|Year : 2015 | Volume
| Issue : 2 | Page : 16-23
Effects of dexmedetomidine versus morphine on surgical stress response and analgesia in postoperative open cardiac surgery
Said M Al-Medani1, Fawzi A Neemat-Allah1, Mohamed M El-Sawy2, Ragab S Beltagi1, Mohamed H Osman1
1 Department of Anaesthesia and Surgical Intensive Care, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
2 Department of Clinical and Chemical Pathology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
|Date of Submission||22-Oct-2014|
|Date of Acceptance||18-Nov-2014|
|Date of Web Publication||30-Dec-2016|
Mohamed H Osman
Department of Anaesthesia and Surgical Intensive Care, Alexandria University, Alexandria
Source of Support: None, Conflict of Interest: None
The aim of this study was to compare between dexmedetomidine and morphine for use as sedative/analgesics and to evaluate their effects on surgical stress response during the first 24 h following open cardiac surgery in the Cardiac Intensive Care Unit (CICU).
Patients and methods
The present double-blind study was carried out on 30 adult patients 60 years of age or older admitted to the Cardiothoracic Surgery Department of the Alexandria Main University Hospital of ASA physical status grade II and III, scheduled for elective coronary artery bypass grafting surgery under general anesthesia. Immediately after sternal closure at the end of surgery, patients were classified randomly using the closed-envelope technique into two equal groups, started immediately on a continuous intravenous infusion (without a loading dose) of either dexmedetomidine or morphine and continued for 24 h postoperatively. Dexmedetomidine group (group D): dexmedetomidine was prepared at a concentration of 0.1 μg/kg/ml and was infused at a dose of 0.1-0.7 μg/kg/h (equivalent to an infusion rate of 1-7 ml/h). Morphine group (group M): morphine was prepared at a concentration of 10 μg/kg/ml and was infused at a dose of 10-70 μg/kg/h (equivalent to an infusion rate of 1-7 ml/h). Patients were followed up in the CICU for the first 24 h following open cardiac surgery on the basis of hemodynamic changes, plasma interleukin (IL)-6 and cortisol levels, time to successful tracheal extubation, postoperative pain, incidence of delirium, and postoperative nausea and vomiting.
The mean heart rate values were significantly lower in group D compared with group M during most of the postoperative period. The mean values of systolic blood pressure, diastolic blood pressure, and mean arterial pressure, on comparing the two groups, had showed no statistically significant difference during the entire postoperative period. The mean values of IL-6, cortisol, and glucose were increased significantly in group M relative to group D at 6 and 24 h postoperatively. Time to successful tracheal extubation was significantly shorter in patients of group D than in patients of group M. Visual analogue scale for pain score and Motor Activity Assessment Scale for sedation score showed no significant difference when both groups were compared during the entire postoperative period. The total number of patients with delirium was significantly fewer in group D than group M. The incidences of nausea and vomiting events were insignificantly lower in group D than group M.
The administration of dexmedetomidine exerted a potent negative chronotropic effect with decreased heart rate. Both dexmedetomidine and morphine equivalently decreased the blood pressure (systolic blood pressure, diastolic blood pressure, and mean arterial pressure) in a range of 15-20% in relation to the preoperative readings. Dexmedetomidine significantly attenuated the surgical stress response and the neuroendocrine response in comparison with morphine through the suppression of the postoperative increase of IL-6 and cortisol, respectively. Dexmedetomidine had promoted earlier recovery and tracheal extubation than morphine, with no accompanying respiratory depression. Both dexmedetomidine and morphine were efficient sedative/analgesics for postoperative cardiac surgery. Dexmedetomidine significantly reduced the incidence and duration of delirium after cardiac surgery.
Keywords: Cytokines, cardiopulmonary bypass (CPB), dexmedetomidine, inflammation
|How to cite this article:|
Al-Medani SM, Neemat-Allah FA, El-Sawy MM, Beltagi RS, Osman MH. Effects of dexmedetomidine versus morphine on surgical stress response and analgesia in postoperative open cardiac surgery. Res Opin Anesth Intensive Care 2015;2:16-23
|How to cite this URL:|
Al-Medani SM, Neemat-Allah FA, El-Sawy MM, Beltagi RS, Osman MH. Effects of dexmedetomidine versus morphine on surgical stress response and analgesia in postoperative open cardiac surgery. Res Opin Anesth Intensive Care [serial online] 2015 [cited 2020 Feb 26];2:16-23. Available from: http://www.roaic.eg.net/text.asp?2015/2/2/16/161316
| Introduction|| |
Surgery induces a variety of metabolic, endocrine, and immune changes known as the 'stress response', which may lead to prolonged in-hospital stay. The clinical manifestations of this reaction include postoperative complications such as respiratory failure, wound infections, myocardial damage with contractile dysfunction, renal impairment, coagulopathy, neurologic dysfunction, and altered liver function with an increased mortality .
