: electrocardiography (ECG),
opioids have been used as neuraxial adjuvants to baseline heart rate, respiratory rate, noninvasive
reduce the dose of local anesthetics and improve the blood pressure (NIBP), arterial oxygen saturation
quality of peri-operative analgesia9. However, there (SpO2), and bispectral index (BIS). The mean of
is always a possibility of urinary retention, nausea, first three recordings of hemodynamic parameters
vomiting, pruritis and respiratory depression with at 5 min interval taken after the patient was shifted
these agents10. The incidence of motor blockade after to the operation theatre were considered as the
epidural analgesia with amide local anesthetics (LA) baseline values. A 16 G cannula was secured in
and opioids is approximately 4-12%, which defeats the a peripheral vein normal and saline infusion was
novel purpose of appropriate pain relief9. started at 2 ml/kg/hour. The limb with arterio-
Dexmedetomidine, an α2-adrenergic agonist venous fistula was not used for peripheral venous
has sedative, anxiolytic, and anesthetic sparing access and invasive pressure monitoring.
properties. The anti-nociceptive properties of the drug Patients were randomized using computer
has been demonstrated in various trials where it was generated permuted block into two groups (randomized
administered via systemic, intrathecal, perineural blocks of 6 patients in a 1:1 ratio using sealed
or intra-articular routes11-15. Compared to fentanyl, envelopes). Group F patients (n=30) received 1 µg/
dexmedetomidine has been reported to induce sedation kg fentanyl infusion diluted to 20ml intravenous fluid
without affecting the respiratory status. However, over 10 minutes before induction of anesthesia and
efficacy of dexmedetomidine in renal transplant 1 µg/kg fentanyl in combination with 5ml of 0.25%
surgery has not been evaluated. Therefore, the present ropivacaine (total volume 8ml ) via epidural route
study was planned to compare dexmedetomidine after insertion of epidural catheter. Group D patients
and fentanyl administered via both intravenous and (n = 30) received 0.5 µg/kg dexmedetomidine infusion
epidural route prior to induction of anesthesia. diluted to 20 ml intravenous solution over 10 minutes
Our hypothesis is that preinduction intravenous before induction of anesthesia, followed by 0.5 µg/kg
dexmedetomidine infusion will provide anxiolysis dexmedetomidine in combination with 5ml of 0.25%
and analgesia for central venous line and epidural ropivacaine by epidural route (total volume 8 ml).
catheter insertions and its subsequent administration A 20 G arterial canula was inserted in the
via epidural route alongwith ropivacaine will reduce radial artery under local infiltration for continuous
intraoperative anesthetic requirement and prolong blood pressure monitoring. A double lumen central
postoperative analgesia without compromising venous catheter was inserted in to internal jugular
BALANCED ANESTHESIA FOR KIDNEY RECIPIENTS
551
vein (IJV) under local infiltration. Subsequently, In case of poor graft function (no urine output)
under aseptic precaution 18G epidural catheter fluid administration was restricted. The total dose
was placed in T12-L1 space with patient in left of vasoconstrictors/ ionotropes used to maintain
lateral position. Correct placement of catheter was perioperative hemodynamics were noted. Intra
confirmed by injecting epidural test dose (3ml 2% venous ondansetron (0.1 mg/kg) was administered
lignocaine with adrenaline 5µg/ml). The epidural half an hour before the expected time of completion
study solutions were prepared by an uninvolved of the surgery. At end of surgery patient was
anesthesiologist according to written instructions reversed with neostigmine (0.05 mg/kg) and
on sealed envelopes. The solution (8ml) was atropine (0.02 mg/kg)/ glycopyrolate (0.01 mg/
infused over 10 minutes via epidural route. This kg) and extubated on meeting the standard criteria
was followed by maintenance infusion of 0.2% for extubation. They were shifted to post renal
ropivacaine at4ml-8ml/hr administered epidurally. transplant care unit as per the institutional protocol
where hourly hemodynamic parameters were recorded
Hypotension was defined as systolic blood
for 24 hrs. For postoperative pain relief, 4-8 ml/hr
pressure (SBP) ˂90 mmHg or a greater than 20% drop
of 0.2% ropivacaine infusion was used. If VAS was
in mean arterial pressure (MAP) and managed with
>4, first rescue analgesic with intravenous tramadol
intravenous fluid administration to maintain CVP 12-
50 mg was used. For the patients not relieved with IV
15 mmHg. If MAP remained low despite adequate
tramadol morphine 3mg was given.
