A Prospective, Randomized, Single-Blind, Comparative Study of Dexmedetomidine and Propofol Infusion for Intraoperative Hemodynamics and Recovery Characteristics in Laparoscopic Surgeries.

BACKGROUND: Creation of pneumoperitoneum in laparoscopic surgeries with carbondioxide to intra-abdominal pressures higher than 10 mmHg induces significant alterations of hemodynamics. To counteract, propofol or dexmedetomidine was compared and postoperative recovery assessed. AIMS: The aim of this study was to compare the efficacy of standard dose of propofol versus low-dose dexmedetomidine as infusions to limit hemodynamic instability with pneumoperitoneum and facilitate recovery. SETTINGS AND
DESIGN: This was a prospective, randomized, single-blind, comparative study.
MATERIALS AND METHODS: Seventy patients between 18 and 60 years belonging to the American Society of Anesthesiologists Physical Status Class 1 and 2 scheduled for laparoscopic surgeries were randomly divided - Group D: To receive dexmedetomidine 1 μg/kg over 10 min before and 0.2 μg/kg/h infusion after intubation till the end of pneumoperitoneum and Group P: To receive propofol 100 μg/kg/min after intubation till the end of pneumoperitoneum. Variables such as heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were recorded at baseline, preinduction, after loading dose of dexmedetomidine, postinduction, postintubation, at pneumoperitoneum, every 15 min till the end of surgery, at extubation, and postoperatively for 2 h monitored with Ramsay Sedation Scale and modified Aldrete's score.
RESULTS: Hemodynamic stability was better maintained in Group D than Group P with significant attenuation of hemodynamic stress response to pneumoperitoneum in terms of HR (3% decrease vs. 18% increase), SBP (5% decrease vs. 12% increase), DBP (2%increase vs. 16% increase), and MAP (4% decrease vs. 7% increase). Postoperatively, significant sedation was noted till 90 min in Group D and recovery was better in Group P.
CONCLUSION: With doses of test drug infusion used, there is better attenuation of hemodynamic stress response to pneumoperitoneum with dexmedetomidine and faster recovery with propofol. Copyright:

INTRODUCTION

Laparoscopy is an operation performed in the abdomen or pelvis through small incisions with the aid of a camera. Surgery involving laparoscope is also called minimally invasive surgery because operations are performed using multiple small incisions (0.5–1.5 cm) in contrast to traditional methods which use large incisions.

The laparoscopic approach has been gaining popularity for several reasons [Figure 1].

Figure 1

Advantages of laparoscopic surgical approach

The higher cost of the procedure may be outweighed by benefits including lack of or shorter hospitalization and earlier return to work.

The procedure of laparoscopy essentially involves creating an artificial pneumoperitoneum, usually using carbon dioxide (CO2) gas. Using CO2 is associated with various pathophysiological changes, especially involving cardiovascular and respiratory systems [Figure 2].

Figure 2

Pathophysiological changes involving cardiovascular and respiratory systems

Also, laparoscopic cholecystectomy is performed in the reverse trendelenburg position which leads to diminished venous return and hence further reduces cardiac output.[1]

These changes are usually well tolerated by healthy adults but can be detrimental in the elderly and in patients with cardiorespiratory compromise.

Figure 3

To overcome these changes, various interventions [Figure 3] have been tried

Propofol is one of the standard drugs used for hemodynamic stability during pneumoperitoneum. Propofol[2] is a nonopioid, nonbarbiturate, sedative hypnotic agent with rapid onset and short duration of action. Total intravenous (IV) anesthesia with propofol was shown to be more effective in inhibiting the neuroendocrine stress response compared with volatile anesthesia.[3]

Dexmedetomidine is a selective α2-adrenergic receptor agonist which is known to produce sedation and analgesia,[4] and also has sympatholytic, anesthetic sparing, and hemodynamic stabilizing properties without significant respiratory depression.[5] Dexmedetomidine has been tried in varying dose regimens for blunting hemodynamic response to pneumoperitoneum. However, higher doses are associated with side effects.

There are very few studies comparing the effect of lower dose of dexmedetomidine with propofol to maintain hemodynamic stability during pneumoperitoneum.[678]

The present study was designed to compare the effect of low dose of dexmedetomidine over a standard dose of propofol infusion.