Inflammatory response in cardiac surgical patients is produced by complex interactions with numerous pathways including generation or activation of complement, cytokines, neutrophils, thrombin, mast cells, and other multiple inflammatory mediators. Cardiopulmonary bypass (CPB) responses have often been compared with the pathophysiologic changes occurring in systemic inflammatory response syndrome . Cytokines are immune mediators that direct the inflammatory response to sites of injury and infection and are essential for wound healing. An exaggerated production of proinflammatory cytokines from the primary site of injury, however, can manifest systemically as hemodynamic instability or metabolic derangements. Interleukin (IL)-6 is a main proinflammatory cytokine produced as early as 2-4 h after tissue damage. Circulating IL-6 levels appear to be proportional to the extent of tissue injury during an operation .
The metabolic effects of cortisol serve to overcome the stressful state. Cortisol exerts widespread effects on the metabolism and utilization of glucose, amino acids, and fatty acids in hepatic and extrahepatic tissues .
Dexmedetomidine is an α2-adrenergic agonist that is the pharmacologically active dextroisomer of medetomidine. It activates receptors in the medullary vasomotor center, reducing norepinephrine turnover and decreasing central sympathetic outflow, resulting in alterations in sympathetic function . Dexmedetomidine exerts complex hemodynamic effects specific to its activation of presynaptic and postsynaptic α2-adrenergic receptors. These effects are dose dependent and biphasic: vasodilation at lower dosages, vasoconstriction at higher dosages, and an initial short-term increase in blood pressure, followed by a longer lasting reduction in blood pressure and heart rate (HR) . One of the mechanisms of the anti-inflammatory effects of dexmedetomidine may be by modulation of cytokine production through reduction in the proinflammatory mediators IL-1b, IL-6, and tumor necrosis factor-a (TNF-a) .
Dexmedetomidine has analgesic properties and other advantageous pharmacological effects that make it a potentially useful and safe adjunct in several clinical applications . Both hypnotic and supraspinal analgesic effects of dexmedetomidine are mediated by noradrenergic neurons. Dexmedetomidine causes inhibition of norepinephrine release and its neuron-associated activity in the descending medullospinal noradrenergic pathway and suppresses neuronal activity in the locus coeruleus .
The pathogenesis of postoperative delirium is not completely clear, but appears to be related, in part, to increased release of inflammatory mediators and the binding to the γ-aminobutyric acid (GABA) receptor . Dexmedetomidine does not bind to the GABA receptor and hence may minimize the development of delirium by decreasing the release of norepinephrine. The neuroprotective activities of dexmedetomidine were supposed to be caused by inactivation of presynaptic α2-adrenergic receptors, inhibiting noradrenergic activity ,.
| Patients and methods|| |
After approval of the medical ethics committee, an informed written consent was obtained from all patients. This present double-blind study was carried out on 30 adult patients 60 years of age or older admitted to the Cardiothoracic Surgery Department of the Alexandria Main University Hospital of ASA physical status grades II and III scheduled for elective coronary artery bypass grafting (CABG) surgery. Patients with excessive bleeding requiring reoperation, BMI more than 35 kg/m 2 , with a history of obstructive sleep apnea, uncontrolled diabetes, preoperative dementia, parkinsonian disease or recent seizures, chronic pain therapy, and allergy to the study drugs were excluded from the study.
Patients were classified randomly using the closed-envelope technique into two equal groups starting immediately after sternal closure at the end of surgery on a continuous intravenous infusion (without a loading dose) of either dexmedetomidine or morphine and continued for 24 h postoperatively. Dexmedetomidine group (group D): dexmedetomidine was prepared at a concentration of 0.1 μg/kg/ml and was infused at a dose of 0.1-0.7 μg/kg/h (equivalent to an infusion rate of 1-7 ml/h). Morphine group (group M): morphine was prepared at a concentration of 10 μg/kg/ml and was infused at a dose of 10-70 μg/kg/h (equivalent to an infusion rate of 1-7 ml/h).
