Dexmedetomidine as anesthetic adjunct for fast tracking and pain control in off-pump coronary artery bypass.

OBJECTIVE: This study was designed to determine the efficacy of dexmedetomidine (a highly selective alpha-2 agonist) in achieving fast tracking and improved postoperative pain control in off-pump coronary artery bypass (OPCAB) patients.
METHODS: THIRTY PATIENTS SCHEDULED FOR ELECTIVE OPCAB WERE PROSPECTIVELY RANDOMIZED INTO TWO GROUPS: Group I (15 patients) started dexmedetomidine at 0.5 ug/kg/hour after the induction of anesthesia; this was reduced to 0.3 ug/kg/hour on admission in the cardiac intensive care unit and continued for 12 hours post extubation. Group II (15 patients) received a similar volume and infusion rate of normal saline. Visual analog scale (VAS) of 10-100 was explained thoroughly to the patients during the preoperative visit. Postoperative pain was managed with morphine. The total dose of morphine was recorded. Extubation time and VAS was recorded every two hours for 12 hours post extubation.
RESULTS: Extubation time in group I was 72±8 minutes and 186±22 minutes in group II. Mean total use of narcotics in group II was 23.5±20.7 mg compared to 11.4±6.3 mg in group I. VAS median figures were lower at all data points in group I than in group II.
CONCLUSION: Dexmedetomidine showed an effective and safe profile as an anesthetic adjunct in OPCAB, achieving fast tracking of patients and higher quality of pain control with a lower consumption of narcotics.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Dexmedetomidine is a highly selective alpha-2 adrenoceptor agonist that has been shown to have both sedative and analgesic effects.[1] Its plasma half-life is two hours, which makes it ideal for intravenous infusion.[1] Dexmedetomidine exerts electrophysiological effects on neuronal cell membranes affecting ion conductance with subsequent hyperpolarization.[2] Thus, it has the advantages of sedative, analgesic, and anxiolytic actions with hemodynamic and respiratory stability.[2] As dexmedetomidine has the ability to potentiate opioids and other sedatives, this attribute suggests that these drugs can be administered in smaller doses.[3]

Postoperative control of pain is a crucial need for early extubation and fast tracking of off-pump coronary artery bypass (OPCAB) patients. Thus any intervention that could lower the dosage of narcotics used to control postoperative pain while reducing the dosage and proved side effects of opioids is by far the best choice for a cardiac anesthesiologist to achieve the ultimate goal of fast tracking in OPCAB.[4]

The aim of the present study is to determine the effectiveness of dexmedetomidine as an adjunct to anesthetic management in OPCAB in achieving fast tracking and controlling postoperative pain.

METHODS

After approval of the departmental and hospital research review boards, an informed written patient consent was taken from suitable candidates before being enrolled in the study.

This was a prospective controlled observational randomized study, where 30 patients scheduled for elective coronary artery surgery performed by the OPCAB technique were enrolled. Exclusion criteria were mainly those concerning the contraindications for performing the OPCAB technique such as unstable angina, poor left ventricular (LV) function with ejection fraction (EF) <30%, dilated cardiomyopathy, or severely diseased target coronary vessels. Also, any contraindication for the use of the study drug was included, such as heart block and volume-depleted patients. Patients were randomly allocated into two groups. Group I (15 patients) started dexmedetomidine by continuous infusion at 0.5 ug/kg/hour after induction of anesthesia; this was reduced to 0.3 ug/kg/hour on admission to the cardiac intensive care unit (CICU) and continued for 12 hours post extubation. Group II (15 patients) received a similar volume and infusion rate of normal saline, assigned medical staff. Visual analog scale (VAS) of 10-100 was explained thoroughly to the patients during the preoperative visit. VAS was recorded every two hours for 12 hours post extubation and any VAS assessment >40 was managed with an intravenous push of morphine 0.05 mg/kg. All patients received a standard total intravenous anesthetic consisting of midazolam, sufentanil, and rocuronium supplemented with sevoflurane. Postoperative pain was managed with morphine. Total dose of morphine was recorded. Extubation time after fulfilling criteria for weaning off mechanical ventilation and since admission to the CICU was recorded for both groups. Randomization was performed using medical record number of the patients, being odd numbers for group I and even numbers for group II. The anesthetic technique was standardized for both groups; the patients were premedicated with lorazepam 2 mg orally on the night of the surgery and morphine 0.1 mg/kg intramuscular (IM) two hours preoperatively. On receiving the patient in the operating room, ECG, NIABP, O2 Saturation and peripheral venous as well as radial artery cannulation was done. Induction was followed with sufentanil 1-1.5 μg/kg, midazolam 0.05-0.1 mg/kg, and rocuronium 0.9 mg/kg; then, a maintenance infusion of the same induction agents sufentanil 0.2 μg/kg/hour, midazolam 1.5 ug/kg/hour, and rocuronium 0.5 mg/kg/hour were supplemented with sevoflurane through an anesthesia delivery unit (Datex-Ohmeda, type 5). A fiber optic pulmonary artery catheter (7F, Baxter Healthcare, Irvine, California) was inserted after induction of anesthesia enabling continuous monitoring of cardiac output and mixed venous oxygen saturation (SvO2) as well as other derived parameters. The lungs were mechanically ventilated with a tidal volume of 8 mL/kg and fraction of inspired oxygen (FiO2) of 50% oxygen in air mixture, while the ventilatory rate was adjusted to maintain a carbon dioxide partial pressure (PCO2) of 32-36 mmHg.

