|Year : 2009 | Volume
| Issue : 4 | Page : 467-474
Comparison of Total Intravenous Anaesthesia Using Propofol with or without Sufentanil in Laparoscopic Cholecystectomies
M Subrahmanyam1, B SreeLakshmi2
1 Head of department, Department ofAnaesthesiology, Global Hospitals, Lakdi-ka-pool, Hyderabad-500004, India
2 DNB student, Department ofAnaesthesiology, Global Hospitals, Lakdi-ka-pool, Hyderabad-500004, India
|Date of Web Publication||3-Mar-2010|
20-450, Subhodayanagar, West Venkatapuram, Secunderabad-500015
Source of Support: None, Conflict of Interest: None
Sufentanil is an excellent adjuvant in total intravenous anaesthesia (TIVA). The present study evaluates effectiveness of differentconeentrations of Sufentanil mixed in propofol for TI VAin laparoscopic cholecystectomy. Sixty adult patients of ASA physical status I or II (randomly divided into 3 groups of twenty each) undergoing elective laparoscopic cholecystectomy were included in this randomised control study. At induction, patients in all groups received i.v. bolus of Sufentanil 1ìg kg-1 and continuous infusion of 100 ìg kg-1 min -1 . Anaesthesia was maintained with propofol infusion titrated in a range of 75 to 125ìg kg-1 min -1 . Groups S 1 and S2 received propofol with Sufentanil added at 1ìg ml -1 and 2 ìg ml -1 concentrations respectively, while group Preceived propofol without Sufentanil. Additional Sufentanil boluses (10 ìpg) were given to patients in all groups when there was an increase in the heart rate by more than 20 beats per minute or mean arterial pressure by more than 15% above baseline. Perioperative haemodynamic parameters, recovery times and postoperative analgesia were compared across the three groups of patients. Haemodynamie parameters (heart rate, systolic and diastolic blood pressures) were not significantly different across the three groups of patients in the perioperative period. Fewer Group S2 patients required additional Sufentanil boluses to maintain adequate depth of anaesthesia compared to other two groups. Group S2 patients had better post-operative analgesia (p=0.01) but prolonged recovery time (p=0A01) compared to the other two groups. Sufentanil mixed with propofol provides better haemodynamic stability in laparoscopic eholecystectomies, with lesser requirementfor additional Sufentanil boluses, and good postoperative analgesia.
Keywords: TIVA; Sufentanil; Propofol; Laparoscopic cholecystectomies
|How to cite this article:|
Subrahmanyam M, SreeLakshmi B. Comparison of Total Intravenous Anaesthesia Using Propofol with or without Sufentanil in Laparoscopic Cholecystectomies. Indian J Anaesth 2009;53:467-74
|How to cite this URL:|
Subrahmanyam M, SreeLakshmi B. Comparison of Total Intravenous Anaesthesia Using Propofol with or without Sufentanil in Laparoscopic Cholecystectomies. Indian J Anaesth [serial online] 2009 [cited 2020 May 29];53:467-74. Available from: http://www.ijaweb.org/text.asp?2009/53/4/467/60319
| Introduction|| |
Total intravenous anaesthesia (TIVA) is an evolved concept of general anaesthesia, which obviates the need for volatile anaesthetics. Propofol, a sedative-hypnotic agent with excellent recovery characteristics at the end of infusion and additional anti-emetic property, has become the drug of choice for TIVA. Newer synthetic opioids (fentanyl congeners) provide excellent analgesia and hence are popularadjuvants in TIVA. Sufentanil has been combined withpropofol in TI VA for various types of surgeries due to its advantages like synergistic action with propofol, rapid induction, less cardiovascular and respiratory depression, and rapid smooth recovery profile. ,, Additionally, early postoperative analgesia with intraoperative use of Sufentanil has been shown in previous studies to be better than that with fentanyl.  These properties can make Sufentanil an excellent adjuvant to propofo 1 in TIVA for upper abdominal lap aroscopic surgeries where the intraoperative haemodynamic fluctuations due to pneumoperitoneum and changes in patient position are better addressed. Sufentanil-propofol TIVAprovides clearheaded recovery of consciousness at emergence compared to inhalational anaesthesia and good postoperative analgesia, thus making it a useful combination for conducting these surgeries on a day care basis. ,, However,sufentanil's efficacy as an adjuvant to propofol in TIVAis yet to be addressed in laparoscopic cholecystectomies.