HR, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were recorded before induction of anesthesia, immediately after the end of surgery, postoperatively during the first 24 h, every 30 min during the first 2 h, every 1 h during the next 6 h, and every 2 h for 16 h. Blood glucose level, plasma level of IL-6, and plasma cortisol level were measured before induction of anesthesia, immediately before dexmedetomidine/morphine infusion, and 6 and 24 h postoperatively. Recovery profile was assessed by measuring time to successful tracheal extubation. Postoperative pain was assessed using the visual analogue scale (VAS)  recorded hourly over 24 h beginning from the patient's transfer to the Cardiac Intensive Care Unit (CICU). Sedation status was assessed using Motor Activity Assessment Scale (MAAS)  recorded hourly over 24 h beginning from the patient's transfer to the CICU. The incidence of postoperative delirium was determined by the validated Confusion Assessment Method for Intensive Care (CAM-ICU)  performed once daily before mid-day. Hemodynamic adverse effects including hypotension (SBP<90 mmHg) and bradycardia (HR<55 beats/min), hyperglycemia (>180 mg/dl), incidence of postoperative nausea and vomiting were observed in both groups.
Data were analyzed using the statistical package for the social sciences (SPSS; SPSS Inc., Chicago, Illinois, USA) software for personal computers using a 't' test, ANOVA test, and χ2 -test. Data were expressed as mean ± SD and P value of 0.05 or less was considered significant.
| Results|| |
There was no statistically significant difference between the two groups in age, sex distribution, body weight, body height, BMI, and durations of operation, CPB, and aortic cross clamping (P > 0.05).
The mean HR values showed no significant difference between both groups in the preoperative readings (P = 0.062). There was no significant difference in the mean HR values between both groups relative to the preoperative readings immediately postoperatively (P = 0.244). The mean HR values were significantly lower in group D relative to group M at 0.5 h and subsequently during the remaining postoperative period (P ≤ 0.05) [Figure 1]. In terms of the mean values of SBP, DBP, and MAP, both groups showed a significant decrease during most of the postoperative period relative to the preoperative base values (P ≤ 0.05); comparison of the two groups showed no statistically significant difference during the entire postoperative period (P > 0.05) [Figure 2].
|Figure 1: Comparison between the two groups studied according to heart rate (beats/min).|
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|Figure 2: Comparison between the two groups studied according to the mean blood pressure (mmHg).|
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In group D, the mean values of IL-6 were increased significantly relative to the preoperative mean value (5.21 ± 1.45 pg/ml), immediately postoperatively, with a mean value of 42.65 ± 6.81 pg/ml (P ≤ 0.001), 6 h postoperatively, with a mean value of 81.31 ± 7.36 pg/ml (P ≤ 0.001), and 24 h postoperatively, with a mean value of 119.25 ± 11.07 pg/ml (P 0≤ 0.001). In group M, the mean values of IL-6 were increased significantly relative to the preoperative mean value immediately postoperatively, with a mean value of 43.20 ± 5.84 pg/ml (P ≤ 0.001), 6 h postoperatively, with a mean value of 132.68 ± 7.85 pg/ml (P ≤ 0.001), and 24 h postoperatively, with a mean value of 231.05 ± 16.11 pg/ml (P ≤ 0.001). There was no statistically significant difference between the two groups in the mean values of IL-6 at the preoperative base level (P = 0.443) and immediately postoperatively (P = 0.813), whereas at 6 and 24 h postoperatively, the mean values of IL-6 were increased significantly in group M relative to group D (P ≤ 0.001) [Figure 3].
|Figure 3: Comparison between the two groups studied in the interleukin-6 level (pg/dl).|
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On comparing both groups, there was no statistically significant difference in the mean values of cortisol and glucose immediately postoperatively (P > 0.05), whereas at 6 and 24 h postoperatively, the mean values of cortisol and glucose were increased significantly in group M relative to group D (P ≤ 0.05).
Time to successful tracheal extubation was significantly shorter in patients of group D (mean 495.40 ± 45.34 min) than in patients of group M (mean 567.13 ± 63.24 min) (P ≤ 0.05).