MATERIALS AND METHODS

This was a prospective, randomized, comparative, single-blind study:

Hypothesis

We hypothesized that the infusion of dexmedetomidine might produce lesser increase in mean arterial pressure (MAP) during laparoscopy compared to the infusion of propofol.

Sample size

To detect a minimum of 5% difference in MAP between the two groups, a minimum of 33 patients are required in each group assuming beta error at 20% and alpha error at 5%. Hence, we included 35 patients in each group for better validation of results.

Ethical clearance was obtained from the Institutional Ethical Committee dated November 16, 2015.

The study was conducted on 70 inpatients undergoing laparoscopic surgeries between November 2015 and May 2017.

Inclusion criteria

Patients aged 18–60 years, patients scheduled for laparascopic surgeries such as laparascopic cholecystectomy, and patients belonged to the American Society of Anesthesiologists (ASA) Physical Status Classes I and II were included in the study.

Exclusion criteria

Patients refusing to participate in the study; patients with liver, renal, and cardiac disorder; and patients with any degree of heart block, preexisting hypertension, on beta blockers, and allergies to the drugs used were excluded from the study.

Patients were randomly allocated using random allocation number table to one of the two groups: Group D and Group P (n = 35 each).

Group D – Received dexmedetomidine infusion as a loading dose of 1 μg/kg over 10 min before and 0.2 μg/kg/h after intubation.

Group P – Received propofol infusion of 100 μg/kg/min after intubation.

Preanesthetic evaluation was done on previous day, and protocol explained to patients in brief.

Anesthesia workstation was checked. Appropriate sized endotracheal tubes, working laryngoscope with blade 3 and 4, stylet, and working suction apparatus were kept ready before procedure. After shifting the patient to operating room, two IV lines were secured: one for IV fluids and drugs and another for administering of the test drug. Dexmedetomidine and propofol were prepared in infusion syringes at 10 μg/ml and 10 mg/ml, respectively.

Baseline monitors such as electrocardiogram, pulse oximetry, and noninvasive blood pressure (BP) were attached. End-tidal CO2 (ET CO2) monitor was connected. Baseline values of heart rate (HR), saturation (SpO2), BP, and ETCO2 were noted.

Patients of both groups were premedicated with glycopyrrolate 4 μg/kg, midazolam 0.03 mg/kg, and fentanyl 1.5 μg/kg IV. Group D received a loading dose of dexmedetomidine 1 μg/kg over 10 min. Both groups were induced with injection sodium thiopental 5 mg/kg and injection succinylcholine 2 mg/kg. Intubation was achieved with appropriate-sized cuffed endotracheal tube and secured with plasters after confirming bilateral air entry. Thereafter, dexmedetomidine infusion was started at 0.2 μg/kg/h in Group D and injection propofol infusion at 100 μg/kg/h in Group P.

Patients were maintained with O2:N2O mixture of 40:60 connected to closed circuit and inhalational agent sevoflurane 0.8% to maintain depth of anesthesia with entropy values between 40 and 60. Muscle relaxation was maintained with injection atracurium 0.1 mg/kg. Test drug infusion was discontinued on deflation of pneumoperitoneum.

Patients were reversed with injection neostigmine 0.05 mg/kg and injection glycopyrolate 8 μg/kg IV and were extubated after adequate return of muscle power and protective reflexes.

Intraoperative monitoring was documented during the preinduction, after the loading dose of dexmedetomidine, at the induction of anesthesia, during intubation, and at the initiation of pneumoperitoneum, and then every 15 min till the end of surgery and continued during extubation and postoperatively for 2 h.

Any side effects such as hypotension (MAP <30% baseline, treated with injection mephenteramine 6 mg IV), bradycardia (HR <60 bpm, treated with injection atropine 0.01–0.02 mg/kg IV), respiratory depression, postoperative nausea, and vomiting were noted and treated appropriately. Patients were observed in the recovery room for 2 h before shifting to the ward. Recovery characteristics were assessed using modified Aldrete's score and Ramsay Sedation Scale.

Statistical analysis

Continuous variables were expressed as mean ± standard deviation.

Student's t-test was used (independent t-test for intergroup variation and paired t-test for intragroup variation).

Data were analyzed using IBM SPSS version 20 (IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp) software P ≤ 0.05 was considered significant.

