|Year : 2018 | Volume
| Issue : 2 | Page : 555-560
A comparative study evaluating effects of intravenous sedation by dexmedetomidine and propofol on patient hemodynamics and postoperative outcomes in cardiac surgery
Tufail Ahmad Sheikh1, Bashir Ahmad Dar2, Nihida Akhter3, Nadeem Ahmad4
1 Department of Anesthesiology and Critical Care, Government Medical College, Srinagar, Jammu and Kashmir, India
2 Department of Anesthesiology and Critical Care, Sheri Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
3 Department of Gynecology and Obstetrics, Lal Ded Hospital, Srinagar, Jammu and Kashmir, India
4 Department of Gastroenterology, Sheri Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
|Date of Web Publication||14-Jun-2018|
Dr. Tufail Ahmad Sheikh
Department of Anesthesiology and Critical Care, Government Medical College, Srinagar, Jammu and Kashmir
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: The use of intravenous sedation during cardiac surgery to reduce awareness has been practised routinely during past few years and the two most commonly used drugs include propofol and dexmedetomidine, but their effects on hemodynamics and postoperative outcomes in cardiac surgery is continually being evaluated. Aims: The aim of this study was to compare the effects of anesthesia by dexmedetomidine and propofol on the hemodynamic variables and postoperative outcomes in patients who were planned for elective cardiac surgery. Settings: Cardiac operating room of a tertiary care hospital. Design: A prospective, randomized controlled, double-blind clinical trial. Materials and Methods: Sixty patients were randomized to receive either a continuous infusion of propofol (0.25–1 mg/kg/h) or dexmedetomidine bolus of 1 μg/kg over 10 min followed by infusion (0.2–0.6 μg/kg/h) after induction of anesthesia. The anesthesia technique and physiological monitoring including bispectral index monitoring were similar among both the groups. Hemodynamic variables (mean heart rate [HR], mean arterial pressure [MAP]) were noted at predefined time intervals, intraoperative vasopressor or inotrope requirements and postoperative outcomes including postoperative ventilation time and length of stay in the Intensive Care Unit (ICU) were also recorded. Statistical Analysis: Statistics was done using SPSS V 20 (IBM, NY) using Student's t-test, analysis of variance, and Mann–Whitney U-test, and a P < 0.05 was considered to indicate a significant difference. Results and Conclusions: HR and MAP were significantly less in dexmedetomidine group compared to propofol group (P < 0.05). Both the groups had a similar requirement of vasopressors and inotropes. The duration of postoperative ventilation and length of stay in the ICU were significantly shorter in the dexmedetomidine group (P < 0.05). The risk of delirium was significantly less in dexmedetomidine group (P < 0.05). From our study we concluded, that the perioperative infusion of dexmedetomidine produces better hemodynamic stability, reduces the risk of postoperative delirium, and leads to shorter ICU stay.
Keywords: Cardiac anesthesia, cardiopulmonary bypass, delirium, hemodynamic, Intensive Care Unit, sedation
|How to cite this article:|
Sheikh TA, Dar BA, Akhter N, Ahmad N. A comparative study evaluating effects of intravenous sedation by dexmedetomidine and propofol on patient hemodynamics and postoperative outcomes in cardiac surgery. Anesth Essays Res 2018;12:555-60
|How to cite this URL:|
Sheikh TA, Dar BA, Akhter N, Ahmad N. A comparative study evaluating effects of intravenous sedation by dexmedetomidine and propofol on patient hemodynamics and postoperative outcomes in cardiac surgery. Anesth Essays Res [serial online] 2018 [cited 2020 May 27];12:555-60. Available from: http://www.aeronline.org/text.asp?2018/12/2/555/234425
| Introduction|| |
The use of dexmedetomidine in cardiac anesthesia is on the rise as several recently published studies have demonstrated cardiovascular stability in cardiac surgery due to its use. The properties of being a good analgesic, sedative, anxiolytic, and sympatholytic agent made it a useful agent to be used with routine anesthetic intravenous induction drugs. It attenuates the hypertensive response to endotracheal intubation in cardiac surgery patients  and produces stable hemodynamics at the time of incision and sternotomy, considerably reducing the requirement of other intravenous anesthetic agents. It was once believed that perioperative use of dexmedetomidine provides cardiac protection; however, this was not supported by a study conducted by Tosun et al.