In the present study, there was no statistically significant difference between the two groups in the VAS during the entire postoperative period (P > 0.05). There was no statistically significant difference between the two groups in the total number of reported pain intensity according to VAS (P > 0.05) [Table 1]. The total dose of additional propofol requirements was lower in group D (125 mg) relative to that in group M (175 mg), but with no statistically significant difference (P > 0.05). The total number of patients who needed additional propofol in group D (20%) was less than that in group M (33%), but there was no significant difference (P > 0.05).
|Table 1 Comparison between the two groups studied in the total number of reported pain intensity according to visual|
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There was no statistically significant difference between the two groups in the MAAS during the entire postoperative period (P > 0.05). There was no statistically significant difference between group D (73.6%) and group M (75.5%) in the total number of recorded values within the target range (2-4) in MAAS (P > 0.05) [Table 2].
|Table 2 Comparison between the two studied groups according to the total number of recorded values within the arget range (2– 4) in Motor Activity Assessment Scale|
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The total number of patients with delirium in group D was two (13.3%), whereas that in group M was eight (53.3%). There was a statistically significant difference between the two groups in the total number of patients with delirium (P = 0.020).
There was a statistically insignificant decrease in the incidence of postoperative nausea and vomiting in patients of group D relative to those in group M.
| Discussion|| |
Although CABG surgery with CPB prolongs life and reduces symptoms in patients with severe coronary artery diseases, these benefits are accompanied by increased risks. Morbidity associated with CPB can be attributed to the generalized inflammatory response induced by blood xenosurface interactions during extracorporeal circulation and the outcomes of ischemia/reperfusion, including exacerbated inflammatory response resembling the systemic inflammatory response syndrome .
The use of specific anesthetic drugs that could, as anti-inflammatory agents, modulate these inflammatory responses and promote a postoperative recovery may be advantageous. It is known that the stress response to surgery can be attenuated by sympatholytic effects caused by activation of the central α2-adrenergic receptor, leading to reductions in blood pressure and HR, and more recently, that they can have anti-inflammatory properties. This study showed some of the clinical significance of the use of dexmedetomidine, a selective α2-adrenergic agonist, as a coadjuvant in the postoperative management. Actually, use of dexmedetomidine is not part of the anesthesia routine, but this drug can be considered a particularly promising agent in perioperative multiple organ protection .
In group M, the mean HR values showed no significant difference in the postoperative period relative to the preoperative base level. In group D, the mean HR values were significantly decreased during the postoperative period relative to the preoperative base level. In comparison with group M, the mean HR values were significantly lower in group D during most of the postoperative period; bradycardia (HR<55 beats/min) was reported twice and was treated by intravenous atropine. In terms of the mean values of SBP, DBP, and MAP, both groups showed a significant decrease during most of the postoperative period relative to the preoperative base values; comparison of the two groups showed no statistically significant difference during the entire postoperative period. The basic effects of dexmedetomidine on the cardiovascular system are a decrease in HR and systemic vascular resistance, with an indirect decrease in myocardial contractility, cardiac output, and systemic blood pressure . In agreement with the present study, Abd Aziz et al.  evaluated in their study the hemodynamic profile of dexmedetomidine infusion compared with morphine infusion in CABG patients for 24 h postoperatively. They found that the mean HR had decreased significantly in the dexmedetomidine group compared with the morphine group (P = 0.028). The mean MAP had decreased in both groups relative to preoperative measurements, but with no statistically significant difference between them postoperatively (P = 0.651). They attributed the decreased HR and MAP with dexmedetomidine to its central effect by a decrease in central sympathetic outflow; MAP reduction in the morphine group was because of the decrease in catecholamine and the direct vasodilation effect of morphine. Arain et al.  compared the effect of dexmedetomidine and morphine on the hemodynamic profile after a major inpatient surgery. They reported that early postoperative HR was significantly slower in the dexmedetomidine-treated patients and that both drugs decreased postoperative MAP, but there were no significant differences between the treatment groups. In contrast to the present study, Aantaa et al.  studied the effect of dexmedetomidine in minor gynecologic surgery and found that the administration of dexmedetomidine did not significantly decrease the HR compared with the control group.