The present study seeks to assess the applicability of sufentanil, hamessmgthe advantages outlined m earlier studies, in TIVA for laparoscopic cholecystectomy. We hypothesized that continuous infusion of sufentanil and propofol will suppress the haemodynamic response to intubation and surgical stimulation; provide perioperative haemodynamic stability with rapid recovery and excellent postoperative analgesia in patients undergoing lap aroscopic cholecystectomies. This hypothesis was tested among three groups of patients undergoing laparoscopic cholecystectomy, referred henceforth as Group S1, Group S2, and Group P We used two different concentrations of sufentanil added to pmpofolto determine which combination had maximum benefits with least side effects. Groups S 1 and S2 received propofol with sufentanil added at 1 µg ml-1 and 2 µg m1 -1 , respectively. Group P received plain propofol without sufentanil. This group was intended to serve as control group.
| Methods|| |
This prospective randomized double blind study was conducted duringthe years 2006-07 after approval from the institutional ethics committee and written informed consent from the patients. Sixty adult patients (18 to 65 years) of ASA physical status I or II with Mallampati scores 1 and 2; scheduled to undergo elective laparoscopic cholecystectomy were included in the study. The study exclusion criteria were: Body weight more than 90 kg, history of hypertension on medications, history of coronary artery disease with or without percutaneous intervention on medications, history of long tern analgesic use, history of psychiatric disorders, patients with severe hepatic orrenal dysfunction (evident from previous medical records and present investigations) and patients in whom NSAIDS are contraindicated.
Patients who fulfilled the inclusion criteria during the pre-anaesthetic checkup were randomly assigned into three groups of twenty each with the help of computer-generatedtable ofrandom numbers. The operation theatre pharmacist assigned the concentration of sufentanil to be added to the prop ofol infusion for each group. Solutions ofpropofol containing different concentrations of sufentanil orno sufentanil were prepared m 50 ml syringes by the operation theatre pharmacist as per the randomization chart for each patient, immediately priorto induction. The intervention allocation was masked from the anaesthesiohgists conductingthe study, the patients, and the nurses monitoring the patients in the post-anaesthesia care unit and subsequently inthe ward.
Before start of anaesthesia, an intravenous access was secured on each patient with an 18 gauge intravenous catheter for fluid and dmg administration. Pie-induction measurementof heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and peripheral oxygen saturation (Sp 0 2 ) from the anaesthesia monitor was taken as the baseline measurement. Monitoring was continued throughout the period ofanaesthesia and included electrocardiography, pulse oximetry, non invasive arterial pressure and capnography. Patients were pre-oxygenated for 3 minutes with 100% 0 2 by facemask. Anaesthesia was induced with slow i.v. injection of sufentanil 1 µgkg -1 and continuous infusion ofpropofol 100 µg kg -1 mind. Loss of response to verbal commands was taken as the end point of induction following which intermediate-acting neuromuscular blocking agent; vecuronium 0.1 mg kg -1 was given. Trachea was incubated after 3 minutes ofmaskventilation and lungs were mechanically ventilated with O Z Air mixture and endtidal CO 2 concentration (EtCO 2 ) was maintained between 30-40 mm Hg. HR, SBP, DBP, and Sp0 2 were recorded 1, 3 and 5 minutes post-induction.
HR, SBP, DBP, Sp0 2 and EtCO 2 were monitored throughout the intraoperative period and recorded every 15 minutes in the observation sheet. All patients received propofol infusion titrated to the clinical situation in a range of 75 to 125 µgkg -l min -1. Hypotension, defined as systolic blood pressure below 80 mm Hg or mean arterial pressure below 60 mm Hg for more than 5 minutes, was treated by reducing propofol infusion by 10µg kg -1 min -1 , but within the range of 75 to 125 µg kg -1 min -1 . Additional intravenous fluids were given as deemed appropriate. Response was reassessed at 5 minute intervals and the above measures continued until stabilization of blood pressure. Hypertension, defined as systolicblood pressure above 150 mm Hg or mean arterial pressure above 95 mm Hg formore than 5 minutes, was treated by giving additional sufentanil (10 µg) boluses. Sufentanil boluses (10 µg) were also given to patients in all groups when there was an increase in the heart rate by more than 20 beats per minute or mean arterial pressure by more than 15% indicating lightening of anaesthesia. Response was reassessed at 5 minute intervals and the above measures repeated until stabilization. Neuromuscular paralysis was maintained with timely top up doses of vecuronium. Ten minutes before the anticipated end of surgery (at the start of skin suturing), the infusion was stopped. Total volume of propofol given by infusion for each patient was recorded. Total amount of sufentanil and the number of additional boluses of sufentanil given for each patient was recorded.