Very few meta-analyses are available in the literature addressing the use of dexmedetomidine in cardiac surgery patients. One such study demonstrated a reduction in the incidence of delirium, ventricular tachycardia and duration of mechanical ventilation in cardiac surgery patients by the use of dexmedetomidine. Another meta-analysis  evaluated the outcome of cardiac surgery patients with the use of dexmedetomidine. The authors showed that dexmedetomidine use reduces the risk of atrial fibrillation, ventricular tachycardia, and postoperative delirium. It caused dexmedetomidine. This meta-analysis revealed that the perioperative use of dexmedetomidine in patients undergoing cardiac surgery can reduce the risk of postoperative ventricular tachycardia and delirium, but may increase the risk of bradycardia. The estimates showed a decreased risk of atrial fibrillation, shorter length of ICU stay and hospitalization, and increased risk of hypotension with dexmedetomidine.
Propofol is an intravenous anesthetic agent that is used for induction and maintenance of anesthesia. The use of propofol for induction of anesthesia in patients undergoing cardiac surgery is well described.,, In these studies, doses of propofol of 1.0–2.5 mg/kg were associated with significant hypotension.
This study aimed to compare hemodynamic responses of dexmedetomidine and propofol infusions in cardiac surgery used to provide adequate levels of sedation throughout the procedure. In addition, this study examined the comparative potential impact of intraoperatively administered dexmedetomidine on major end-points such as postoperative ventilation, Intensive Care Unit (ICU) stay, myocardial ischemia, stroke, coma, heart block, delirium, and acute renal failure during the postoperative period for patients undergoing cardiac surgery.
| Materials and Methods|| |
This prospective, randomized study was conducted in a tertiary care hospital for a period of 2 years from July 2014 to June 2016. After receiving the approval of the Institutional Ethical Committee, 60 patients aged 15–60 years with the American Society of Anesthesiologists physical Status I–III, planned for elective open heart surgery were included in this study. Proper informed consent was taken from all patients included in the study. Exclusion criteria were-age more than 60 years, patients having neurological/psychological disorders, severe systemic disorders (renal/hepatic dysfunction and severe respiratory disorder), history suggestive of allergy to the study drugs, left ventricular ejection fraction < 40%, and patients with infusions of catecholamine's or vasodilators. The study was designed in a prospective, randomized double-blind manner. Patients were randomly separated into two groups–dexmedetomidine (n = 30) and propofol (n = 30), using computer-generated random numbers placed in sealed envelopes. Patients were premedicated with intramuscular midazolam 0.05 mg/kg given 30 min before the surgery. After arrival in the operating room, intravenous access was obtained with an 18G peripheral venous cannula. Routine physiological monitoring, including electrocardiography (ECG), pulse oximetry, noninvasive blood pressure, temperature, neuromuscular and urine output monitoring, was initiated. In all patients, baseline systolic arterial pressure, diastolic arterial pressure, and baseline heart rate (HR) values were recorded. All the hemodynamic measurements were made by yet another anesthesiologist who was blinded to the groups. Depth of anesthesia was evaluated using bispectral index (BIS) monitor. BIS was obtained using disposable sensors (Aspect Medical Systems, Inc., Norwood, MA, USA). After wiping patients skin with alcohol and drying, BIS sensors were placed diagonally on the forehead as follows: one at the center of forehead approximately 2 inches above the bridge of nose; second, one directly above forehead, and third, one on temple between the corner of the eye and hairline. BIS displayed on the monitor (Mindray WATO EX-65, China) was recorded. Patients were induced with propofol (1–2.5 mg/kg), morphine (0.1–0.2 mg/kg), and isoflurane (minimum alveolar concentration 1.2). After the loss of eyelid reflex, vecuronium (0.1–0.2 mg/kg) was administered intravenously to facilitate tracheal intubation. The dexmedetomidine group received a bolus dose of dexmedetomidine (1 μg/kg diluted in 100 ml of normal saline over 10 min), followed by infusion (0.2–0.6 μg/kg/h). The propofol group received a propofol infusion at the rate of 0.25–1 mg/kg/h. Blinding to propofol was achieved by shielding the infusion syringe, tubings, and intravenous site from the view of everyone. Target BIS was kept at 50 ± 10. The lungs were ventilated using intermittent positive pressure ventilation with tidal volume of 6–8 mL/kg and fraction of inspired oxygen (FIO2) 