Changes of interleukin-6
On comparing both groups, there was no statistically significant difference in the mean IL-6 values immediately postoperatively, whereas at 6 and 24 h postoperatively, the mean values of IL-6 were increased significantly in group M relative to group D. In agreement with the present study, Tasdogan et al.  carried out a study to compare the effects of an intravenous infusion of propofol and dexmedetomidine on inflammatory responses and intra-abdominal pressure in severe sepsis after abdominal surgery. Dexmedetomidine infusion decreases TNF-a, IL-1, and IL-6 levels and intra-abdominal pressure significantly more than a propofol infusion. Kang et al.  reported the anti-inflammatory effects of dexmedetomidine in patients subjected to laparoscopic cholecystectomy. Patients in the dexmedetomidine group received a loading dose of dexmedetomidine (1.0 μg/kg), followed by an infusion of dexmedetomidine at 0.5 μg/kg/h. Dexmedetomidine decreased the plasma level of IL-1b, TNF-a, IL-6, and IL-10 compared with the saline group. Murphy et al.  carried out a study to evaluate the effects of morphine and fentanyl on the inflammatory response to CPB in patients undergoing elective CABG surgery. The results from this study showed that the use of morphine, compared with fentanyl, can attenuate the release of inflammatory cytokines (IL-6), produce a greater reduction in adhesion molecule expression (CD11b/CD18), and reduce the incidence of postoperative hyperthermia in patients undergoing CPB. Interestingly, Crozier et al.  showed that opioids recued the IL-6 response compared with inhalational anesthesia, whereas Taylor et al.  showed no effect of opioids on IL-6 release. These contrasting results may be explained because there is evidence that opioids exert differentiated immunological effects .
Changes of cortisol and glucose
On comparing both groups, there was no statistically significant difference in the mean cortisol and glucose values immediately postoperatively, whereas at 6 and 24 h postoperatively, the mean values of cortisol and glucose increased significantly in group M relative to group D. Venn et al.  carried out a study to evaluate the effects of dexmedetomidine on adrenal cortical function, cardiovascular, endocrine, and inflammatory responses in postoperative patients requiring sedation in the ICU. They concluded that dexmedetomidine inhibited cortisol synthesis at supra therapeutic concentrations and decreased the inflammatory response to surgical trauma. Mukhtar et al.  found that dexmedetomidine inhibited the hyperglycemic response to surgery significantly more than placebo, and this may reflect attenuation of sympathoadrenal response. McDonald et al.  reported in their study the suppressant effect of therapeutic doses of morphine on the hypothalamic-pituitary-adrenal axis in humans. In contrast to the present study, Pandharipande et al.  measured cortisol concentrations at baseline and 2 days after stopping dexmedetomidine infusion, and there was no statistically significant difference in cortisol concentrations.
Time to successful tracheal extubation
Time to successful tracheal extubation was significantly shorter in patients of group D than in patients of group M. Successful extubation after cardiac surgery is a clinically defining event after which de-escalation of dependency and discharge from ICU becomes possible. Spontaneous breathing trials and intermittent mandatory ventilation are common techniques utilized to expedite the ventilator weaning process. These techniques often require the reduction and/or discontinuation of sedatives and analgesics. However, anxiety, fear, and agitation are among the most common nonpulmonary causes of failure to wean from mechanical ventilation . In a similar study, Abd Aziz et al.  compared in their study the recovery profile of dexmedetomidine and morphine in postoperative cardiac surgery patients and they found that the dexmedetomidine group showed shorter extubation time than the morphine group. In an earlier study, Herr et al.  suggested a potential ventilatory benefit for dexmedetomidine-based sedation after cardiac surgery, where fewer patients required ventilation beyond 8 h. Arpino et al.  used an infusion of dexmedetomidine in a group of mechanically ventilated patients who failed previous attempts at weaning and extubation secondary to agitation. After initiation of dexmedetomidine, 65% of the patients were extubated successfully. In a similar study, Shehabi et al.  reported a success rate of 73%. In contrast to the present study, Koroglu et al.  reported that there is no difference in the recovery time between the use of dexmedetomidine and propofol. These conflicting results for recovery times can be attributed to one of the most interesting properties of dexmedetomidine, which is the ability to achieve sedation with preserved arousability, thus rendering assessment of recovery time to be more subjective rather than objective .