RESULTS

The two groups were comparable regarding age, sex, weight, ASA Physical Status, and duration of anesthesia (P > 0.05) [Table 1].

Table 1

Demographic details

	Group D (mean±SD)	Group P (mean±SD)
Age ( years)	40.8±6.28	40.65±6.5
Sex
Male	19	21
Female	16	14
Weight	53.91±7.07	51.06±5.09
Duration of surgery	59.42±7.4	56.33±9.2
ASA physical class
Class I	88.6%	85.7%
Class II	11.4%	14.3%

SD=Standard deviation

Preinduction HR, systolic BP (SBP), diastolic BP (DBP), and mean BP (MAP respectively) were comparable between the two groups (P > 0.05).

HR in patients belonging to Group D was lower than in patients in Group P at all time periods, and it was found to be statistically and clinically significant from 5 min of initiation of dexmedetomidine infusion. The mean HR in the Group D showed a 5% fall as compared to 9% rise in the Group P from the baseline [Figure 4].

Figure 4

Comparison of heart rate

SBP was lower in patients in Group D during the period of study drug administration and throughout the period of pneumoperitoneum which was statistically and clinically significant [Figure 5].

Figure 5

Comparison of systolic blood pressure

The DBP also showed similar lower values in Group D compared to Group P at all-time intervals, especially after the initiation of study drug infusion, throughout the period of pneumoperitoneum; as shown by a P < 0.001 (Student's t-test) [Figure 6].

Figure 6

Comparison of diastolic blood pressure

The comparison of MAP by Student's t-test showed a statistically significant difference between both the groups. Patients in the Group D had a lower MAP at all time periods which was more pronounced and statistically significant in reducing pressor response to pneumoperitoneum [Figure 7].

Figure 7

Comparison of mean arterial pressure

Patients in Group D demonstrated a persistent higher sedation scores for up to 90 min postoperatively than Group P [Figure 8].

Figure 8

Comparison of Ramsay sedation score

Patients in Group D had delayed recovery scores for up to 30 min postoperatively than Group P [Figure 9].

Figure 9

Comparison of modified Aldrete score

DISCUSSION

The pneumoperitoneum and the patient positions required for laparoscopy induce pathophysiologic changes that complicate anesthetic management. Peritoneal insufflation to intra-abdominal pressures (IAPs) higher than 10 mmHg induces significant alterations of hemodynamics.[910] These disturbances are characterized by decreases in cardiac output, increased arterial pressures, and elevation of systemic and pulmonary vascular resistances. HRs remain unchanged or increased only slightly. The decrease in cardiac output is proportional to the increase in IAP whether the patient was placed in the head-down or head-up position.[10]

The mechanism of the decrease of cardiac output is multifactorial [Figure 10].

Figure 10

Mechanisms of decrease in cardiac output

The increase in systemic vascular resistance is affected by patient position. The Trendelenburg position attenuates this increase; the head-up position aggravates it.

Use of α2-adrenergic agonists such as clonidine, or dexmedetomidine, and of β-blocking agents significantly reduces hemodynamic changes and anesthetic requirements. Use of high doses of remifentanil almost completely prevents the hemodynamic change. Propofol boluses[11] have been used to control hemodynamic changes that occur during laparoscopy.

Dexmedetomidine, an imidazoline derivative, is a selective α2-adrenergic agonist with sedative, anxiolytic, analgesic, sympatholytic, and antihypertensive effects. It produces a fall in the HR and BP associated with decreased systemic vascular resistance by activating presynaptic α2-adrenergic receptors. Various studies report using dexmedetomidine infusion rates ranging from 0.1 to 10 μg/kg/h. Higher infusion rates had higher incidence of adverse events such as hypotension and bradycardia.

Propofol is a nonopioid, nonbarbiturate, sedative hypnotic agent with rapid onset and short duration of action. Propofol consists of a phenol ring substituted with two isopropyl groups acts by facilitation of inhibitory neurotransmission mediated by GABAA receptor binding causing decrease in arterial BP due to a drop in systemic vascular resistance (inhibition of sympathetic vasoconstrictor activity), preload, and cardiac contractility. Rarely, a marked drop in preload may lead to a vagally mediated reflex bradycardia.