fluid infusion, vasoconstrictor (mephenteramine
3-6 mg intravenous boluses) or ionotropic support The level of sedation was assessed by the
was instituted to maintain hemodynamic parameters Modified Observers Assessment of Alertness/
within 20% of the baseline values. Sedation Score (OAA/S)16. The intensity of pain
(assessed by a linear Visual Analog Scale)17 and BIS
General anesthetic technique consisted of
values were noted every 5 minutes till the induction
intravenous propofol, atracurium and a mixture of
of anesthesia. Dose of intravenous propofol needed
O2, N2O and isoflurane titrated to BIS value between
for loss of conciousness was also noted.
40-60. Endotracheal intubation was facilitated by
IV atracurium 0.5 mg/kg when TOF count was zero.
After intubation, intermittent positive pressure Statistical Analysis
ventilation was commenced with a mixture of 50%
nitrous oxide in oxygen and isoflurane, using a ANOVA with post-hoc significance, Chi-square
closed circuit with a circle absorber. Ventilation test and Fisher’s exact test were used as appropriate.
was adjusted to maintain end-tidal carbon dioxide Value of P<0.05 was considered significant and P<0.001
(EtCO2) between 35-40mm Hg. A TOF count of 2 as highly significant. The sample size was calculated
or more was an indication for giving atracurium based on previous study7 employing epidural
0.1mg/kg IV. Total dose of atracurium consumption anesthesia with local anesthetic for renal transplant
was noted. In all the patients, CVP was gradually surgery. To detect a 50% decrease in the incidence
build up to 15 mmHg by crystalloids up to 50 ml/ of rescue analgesic requirement a minimum of 28
kg and colloids (2-4 ml/kg; 20% albumin) until patients per group were required to ensure adequate
revascularization. Intravenous frusemide 2 mg/kg, power of the study with α of 0.05 (confidence interval
hydrocortisone 10 mg/kg and 20% mannitol 2 ml/ 95%) and β of 0.1 (power of 90%).
kg was given to all patients before reperfusion
of grafted kidney. Target hemodynamics of mean Results
BP> 85 mmHg, systolic BP> 135 mm of Hg and
CVP of 12-15 mm of Hg were maintained during The demographic profile of both groups was
and after declamping. Blood transfusion was comparable (Table 1). The baseline hemodynamic
considered according to hemodynamic parameters, parameters were comparable in both the groups.
estimated blood loss and serum hemoglobin levels. Observers Assessment of Alertness and Sedation
M.E.J. ANESTH 22 (6), 2014
552 Negi S. et. al
Table 1
The demographic profile of all the patients
THE DEMOGRAPHIC Data
Table 2
Perioperative characteristics of the patients of both the groups
PERIOPERATIVE CHARACTERISTICS
Score noted at 5 minutes interval for 30 minutes after of these two study drugs were chosen. For the same
giving the intravenous drug in both the groups. OAAS reasons, variable rate local anesthetic epidural
of 4 was achieved in 25 patients in Group D after 10 infusion was administered periopeatively ie 0.25%
minutes. However, in Group F only 4 patients achieved ropivacaine at 4-8 ml/hour to titrate MAP within 20%
OASS of 4. The Rest of the patients required injection of the baseline values. Both the anesthetic regimens
of midazolam (1 mg iv). Between groups OAA/S was provided satisfactory anesthesia, but dexmedetomidine
significantly better in group D versus group F (p<0.05). group proved to be a better alternative with less
Induction dose of propofol for hypnosis and requirement of intraoperative anaethetic agents and
achieving BIS value 40 – 60, was significantly lower postoperative rescue analgesics.