Postoperative pain and sedation status
VAS for pain score and MAAS for sedation score showed no significant difference when both groups were compared during the entire postoperative period. Sedation and analgesia, used to reduce stress response and provide anxiolysis and pain relief, are important components of postoperative management following cardiac surgery . Abd Aziz et al.  carried out a randomized-controlled open-label study to evaluate the efficacy measures of dexmedetomidine versus morphine in postoperative cardiac surgery patients. The efficacy measures for sedation and analgesia were based on the Modified Ramsay Score and the Numeric Pain Intensity Scale, respectively. The results of the efficacy measures were as follows: the median Modified Ramsay Score (2 vs. 3), median Numeric Pain Intensity Scale (1 vs. 2), additional sedative/analgesic, and extubation time were favorable for the dexmedetomidine group compared with the morphine group. Herr et al.  carried out a randomized open-label study on 295 adult patients undergoing CABG surgery to compare dexmedetomidine-based with propofol-based sedation postoperatively. The results showed that the mean sedation levels were within the target ranges in both groups. The mean times to weaning and extubation were similar, although fewer dexmedetomidine patients remained on the ventilator beyond 8 h. The use of morphine was significantly reduced in the dexmedetomidine group. Only 28% of the dexmedetomidine patients required morphine for pain relief while ventilated versus 69% of propofol-based patients. Propofol patients required 4 times the mean dose of morphine while in the ICU. They concluded that dexmedetomidine provided safe and effective sedation for post-CABG surgical patients and significantly reduced the use of analgesics, b-blockers, antiemetics, epinephrine, and diuretics.
In the present study, the total number of patients with delirium was significantly fewer in group D than group M. In a similar study, Shehabi et al.  conducted a randomized double-blinded controlled clinical trial to evaluate the prevalence of delirium with dexmedetomidine compared with morphine-based therapy after cardiac surgery. A total of 306 patients at least 60 years of age were randomized to receive dexmedetomidine (0.1-0.7 μg/kg/h) or morphine (10-70 μg/kg/h), with open-label propofol titrated to a target MAAS of 2-4. Both dexmedetomidine-based and morphine-based therapy achieved adequate and equivalent analgesia and sedation. They observed a 42.9% significant reduction in the incidence of delirium with dexmedetomidine, with a significant reduction in the duration of postoperative delirium compared with morphine. Several specific characteristics of dexmedetomidine may account for this effect. First, dexmedetomidine has high and specific receptor selectivity. Studies have suggested that the likelihood of delirium is increased with the number of neurotransmitter pathways disrupted . The second characteristic is its effect in presynaptic noradrenergic transmission. Changes in the noradrenergic system have been described as potential causative factors in delirium, with increased levels of plasma free-MHPG (3-methoxy-4-hydrophenylglycol) concentration observed in some delirium states . Third, dexmedetomidine produces sedation without respiratory depression . Studies have reported that hypoxia and anoxia in the CNS are critical events leading to the biomolecular derangements in delirium . Aakerlund and Rosenberg  reported lower postoperative oxygen-saturation in post-thoracotomy patients who developed delirium compared with patients who did not develop delirium, with the resolution of mental status changes after oxygen supplementation. Fourth, dexmedetomidine lacks clinically significant anticholinergic effects . A strong association has been documented between medications with anticholinergic potential and the development of delirium . Fifth, dexmedetomidine is believed to promote a more physiologic sleep-wake cycle in the ICU setting. This is important because sleep deprivation and disruption have been implicated in the onset and perpetuation of delirium . Sixth, dexmedetomidine has been shown to exert neuroprotective effects in humans undergoing cardiac surgery . Finally, several studies have suggested that postoperative patients sedated with dexmedetomidine have lower opioid requirements, an average of 40% lower . This is significant because studies have reported a direct relationship between opiate use and development of delirium .
Postoperative nausea and vomiting
The number of nausea and vomiting events was fewer in group D than group M, although there was no statistically significant difference between the two groups in the incidence of postoperative nausea and vomiting. In agreement with the present study, Gurbet et al.  evaluated the impact of an intra-operative dexmedetomidine infusion on morphine requirements postoperatively in 50 women undergoing total abdominal hysterectomy. Patients in the dexmedetomidine group reported less nausea than patients in the placebo group. Lin et al.  carried out a double-blinded, randomized, controlled study to examine whether dexmedetomidine added to intravenous patient-controlled analgesia morphine could improve analgesia while reducing opioid-related side effects. One hundred women undergoing abdominal total hysterectomy were allocated to receive morphine (group M) or morphine plus dexmedetomidine (group D) for postoperative intravenous patient controlled analgesia (PCA). They found that the incidence of nausea during the 4-24 h period was significantly lower in group D than in group M. Furthermore, the overall incidence of severe nausea was significantly lower in group D than in group M. The incidence of vomiting during the 4-24 h and the overall incidence of severe vomiting were also lower in group D than in group M, but the differences were not significant. This study had shown that the dexmedetomidine-morphine mixture significantly enhances the analgesic effect of morphine, reduces PCA morphine requirements, and decreases the coexisting morphine-induced nausea and vomiting.