Our study included 70 patients of ASA 1 and 2 physical status who were scheduled for laparoscopic cholecystectomy. Although initially intended to include patients undergoing laparoscopic appendicectomy due to lack of cases during my study period, this study included only patients undergoing laparoscopic cholecystectomy.

Ishizaki et al.[12] tried to evaluate the safe IAP during laparoscopic surgery. They observed a significant fall in cardiac output at 16 mmHg of IAP.

Cunningham et al.[13] and Dorsay et al.[11] assessed the ejection fraction (EF) of left ventricle by transoesophageal echocardiography during pneumoperitoneum. No significant change in ejection fraction was reported up to 15 mm Hg of intra-abdominal pressure. Considering all these facts intra abdominal pressure was kept below 12 mm Hg.

In our study, ETCO2 level was maintained between 30 and 40 mmHg and IAP below 12 mmHg.

Bhattacharjee et al.[14] in 2010 studied the effects of dexmedetomidine low-dose infusion of 0.2 μg/kg/h in patients undergoing laparoscopic cholecystectomy and observed that HRin dexmedetomidine group was significantly less after intubation and throughout the period of pneumoperitonium which concurs with our study. In our study, there is a statistically significant increase in HR in the propofol group compared to dexmedetomidine group after intubation. From insufflation to the end of pneumoperitoneum, during reversal and extubation, HRs were higher in the propofol group compared to dexmedetomindine group, demonstrating similar results with better control of HR with low-dose infusion of dexmedetomidine.

The control of the SBP was significantly better in dexmedetomidine group compared to propofol group. Statistically significant difference was found from 5 min of beginning dexmedetomidine infusion, during intubation, throughout the intraoperative period during pneumoperitoneum, and during extubation. Similar differences were noticed in DBP of both the groups and were found to be clinically and statistically significant from 10 min following initiation dexmedetomodine infusion till the end of surgery and during extubation. Study observations done by Vandana et al.[7] using dexmedetomidine concur with our study. Mean SBP and DBP after initial drop with loading dose of dexemedetomidine was maintained without much fluctuation throughout pneumoperitoneum, demonstrating good control over the vasopressor response during laryngoscopy, with minimal or no change in BP with pneumoperitoneum.

MAP was consistently maintained at a lower level with dexmedetomidine infusion suppressing pressor response to intubation, throughout pneumoperitoneum, and during extubation, and this was evident statistically. Mean Arterial Pressure (MAP) was consistently maintained at a lower level with dexmedetomidine infusion suppressing pressor response to intubation, throughout pneumoperitoneum and during extubation and this was evident statistically. Our observations concurs with the observations done by Vandana S et al.[7] in their study comparing effect of dexmedetomidine and propofol as infusions during laparoscopic surgery, concluded that dexmedetomidine attenuates hemodynamic response to laryngoscopy and pneumoperitoneum with adequate depth of anesthesia better than propofol.

We monitored recovery by modified Aldrete's score and Ramsay Sedation Scale. It was observed that patients in propofol group showed a faster recovery compared to dexmedetomidine group, and this was evident with the statistics with P < 0.05 up to 90 min by Ramsay Sedation Scale and up to 30 min by modified Aldrete's score. Our findings are supported by the study done by Arain and Ebert.[8] in 2002 who compared dexmedetomidine versus propofol for intraoperative sedation. Our study also shows delayed recovery and discharge from postoperative care unit due to higher sedation scores in Group D in spite of using lower doses of dexmedetomidine.

The limitations of our study include the following: first, our study is a single-blind study; due to practical logistics, double-blinding was not feasible. Second, the study group composed of ASA I and II patients. Further studies will be required to assess whether the same can be applied in other patient populations. Third, anesthetic sparing properties of dexmedetomidine such as consumption of inhalational anesthetics and requirement of opioids/analgesics were not monitored.

CONCLUSION

Our study demonstrates that either of the test drug infusions can be used in patients undergoing laparoscopic surgery to achieve stable hemodynamics and concludes with the observation of Dexmedetomidine infusion (@1mg.kg-1 loading dose followed by 0.2mg.kg-1.h-1) producing better stability in hemodynamics during pneumoperitoneum compared to propofol infusion (100mg.kg-1.min-1) and propofol infusion produces faster recovery compared to sedative property of dexmedetomidine infusion necessitating postoperative monitoring.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.