in Group D as compared to Group F (p<0.05). EtAA ESRD patients frequently have marked swings
requirement was significantly lower in Group D as in BP during surgery (±30%) and exaggerated
compared to Group F (p<0.05). responses to induction, laryngoscopy, intubation,
A total 27 patients in Group F received injection declamping and extubation21. This is because of
tramadol as compared to only 8 patients in Group preoperative dialysis induced dehydration, increased
D for VAS > 4. In Group F, 18 patients received sensitivity to anesthetics and/or long-term usage
injection morphine as second rescue analgesic versus of anti hypertensives. Therefore, a concern about
4 patients in Group D (p<0.05).Time for maintaining haemodynamic instability has been raised when
adequate analgesia without the need for tramadol was general anaesthesia is administered alongwith central
significantly longer in group D. neuraxial blockade18. In previous studies, prophylactic
Early graft function was assessed by onset of low dose dopamine infusion has been used to maintain
diuresis after declamping, hourly urine output, serum perfusion pressure of the grafted kidney. Bhosale et
creatinine levels and glomerular filteration rate (GFR) al22 reported 6% incidence of hypotension in their
estimation in the first 24 hours.Values were comparable prospective study involving CSEA in renal transplant
in both the groups (p > 0.05). Both the groups did not surgery. Dauri et al23 compared combined general and
differ in terms of post operative nausea, vomiting, epidural anaesthesia with general anaesthesia. No case
shivering and headache. Patients in both the groups of hypotension was reported though the dopamine
received epidural infusion of 0.2% of ropivacaine infusion rate required to maintain perfusion pressure
at the rate of 4-8ml/hr in the post operative period. was higher in the combined group. Akpek al5 started
The epidural catheter was removed when VAS was dopamine infusion soon after the epidural drug was
consistently less than 4 for 12 hours. All the patients administered to maintain adequate perfusion pressures.
were discharged from the transplant unit on the 6th This may be the reason that no case of hypotension
or 7th postoperative day. There were no readmissions. was reported.
Literature reveals that high vasopressor support
Discussion required for the maintainenace of perioperative
haemodynamics can adversely affect micro
In the present study, combination of general circulation of the grafted kidney19,20. Therefore, it has
anesthesia alongwith continuous epidural ropivacaine been commented that vasoconstrictors with strong
infusion was used for live-related renal transplant α-adrenergic effects, such as phenylephrine, should be
surgery. We also used a fixed dose of two different drugs of last resort, Several animal models have also
adjuvants ie fentanyl versus dexmedetomidine via demonstrated that vessels in the transplanted organs are
intravenous and epidural routes prior to induction of more sensitive to sympathomimetics24,25. Therefore, it
general anaethesia. Both these adjuvants alongwith is worthwhile to find out ideal anesthetic regimens.
standard anaesthesia, provided stable hemodynamics Low dose epidural ropivacaine is being preferred
and optimum intraoperative analgesia. Considering because it is less cardiotoxic, provides better analgesia
frequent reports of labile hemodynamic profile of without motor blockade. Addition of neuraxial
ESRD patients18-20, fixed and relatively lower doses adjuvants like opioids and alpha-2 receptor agonists
M.E.J. ANESTH 22 (6), 2014
554 Negi S. et. al
Fig. 1
Consort diagram of patients enrolled for the study
further improve the quality of peri-operative analgesia fusion surgery reduced propofol infusion requirements
due to sedative, anxiolytic, and local anesthetic sparing with less effect on hemodynamics. We also observed
properties9,11,12,13,26 Asano T et al27 observed in an that induction dose of propofol required in Group
animal study that anti-nociceptive efficacy of epidural D was significantly lower as compared to Group F.