Residual neuromus cular blockade was reversed with neostigmine 2.5 mg and glycopyrrolate 0.5mg and trachea was extubated at the end of surgery following usual extubation criteria. The HR, SBP, DBP and Sp0 2 were recorded 1 and 5 minutes post-extubation. All patients received slow ix diclofenac 75mg added to 100m1 of nonnal saline at the end of surgery. Recovery time defined as time from stopping of prop ofol infus ion to complete return of consciousness as assessed by the ability of the patient to open eyes and tell his/her name on questioning, and to maintain adequate spontaneous breathing (respiratory rate above 12 breaths per minute), was recorded. Duration ofanaesthesia was recorded in minutes for allthe patients.
Patients were shifted to the post-anaesthesia care unit where HR, SBP, DBP, RR and Sp0 2 were recorded every 15 minutes for 2 hours. Allpatients were given supplemental oxygen with face mask. Postoperatively allpatients received oral diclofenac 50mgthree times daily. Postoperative pain was assessed for 24 hours by 10-cm visual analogue scale (VAS) on which 0 em represents no pain and 10 em represents worst imaginable pain.  In post-anaesthesia care unit or in ward, patients with VAS score above 3cm received rescue analgesic, tramadol 100mg intramuscularly. Number of patients requiringrescue analgesic and the time to first rescue analgesic requirement foreach patient, in first 24 hours p ostop eratively was recorded.
| Statistical analysis|| |
Statistical analyses were conducted on measured clinical data usingthe Statistics Tool Box of MATLAB software.  Power analysis was conducted aposterior and found to be more than 90% for comparing differences between the various parameters of interest.
The statistical means of continuous variables across the three groups (age in years, weight in kilograms and duration of anaesthesia m minutes)were analyzed by one-way analysis of variance (ANOVA). Chisquare (x 2 ) test was used to test differences between the groups for categorical variables (sex and ASAphysical status). The generalized linear modelrepeated measures procedure was used when repeated measurements were made on the same subject, as inthe case ofhaemodynamicmeasurements overthe perioperative period. Haemodynamic parameters (HR, SBP and DBP) were compared during the p erioperative period at different time intervals -pre-induction or baseline, post-induction, intraoperative, post-extubation and postoperative, using a Bonferroni adjusted generalized linear mo delrep eated measures procedure. The model includes age, sex, weight, duration of anaesthesia, volume ofpropofol and sufentanil, and baseline (pre-induction) haemodynamic variables as covariates, and adjusted forpotential interactions between covariates.
The total volume of pro pofol and total amount of sufentanil consumed by the three groups was compared using one-way ANOVA and Fisher tests. The recovery time from anaesthesiawas compared between the groups using a one-way ANOVA. Thetime to first rescue analgesia and the numberoftimes rescue analgesia was given were compared using ANOVA and a x 2test. Apvalue <0.05 was considered statistically significant.
| Results|| |
No patient dropped outafter enrolment and none of the potentially eligible patients met the exclusion criteria. Patients inthethree groups were comparable as regards age, sex, ASAphysical status, and duration ofanaesthesia[Table 1]. Weight was significantly different between the three groups (p=0.04). Themean weightwas lower in the Group S2 compared to S 1 and P.
Haemodynamic parameters' The three groups were similar in the baseline or pre-induction haemodynamic variables [Table 2]. There was no statistically significant difference across the three groups in systolic and diastolic blood pressures (SBP and DBP) in all the time periods studied. There was no statistically significant difference across the three groups in heartrate (HR)in allbut two time periods studied: postextubation and postoperative intervals [Table 2]. Howeverthis difference was notclinically significant.
Consumption ofpropofol and sufentanil Pa tients in Group S2 (mean volume 56.80 + 14.62 ml) required less propofol, though not statistically significant, compared with Group P (mean volume 65.50 + 15.68 ml) and Group S1 (mean volume 58.50 ±20.42 ml) [Table 3]. The amount of sufentanil at induction (µg) was highest for Group P compared to othertwo groups as the body weight was highest in this group. The total consumption of sufentanil was significantly high in Group S2 (184.15±38.30 µg) compared to Group S1 (136.3±27.13 µg) and Group P (81.75+17.79 µg), as expected from the study design.