100%. Ventilation was controlled to end-tidal carbon dioxide of 35–45 mmHg by adjusting tidal volume and respiratory rate. Invasive arterial blood pressure and central venous pressure monitoring were done. Anesthesia was maintained with isoflurane and 0.05 mg/kg morphine administered before skin incision and sternotomy, at start and toward the end of cardiopulmonary bypass (CPB). Muscle relaxation was maintained with vecuronium bromide (0.01–0.02 mg/kg). Hypotension (systolic blood pressure [SBP] <90 mmHg) with a HR <50 bpm was managed by 5 mg ephedrine administered intravenously. Hypotension (SBP <90 mmHg) with a HR of ≥50 bpm, was managed with 50 μg phenylephrine administered intravenously. In the case of bradycardia (HR <40 bpm), 0.6 mg atropine was administrated. Hypertension (SBP >160 mmHg) was treated with 50 μg nitroglycerine boluses, and tachycardia (HR >100 bpm) was treated by 5 mg esmolol. Anticoagulation was maintained with 350 U/kg of unfractionated heparin for CPB. The kaolin-activated coagulation time was measured every 30 min, and if the activated coagulation time was <480 s, additional heparin (100 U/kg) was administered during CPB. After the termination of CPB, 1 mg of protamine sulfate per 100 U of heparin was given to all the patients. Roller pumps and membrane oxygenators (MAQUET HL20 heart-lung machine, Germany) were used in the CPB circuit. Among both the groups, the protocol for CPB included moderate hypothermia (temperatures between 28°C and 30°C), flows maintained between 2.0 and 2.4 L/min/m 2, and mean arterial pressure (MAP) of 50–80 mmHg. While patients were on full CPB flows, lungs were not ventilated. Hypertension was treated by decreasing pump flow or by administration of nitroglycerine. Hypotension was corrected using increased pump flow or phenylephrine, as clinically indicated. Myocardial protection was achieved with cold blood cardioplegia solution. Patients were actively warmed to 37°C. Infusions of propofol or dexmedetomidine were continued during CPB, and isoflurane was used before and after CPB, as at our institute it was not feasible to add isoflurane to the CPB circuit. After skin closure, study drug infusions were stopped and the patients were shifted to cardiothoracic ICU (CICU) for elective mechanical ventilation.
HR and MAP at the following predetermined times were recorded and compared between the two groups – 15, 30, 45, and 60 min, respectively, after induction; 5, 30, 60, and 90 min, respectively, after the start of CPB; 5, 30, and 60 min after CPB, and at the end of surgery. Intraoperative requirement of vasopressors and inotropes was also noted down in both groups.
On arrival at the CICU, a standardized protocol for postoperative care was implemented for all patients. Ventilation was achieved by the use of pressure regulated volume control with tidal volume of 8–10 mL/kg, rate 10–15/min, positive end-expiratory pressure 5–10 cm H2O, and FIO20.6–1.0. Weaning criteria were hemodynamic stability (no use or decreasing use of cardioactive drugs), absence of significant bleeding (<100 mL/h), no significant arrhythmias, adequate urine output (>1 mL/kg/h), and oxygen saturation >95% with FIO2<0.5; neurologically, the patient needed to be sufficiently awake to respond to commands. Postoperative outcomes included length of mechanical ventilation and duration of ICU stay, any complications like myocardial infarction, stroke, coma, heart block, renal failure and delirium. The following definitions were used. Postoperative stroke was defined as any abrupt onset confirmed neurological deficit caused by a disturbance in cerebral blood supply that did not resolve within 24 h. Coma was defined as a new postoperative coma that persisted for at least 24 h secondary to anoxic/ischemic or metabolic encephalopathy, thromboembolic event, or cerebral bleed. Delirium was defined as comparatively short course illusions, confusion, and cerebral excitement in the postoperative period. Perioperative myocardial infarction (MI) within 24 h of surgery was defined as creatine phosphokinase-MB ≥5 times the upper limit of normal, with or without new Q waves present in 2 or more contiguous ECG leads. For postoperative MI (>24 h after surgery) at least 1 of the following criteria was used: evolving ST-segment elevations on 12 lead ECG, development of new Q waves in ≥2 contiguous ECG leads, new left bundle-branch block pattern on the ECG, or creatine phosphokinase-MB ≥3 times the upper limit of normal. Heart block was defined as new onset block requiring the implantation of a permanent pacemaker. Postoperative renal failure was defined as acute or worsening renal failure resulting in any one or more of the following: rise in serum creatinine >2.0 mg/dL or doubling of the most recent preoperative serum creatinine or a new requirement for dialysis.