dexmedetomidine is approximately five times more Intraoperative EtAA requirement for maintaining BIS
compared to its systemic administration. Salgado P value within 40-60 was also lower in Group D.
et al28 found that epidural dexmedetomidine does All the graft recipients received adequate
not affect onset time or upper level of anesthesia (p hydration to maintain CVP of 12-15mm of Hg. Intra
> 0.05) moreover it prolongs block duration time (p operative fluid requirements (crystalloid and colloid)
< 0.05) and postoperative analgesia (p < 0.05), and to maintain CVP was comparable in both the groups.
also results in a more intense analgesia (p < 0.05). Carlier32 and Luciani33 et al. The authors have emphasize
Superiority of epidural dexmedetomidine has been upon the importance of maximal hydration and
proved in an orthopedic study29. These findings were maintenance of adequate haemodynamic parameters at
confirmed in the present study in ESRD patients. the time of reperfusion for the development of early
Kasaba et al.30 observed that hypotensive effects of diuresis and prophylaxis of acute tubular necrosis in
propofol are additive to epidural anaesthesia, resulting the immediate postoperative period. Kadieva et al34
in significant decrease in MAP. Ngwenyama N et al.31 reported that maintenance of perfusion pressure by
has commented that concomitant use of intravenous generous administration of intravenous fluids to permit
dexmedetomidine in patients undergoing spinal adequate renal blood flow was more important than
BALANCED ANESTHESIA FOR KIDNEY RECIPIENTS
555
perioperative dopamine infusion in achieving graft in Group D.None of the patients had adverse effects
function and survival. During declamping there is a related to the study drugs, anaesthetics used or surgery.
release of acid metabolites, prostaglandins, activated Opioid related urinary retention, pruritis, or respiratory
complements, cold perfusate of grafted kidney and depression did not occur with the dose of fentanyl
myocardial depressant factor35. After eclamping the used. Undue bradycardia did not occur with the single
MAP decreased in all the patients. However, the fall dose dexmedetomidineadministered via parenteral
was not significant in both the groups. Akpek et al36 in and epidural route. None of the patients had any
their prospective study comparing general anaesthesia cardiovascular or neurological side effects due to local
and epidural anaesthesia for renal transplant recipients anaesthetics. There was no accidental dural puncture,
found no difference in the immediate postoperative There was no case of epidural hematoma, neurological
graft function as determined by biochemical markers deficits, hyperacute graft rejection, excessive bleeding,
and DTPA scan. Early graft function was assessed anuria, injury to bowel or other vascular structures.
by onset of diuresis after declamping, post operative
Considering the paucity of published data in
serum creatinine and urine output estimation at hourly
ESRD patients, we preferred to use fixed single dose
intervals for first twenty four hours. These parameters
of dexmedetomidine and infusion was not continued
were comparable in both the study groups. Warm and
intraoperatively or postoperatively. Frumento37 et al
cold ischaemic time and time of onset of diuresis was
found that dexmedetomidine infusion administered as
comparable in both the groups. The estimated blood
a supplement to epidural analgesia induces diuresis in
loss didnot differ amongst groups. Postoperatively
post-thoracotomy patients with normal preoperative
analgesia as assessed using visual analogue scale
renal function and undergoing fluid restriction. In the
(VAS) scores revealed longer and better pain relief
Fig. 2
Peri-operative Hemodynamics, Preoperative Sedation Scores Intra-operative Anesthetic Agent Requirement Data
present study, single dose of dexmedetomine was used provided appropriate anxiolysis and analgesia for
and no such beneficial effects were noticed. Further conducting invasive procedures and subsequent
studies can be conducted in renal transplant recipients epidural administration of these agents reduced
to demonstrate this effect of dexmedetomidine on the anaesthetic requirement and prolonged postoperative
grafted kidney. analgesia without compromising hemodynamics and
To conclude, dexmedetomidine-based respiratory parameters. Further dose finding studies
anaesthetic regimen versus fentanyl-based anaesthesia can be conducted in kidney transplant recipients.