Requirement of additional boluses of sufentanil Atotal of 13 patients in Group S2 did not require any additional sufentanilto maintain an adequate depth ofanaesthesia compared to 9patients inthe other two groups [Table 4]. The number of patients requiring additional sufentanil boluses intraoperativelyin Groups P, S 1 and S2, was 11, 11 and 7, respectively [Table 3]. However, the total amount of sufentanil given as boluses was not significantly different among those who required them [Table 3].
Recovery times Anaesthesiarecoverytime [Table 5] was longer for Group S2 (21 ± 9 minutes) cornpared to S 1(14 ± 6 minutes) and P(14± 5 minutes). The difference inthe meanrecovery times across all the groups has a statistical significance ofp J.001.
Rescue analgesic requirement Postoperatively, the number ofpatierits with VAS scores above 3 requiring rescue analgesia was significantly lowerin the S2 group (x 2p=0.01)[Table 5].Group S1 and S2 patients required firstrescue analgesic after 4hours into the postoperative period, while most of the Group P patients required rescue analgesic within 2hours post-extubation.
| Discussion|| |
The statistical analysis shows that patients in the three groups were comparable with regard to age, sex and ASA physical status; however, they differed with regard to body weight. The mean body weight was higher in group P compared to Groups S 1 and S2. This is taken into consideration in the statistical analysis of haemodynamic parameters by adjusting for potential interactions between covariates like age, sex, weight, duration of anaesthesia, volume of propofol and sufentanil, and baseline haemodynamic parameters.
No statistically significant difference was seen in the haemodynamic parameters across the three groups of patients in the perioperative period. Neither intubationstimulus, nor surgical incision, nor peritoneal insufflation with CO 2 had any influence onthe haemodynamic parameters in all groups. This may be attributed to the bolus of sufentanil (1 µg kg 1 ) given at induction. Our study confirms that synergistic pharmacodynamic interactions between propofol and sufentanil block responses to laparoscopic surgery. Similar observations were made in other surgical procedures , . Lysakowski et a1  studied the effects offentanyl and its congeners on loss of consciousness during propofolinduction of anaesthesia and concluded that analgesic concentrations of sufentanil enhance the anaesthetic effect of propofol and provide haemodynamic stability.
We observed that fewer Group S2 patients required additional boluses of sufentanil to maintain adequate depth of anaesthesia. The less errequirement of boluses is a consequence ofhaemo dynamic stability which in turn can be attributed to higher concentration of sufentanil (2 dug ml -1 ) used in Group S2. The bolus requirement was more frequent in the Groups P and Si, which could have contributed to the stability seen in haemodynamic parameters in these groups. 'Ihe mean decrease in the heart rate, systolic and diastolic blood pressures inperioperative period inthe study groups was within a clinically acceptable range. Monk et all reported similarfindings ofintraopemtive haemodynamic stability with sufentanil compared to other opioids. Elisabeth Hentgen et al  combined propofol and sufentanil in TIVA for thyroid surgery and observed that increasing target concentration of sufentanil provided better haemodynamic stability.
The sufentanil induction dose and propofol infusion rates used in our study were chosen based on dosage regimen suggested in earlier publications. , Previous studies showed that increasing concentrations of sufentanilreduce the volume ofpropofol consumed duringthe surgery. , Although ourstudy did not find a statistical difference in the total consumption of propofol, clinically, there was lesser consumption in Group S2patients [Table 3]. This marginal decrease could be due to lower body weight of the patients in this group or due to the higher concentration of sufentanil used. Alarger sample size might be ableto decisively answerthis question.
Recovery time was significantly prolonged (p=0.001) in Group S2 compared to the other two Groups. This delayed recovery in Group S2 patients, can be attributed to requirement of more than one sufentanil bolus in 15% of patients in addition to the higher concentration of sufentanil (2 µg ml -1 ). No significant difference was observed in Group S 1 where 50% patients required one sufentanil bolus in addition to 1.tg ml -1 concentration of sufentanil, compared to Group P where about 20% patients needed multiple boluses [Table 4]. Similar conclusions were drawn by Elisabeth Hentgen et al  in a previous study that combined increasing target concentrations of sufentanil with propofol in TIVA for thyroid surgery. Ourfindings in lap aroscopic cholecystectomy confirm the conclusions reached by earlierstudies of sufentanil in othersurgical procedures. It is important to note that the observed 7-minute prolongation ofrecovery time was clinically insignificant in our setting where the patients undergoing laparoscopic cholecystectomy get discharged from the hospital onthe frrstpostoperative day.