The sample size for the study was calculated from the software G power 3.1.5. G Power (Faul, Erdfelder, Lang, and Buchner, 2007). This is a separate power analysis program available free of charge for windows platform for many statistical tests commonly used in the social, behavioural, and biomedical sciences. It was found that a minimum of 30 patients were required to be recruited in each group for an α value of 5% and keeping the power of the study (1− β) equal to 80%.
All data are presented as mean ± standard deviation. Demographic data were analyzed by Student's t-test. Analysis of variance for repeated measures was used to analyze changes over time. The difference between two different data for each variable was analyzed by Mann–Whitney U-test when statistical significance was found. All the results so obtained have been discussed on 5% level of significance, i.e., P < 0.05 considered statistically significant. IBM SPSS Statistics for Windows, Version 20.0. (Armonk, NY: IBM Corp). has been used to analyze the data.
| Results|| |
With respect to demographic data, there was no statistical difference (P > 0.05) between the study groups [Table 1].
There was a significant difference (P< 0.001) in mean HR between the two groups at all time intervals [Table 2]. In both the groups, mean HR remained largely unaltered at all times in the prebypass period. At 5 min postbypass, mean HR was higher than that of prebypass values. HR declined to prebypass values approximately 30 min post bypass and continued to be so throughout our observation period, i.e., until end of surgery. Overall, mean HR was significantly higher in propofol group compared to dexmedetomidine group.
Inotropic and vasopressor requirements were similar in both the groups. Out of 30 patients in propofol group, 28 patients required hemodynamic support with vasopressors/inotropes, while 27 patients in dexmedetomidine group required vasopressors [Table 3]. The results were statistically insignificant.
MAP was significantly higher in propofol group compared to dexmedetomidine group in prebypass period, during CPB and postbypass period (P< 0.001). There was a significant fall in MAP at the start of CPB (P = 0.018) and a rise in MAP at the termination of CPB (P< 0.001) [Figure 1].
|Figure 1: Line diagram showing comparison of mean arterial pressure (mmHg) between the study groups. Data are expressed as mean ± standard deviation. I = Induction of anesthesia; B +5, B +30, B +60, and B +90 = 5, 30, 60, and 90 min after start of cardiopulmonary bypass respectively. ES = End of surgery|
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For the duration of postoperative ventilation, there was a statistically significant difference between the study groups [Table 4]. In the dexmedetomidine group, the duration of postoperative ventilation was only 5.916 ± 4.30 h compared to 8.566 ± 4.24 in the propofol group (P = 0.019). The duration of ICU stay was shorter in the dexmedetomidine group where it was 92.80 ± 40.71 h compared to 133.46 ± 48.73 h in the propofol group (P< 0.001). Regarding postoperative complications such as MI, stroke, coma, heart block, and renal failure, there was no statistical difference between the study groups. However, the occurrence of delirium was significantly less in the dexmedetomidine group (P = 0.022). None of the patients were excluded from the study due to hemodynamic alterations. All the participating subjects continued throughout the study, and no deaths took place.
| Discussion|| |
In our study, there was a statistically significant difference in mean HR and arterial pressure between the two groups at all time intervals. Kunisawa et al. conducted a study, in which they found lower percentage increase in all hemodynamic parameters, i.e., HR, SBP, and diastolic blood pressure at skin incision or sternotomy in dexmedetomidine group compared to control group. Tosun et al. found that MAPs tended to be lower in the dexmedetomidine group compared to control group (P< 0.05). Jalonen et al. used dexmedetomidine as an anesthetic adjunct in coronary artery bypass grafting patients. They reported that dexmedetomidine significantly blunted the systolic arterial pressure and HR responses to intubation and skin incision and decreased the incidence of tachycardia and hypertension during the surgery. A biphasic effect on hemodynamics is seen after intravenous dexmedetomidine, an immediate increase in systemic arterial pressure (mediated by stimulation of peripheral α2-- adrenoceptors) followed by a longer-lasting reduction in pressure caused by stimulation of α2-- adrenoceptors in the central nervous system. The initial pressor effect is influenced by the rate of intravenous infusion. By infusing dexmedetomidine over 10 min, we saw no increase in SBP. Dexmedetomidine-based therapy led to a predictable and acceptable hemodynamic and cardiovascular profile. The concomitant bradycardia was not clinically significant, with no associated increase in inotropic or pacing requirements and no premature cessation of dexmedetomidine infusion. Martin et al. conducted a study on 401 postsurgical patients, in which they found that continuous dexmedetomidine infusion, with a 1.0 μg/kg loading dose over 10 min, did not increase the risk of cardiovascular complications in patients with presurgical history of hypotension, hypertension, bradycardia, or tachycardia. Increases in SBP and HR have been shown to be causally related to perioperative ischemia in patients with cardiovascular disease. Laryngoscopy and tracheal intubation as well as emergence from anesthesia are known to be particularly dangerous periods for patients with ischemic heart disease. In our study, decreased pressor response to intubation was seen in the dexmedetomidine patients together with the lesser increase in HR compared to propofol group. Both the groups had similar vasopressor and inotropic requirement which can be explained in view of multiple factors such as preoperative cardiac status, surgical correction, cross-clamping time, cardioplegia, etc., that can influence intraoperative hemodynamic outcomes.