Statistical analysis

Statistical analysis was performed with the Graphpad Instat 3.05 software package for Windows. Comparison between the two groups at different data points was performed using parametric or nonparametric unpaired t-test as appropriate, where data were expressed as mean ± standard deviation or median (range) as appropriate. Categorical data were compared using Pearson's χ2 test or Fischer's exact test as appropriate; P<0.05 was considered statistically significant.

RESULTS

Demographic data were comparable in both groups including the surgical operation time [Table 1]. Extubation time showed a statistically significant earlier extubation in group I (72±8 minutes), compared to group II (186±22 minutes), with a P<0.05 [Table 2]. Analgesia achieved with VAS median figures were significantly lower at all data points in group I than in group II [Table 3 and Figure 1]. Mean total narcotic use was significantly lower in group I (11.4±6.3 mg) when compared to group II (23.5±20.7 mg) as shown in Table 2.

Table 1

Demographic data

Table 2

Postoperative data figures expressed as mean±SD

Table 3

Visual analog scale figures expressed as median (range)

Figure 1

Trend of postoperative visual analog scale in both groups

DISCUSSION

The special properties of sympatholytic and analgesic effects along with preservation of respiratory function of dexmedetomidine allow the continuation of dexmedetomidine infusion in the extubated, spontaneously breathing patient.[5] Administration of dexmedetomidine as continuous infusion is associated with a predictable and stable hemodynamic response that could be adjusted with titration of the infusion rate being within the range of 0.2-0.7 ug/kg/hour.[6-8] Dexmedetomidine allows sedated patients to be quickly aroused and oriented upon demand, whereas it does not require discontinuation prior to weaning from mechanical ventilation.[578] Also, dexmedetomidine exerts synergistic effects on opioids and other sedatives, which in return leads to reduction in their dosing.[6]

In the present study, dexmedetomidine was started with the initiation of surgery and continued all through till 12 hours after extubation. In spite of the fact previously proved in multiple studies that intaroperative use of dexmedetomidine offers stable hemodynamics with reduction in anesthetic requirements, it was not the target of the study to analyze or to prove this finding. On the other hand, the target of the current study was to prove the effect of such reduction in anesthetic requirements by achieving early extubation and fast tracking of patients. This finding was proved in the current study with a statistically significant earlier extubation in the dexmedetomidine group. Several studies have shown that dexmedetomidine is useful in cardiac surgical patients postoperatively.[78] Presynaptic activation of the alpha-2 adrenoceptor in the locus coeruleus inhibits the release of norepinephrine and results in sedative and hypnotic effects.[34] Stimulation of the alpha-2 adrenoceptors in this area terminates the propagation of pain signals leading to analgesia.[4] At the spinal level, stimulation of alpha-2 receptors at the dorsal horn leads to inhibition of the firing of nociceptive neurons and inhibition of the release of substance P.[4] In the present study, the VAS assessed and recorded in the postextubation period showed lower median values all over the data points. Also, the total consumption of morphine was significantly lower in the dexmedetomidine group than in the other group. Both prove a better quality of analgesia with reduction in the requirements of opioids.

In conclusion, dexmedetomidine as an adjunct to anesthetic management in OPCAB provides a better quality of postoperative analgesia with opioid-sparing effect, while at the same time achieving the ultimate goal in management of OPCAB which is fast tracking of patients.