Fig. 3
Postoperative Pain VAS scores
BALANCED ANESTHESIA FOR KIDNEY RECIPIENTS
557
References
1. James Baker, Spencer Yost, Claus Niemann U: Kidney renal transplantation. Anesth Analg; 1993, 76:362-65.
transplantation. In: Miller RD eds. Miller’s anaesthesia 7th ed. 20. Morita K, Seki T, Nonumura K: Changes in renal blood flow in
Elsevier Churchill Livingstone; 2010, 2161-66. response to sympathomimetics in the rat transplanted and denervated
2. Kazimirov VG, Pisariauk SN, Perlin DV: Advantages of epidural kidney. Int J Urol; 1999, 6:24-32.
anaesthesia in patients with end stage chronic renal failure. 21. Cronnelly R, Kremer PF, Beaupre P, et al: Haemodynamic
Anesteziol Reanimatol; 1995, 4:63-66. response to anaesthesia in patients with end stage renal disease.
3. Rockemann G, Seeling W, Pressler S, Steffen P, Georgiff M: Anesthesiology; 1983, 59:47-52.
Reduced postoperative analgesic demand after inhaled anaesthesia 22. Bhosale G, Shah V: Combined spinal-epidural anaesthesia for renal
in comparison to combined epidural-inhaled anaesthesia in patients transplantation. Transplant Proc; 2008, 40:1122-4.
undergoing abdominal surgery. Anesth Analg; 1997, 84:600-5. 23. Dauri M, Costa F, Servetti S, Sidirupoulou T, Fabbi E, Sabota AF:
4. Linke CL, Merin RG: A regional anaesthetic approach for renal Combined general and epidural anaesthesia with ropivacaine for
transplantation. AnesthAnalg; 1976, 55:69-73. renal transplantation. Minerva Anesthesiol; 2003, 69:873-84.
5. Akpek E, Kayhan Z, Kaya H, Candan S, Haberal M: Epiural 24. Morita K, Seki T, Nonumura K: Changes in renal blood flow in
anaesthesia for renal transplant. Transplant Proc; 1999, 31:3149-50. response to sympathomimetics in the rat transplanted and denervated
6. Hadimioglu N, Ertug Z, Bigat Z, Yilmaz M, Yegin A: A randomized kidney. Int J Urol; 1999, 6:24-32.
study comparing combined spinal epidural or general anaesthesia 25. Gabriels G, August C, Grisk O: Impact of renal transplantation on
for renal transplant. Transplant Proc; 2005, 37:2020-22. small vessel reactivity. Transplantation; 2003, 75:689-97.
7. Davies J, Silbert S, Mooney J, Dysart H, Meads C: Combined 26. Katarzyna R, Piotr K and Hanna M: The effect of dexmedetomidine
epidural and general anaesthesia versus general anaesthesia for sedation on brachial plexus block in patients with end-stage renal
abdominal aortic surgery. Anaesth Int Care; 1993, 21:790-94. disease. Eur J Anaesthesiol; 2009, 26:851-55.
27. Asano T, Dohi S, Shimonaka H, Lida H: Antinociception by epidural
8. McClure JH: Ropivacaine. Br J Anaesth; 1996, 76:300.
and systemic alpha 2-adrenoceptor agonists and their binding
9. Axelsson K, Gupta A: Local anaesthetic adjuvants: neuraxial versus
affinity in rat spinal cord and brain. Anesth Analg; 2000, 90:400-7.
peripheral nerve block. Curr Opin Anaesthesiol; 2009, 22:649-54.
28. Salgado PF, Sabbag AT, Silva PC: Synergistic effect between
10. Rawal N, Schott U, Dahlstrom B: Influence of naloxone infusion
dexmedetomidine and 0.75% ropivacaine in epidural anaesthesia.
on analgesia and respiratory depression following epidural
Rev Assoc Med Bras; 2008, 54:110-5.
morphine. Anesthesiology; 1986, 64:194-201.