Our results showed that dexmedetomidine reduced the length of mechanical ventilation. Afanador et al. reported that intraoperative use of dexmedetomidine as coadjuvant of fentanyl-isoflurane-based anesthesia for elective heart surgery in adult patients could facilitate early postoperative tracheal extubation (197 ± 118 min in dexmedetomidine cohort vs. control 314 ± 265 min, P = 0.002). Abdel-Meguid  reported statistically shorter extubation times with intraoperatively administered dexmedetomidine during off-pump coronary artery bypass grafting. The findings of these studies are in agreement with those of our study. The benefits of dexmedetomidine on achievement of early extubation when compared with propofol could be due to the lack of effect of dexmedetomidine on the suppression of respiratory drive. Other potential reasons for the benefits of dexmedetomidine sedation on early extubation include sympatholytic activity and decreased opioid requirements. The previous studies in surgical patients have shown decreased opioid requirements, supporting this claim.
ICU stay was significantly shorter in the dexmedetomidine group compared with the propofol group. The previous trials showed that dexmedetomidine facilitates early discharge of patients from the ICU following cardiac surgery., Although we did not investigate the total ICU costs in our study, we can say that because of the shorter ICU stay in the dexmedetomidine group, the total ICU cost might be lower than in the propofol group. In the study done by Dasta et al., who investigated the total ICU costs between patients receiving dexmedetomidine versus those receiving midazolam for se dation in ICU, it was shown that the ICU costs were lower in the dexmedetomidine group, although the ICU stay was not significantly lower than in the midazolam group.Taking into account its high incidence, the occurrence of delirium places a huge burden on healthcare systems, patients themselves and their families, because of the higher morbidity rates, decline in long-term cognitive function, higher monetary cost, and increased mortality., From a retrospective cohort study containing 1134 cardiac surgery patients, perioperative use of dexmedetomidine has been shown to be related to a lower risk of delirium (adjusted odds ratio, 0.53; 95% confidence interval 0.37, 0.75). In our study, similar outcomes showing that dexmedetomidine compared to propofol may significantly reduce the risk of postoperative delirium can be concluded. At present, the exact mechanism by which dexmedetomidine reduces the risk of delirium and the pathophysiologic mechanism of delirium remains poorly understood. Several studies, however, consider this benefit to be related to the gamma-aminobutyric acid receptor-sparing activity, minimal respiratory depression, normal sleep-mimicking effect, lack of anticholinergic activity, and the opioid-sparing effect., These results are in accordance with our study, indicating that perioperative use of dexmedetomidine may be a good choice for attenuating the delirium following cardiac surgery.
There are some limitations in the present study. These include the limited number of patients and the critical cases, patients with borderline or poor contractility, and those with critical coronary lesions, who were excluded from the study. When dexmedetomidine is administered to these patients, they are at high risk for developing bradycardia and hypotension. Because of limited resources at our hospital, the drug infusions were stopped at the end of surgery, and the postoperative findings can only suggest the effects of dexmedetomidine. In addition, serum concentrations of dexmedetomidine and propofol were not measured. Thus, we were only able to describe the association of clinical variables with predicted but not measured drug concentrations. It should be noted that further studies with larger samples are warranted to perform a multivariate analysis to better define advantages and disadvantages of dexmedetomidine on intraoperative hemodynamics, postoperative complications as well as its effect on reducing ICU stay in patients undergoing cardiac surgery.
| Conclusions|| |
This study evaluated dexmedetomidine versus propofol for sedation in patients during cardiac surgery with CPB. From our study, we can conclude that the perioperative infusion of dexmedetomidine in patients undergoing cardiac surgery may be superior to propofol anesthesia because dexmedetomidine produces better hemodynamic stability, reduces the risk of postoperative delirium, and leads to shorter ICU stay.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]