Postoperative analgesia was better in Group S2 (x2 p=0.01)compared with the othertwo groups. Patients in Group S2 had excellent 24-hour postoperative analgesia (VAS score less than 3) with least requirement ofrescue analgesia. Group S 1 patients had good early postoperative analgesia with greater rescue analgesic requirement in the laterpostoperative period (more than 4 hours postoperatively). In patients who received plain prop ofo 1 (Group P) there was a greater requirement ofintraoperative sufentanil boluses and highest rescue analgesic requirement in the early postoperative period compared to the othertwo groups. Derrode et al  compared effects of target-controlled infusions of sufentanil and remifentanil administered along with propofol on recovery and postoperative analgesia after maj or abdominal surgery. They observed that quality of postoperative analgesia depends on the opioid infused during surgery and concluded that intraoperative use of sufentanil was very effective in providing excellent 24-hour postoperative analgesia. Our study also suggests that sufentanilat a concentration of 2 ìg ml -1 provides better quality ofintraoperative and postoperative analgesia in lap aroscopic cholecystectomy.
In summary, sufentanil mixed in propofol for TIVA in laparoscopic cholecystectomy gives adequate depth of anaesthesia, stable haemodynamics, good postoperative analgesia, and a slightly prolonged recovery time.
Sufentanil is an effective adjuvant in TIVA for laparoscopic cholecystectomy. This study concludes that both concentrations of sufentanil achieve the goals of stable haemodynamics without a clinically significant prolongation of recovety time. However, 2ìg ml -1 concentration of sufentanil added to propofol provided greater perioperative haemodynamic stability with lesser requirement for additional boluses and excellent postoperative analgesia. The influence of sufentanil on recovery times needs further clinical trials with larger sample sizes.
| References|| |
|1.||Monk JP, Beresford R, Ward A. Sufentanil. Areview of its pharmacological properties and therapeutic use. Drugs 1988; 36: 286-313 |
|2.||Vuyk J, Mertens IVLT, Olofsen E, et al. Propofol anesthesia and rational opioid selection: determination of optimal EC 50 -EC 95 Propofol opioid concentrations that assure adequate anesthesia and a rapid return of consciousness. Anesthesiology 1997; 87: 1549-1562 |
|3.||Ahonen J, OlkkolaK. T Hynynen M, Seppala T Tkavalko H,RemmerieB, SalmenperaM Comparisonofalfentanyl, fentanyl and Sufentanil for total intravenous anaestheia with Propofol in patients undergoing coronary artery bypass surgery. Br J Anaesth 2000; 85: 533-540. |
|4.||Apfel CC, Kranke P, Katz MH, et al. Volatile anaesthetics may be the main cause of early but not delayed postoperative vomiting: a randomized controlled trial of factorial design. Br JAnaesth2002; 88: 659-668. |
|5.||Nightingale JJ, Lewis I H. Recovery from day-case anaesthesia: Comparison of Total LV Anaesthesia using Propofol with an inhalational technique. Br J Anaesth 1992;68: 35&359. |
|6.||Derrode N, Lebrun F, Levron JC, Chauvin IA, Debaene B. Influence of peroperative opioid on postoperative pain after maj or abdominal surgery: Sufentanil TCI versusremifentanil TCI. Br JAnaesth 2003; 91: 842 -849. |
|7.||W. B. Saunders Company; 2003 MATLAB, Version 7.0 (Release 14), MATH WORKS inc, 2004. |
|8.||Vuyk J, Lim T, Engbers FHM, Burm AGL, Vletter AA, Bovil LO. The pharmacodynamic interactionofPropofol and alfentanil during lower abdominal suleryin wornen. Anesthesiology 1995;83: 8-22. |
|9.||Vyuk J. Clinical interpretation of pharmacokinetic and pharmacodynamic Propofol-opioid interactions. Acta Anaesthesiol Belg 2001:52:445-451. |
|10.||Lysakowski C, Dumont L, Pellegrini M Clergue F, Tassonyi E. Effects of fentanyl, alfentanil, remifentanil and Sufentanil on loss of consciousness and bispectral index during Propofol induction of anaesthesia. Br J Anaesth 2001; 86 :523-527. |
|11.||Elisabeth Hentgen, Malik Houfani, Valerie Billard, Florent Capron, Jean-Mare Ropars, Jean Paul Travagli. Propofol-Sufentanil Anesthesia for Thyroid Surgery: Optimal Concentrations for Haemodynamic and Electroencephalogram Stability, and Recovery Features. AnesthAnalg 2002; 95: 597-605. |
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]