29. Sukhminder JB, Vikramjit A, Jasbir K: Comparative evaluation of
11. Katarzyna R, Piotr K and Hanna M: The effect of dexmedetomidine
dexmedetomidine and fentanyl for epidural analgesia in lower limb
sedation on brachial plexus block in patients with end-stage renal
orthopedic surgeries. Saudi J Anaesth; 2011, 5:365-370.
disease. Eur J Anaesthesiol; 2009, 26:851-55.
30. Kasaba T, Kondero O, Yoshimuri Y, Watanbe Y, Takasaki M:
12. Asano T, Dohi S, Shimonaka H, Lida H: Antinociception by epidural
Haemodynamic effects of induction of general anaesthesia with
and systemic alpha 2-adrenoceptor agonists and their binding
propofol during epidural anaesthesia. Can J Anaesth; 1998, 11:1061-
affinity in rat spinal cord and brain. AnesthAnalg; 2000, 90:400-7.
5.
13. Elhakim M, Abdelhamid D, Abdelfattach H, Magdy H, Elsayed
31. Ngwenyama NE, Anderson J, Tobias JD: Effects of dexmedetomidine
A: Effect of epidural dexmedetomidine on intraoperative awareness
on propofol and remifentanil infusion rates during total intravenous
and postoperative pain after one lung ventilation. Acta Anaesthesiol
anesthesia for spinal surgery in adolescents. PaediatricAnaesth;
Scand; 2010, 18:703-9.
2008, 18:1190-5.
14. Chad B, Mary N, John M, Ralph L: Perineural administration 32. Carlier M, Squffle JP, Pirson Y, et al: Maximal hydration during
of dexmedetomidine in combination with bupivacaine enhances anaesthesia increases pulmonary arterial pressures and improves
sensory and motor blockade in sciatic nerve block without inducing early function in human renal transplant. Transplantation; 1982,
neurotoxicity in rat. Anesthesiology; 2008, 109:502-511. 34:201-7.
15. Al-Metwalli R, Mowafi H, Ismail H: Effect of intra-articular 33. Luciani J, Frantz P, Thibault P: Early anuria prevention in human
dexmedetomidine on postoperative analgesia after arthroscopic kidney transplantation. Advantage of fluid load under pulmonary
knee surgery. Br J Anaesth; 2008, 101:395-99. artery pressure monitoring during surgical period. Transplantation;
16. Chernik DA, Gillugs D, Laine H, et al: Validity and reliability of 1979, 28:308-12.
the observation and alterness/sedation score: study with intravenous 34. Kadieva VS, Friedman L, Margolius LP, Jackson SA, Morell DF:
midazolam. J clinpsychopharmacol; 1990, 10:244-51. The effects of dopamine on graft function in patients undergoing
17. Chapman CR, Case KL, Dubner R: Pain measurement overview. renal transplantation. AnesthAnalg; 1993, 76:362-65.
Pain; 1985, 22:1-31. 35. Akpek EA, Kayhan Z, Donmez A, Moray G and Arslan G: Early
18. Hadimioglu N, Ertug Z, Bigat Z, Yilmaz M, Yegin A: A randomized postoperative following renal transplantation surgery: Effect of
study comparing combined spinal epidural or general anaesthesia anaesthetic technique. J Anesth; 2002, 16:114-18.
for renal transplant. Transplant Proc; 2005, 37:2020-22. 36. Frumento RJ, Logginidou HG, Wahlander S: Dexmedetomidine
19. Kadieva VS, Friedman L, Margolius LP, Jackson SA, Morell DF: infusion is associated with enhanced renal function after thoracic
The effects of dopamine on graft function in patients undergoing surgery. J ClinAnesth; 2006, 18:422-6.