From the present study, we concluded that the administration of dexmedetomidine is recommended in postoperative cardiac surgery patients. It ensure patients' safety through hemodynamic stability, efficient analgesia, predicted sedation with no respiratory depression, ensures early recovery profile, reduced stress/neuroendocrine responses, and decreased incidence of postoperative delirium, nausea, and vomiting.
| Acknowledgements|| |
Conflicts of interest
| References|| |
Sander M, von Heymann C, von Dossow V, Spaethe C, Konertz WF, Jain U, Spies CD. Increased interleukin-6 after cardiac surgery predicts infection. Anesth Analg 2006; 102:1623-1629.
Wan S, LeClerc JL, Vincent JL. Inflammatory response to cardiopulmonary bypass: mechanisms involved and possible therapeutic strategies. Chest 1997; 112:676-692.
Wei M. Cytokine responses and anti-inflammatory strategies in Coronary Artery Bypass Grafting. Tampere Univ Press, 2001.
Velickovic I, Yan J, Gross JA. Modifying the neuro-endocrine stress response. Semin Anaesth Periop Med Pain 2002; 21:16-25.
Guerlach AT, Dasta JF. Dexmedetomidine: an updated review. Ann Pharmacother 2007; 41:245-252.
Ebert TJ, Hall JE, Barney JA, Uhrich TD, Colinco MD. The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology 2000; 93:382-394.
Hofer S, Steppan J, Wagner T, Funke B, Lichtenstern C, Martin E, et al
. Central sympatholytics prolong survival in experimental sepsis. Crit Care 2009; 13:R11.
Sleigh J. All hands on dexmedetomidine. Anaesthesia 2012; 67:1193-1197.
Ishii H, Kohno T, Yamakura T, Ikoma M, Baba H Action of dexmedetomidine on the substantia gelatinosa neurons of the rat spinal cord. Eur J Neurosci 2008; 27:3182-3190.
Maldonado Jr, Wysong A, van der Starre PJ, Block T, Miller C, Reitz BA Dexmedetomidine and the reduction of postoperative delirium after cardiac surgery. Psychosomatics 2009; 50:206-217.
Peng L, Yu AC, Fung KY, Prévot V, Hertz L. Alpha-adrenergic stimulation of ERK phosphorylation in astrocytes is alpha(2)-specific and may be mediated by transactivation. Brain Res 2003; 978:65-71.
Li B, Du T, Li H, Gu L, Zhang H, Huang J, et al
. Signalling pathways for transactivation by dexmedetomidine of epidermal growth factor receptors in astrocytes and its paracrine effect on neurons. Br J Pharmacol 2008; 154:191-203.
Kindler CH, Harms C, Amsler F, Ihde-Scholl T, Scheidegger D. The visual analog scale allows effective measurement of preoperative anxiety and detection of patients′ anesthetic concerns. Anesth Analg 2000; 90:706-712.
Devlin JW, Boleski G, Mlynarek M, Nerenz DR, Peterson E, Jankowski M, et al
. Motor Activity Assessment Scale: a valid and reliable sedation scale for use with mechanically ventilated patients in an adult surgical intensive care unit. Crit Care Med 1999; 27:1271-1275.
Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, et al
. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA 2001; 286:2703-2710.
Bulow NMH, Colpo E, Duarte MF, Correa EFM, Schlosser RS, Lauda A et al.
Inflammatory response in patients under coronary artery bypass grafting surgery and clinical implications: a review of the relevance of dexmedetomidine use. ISRN Anesthesiol 2014; 2014:905238.
Hogue CW Jr, Talke P, Stein PK, Richardson C, Domitrovich PP, Sessler DI. Autonomic nervous system responses during sedative infusions of dexmedetomidine. Anesthesiology 2002; 97:592-598.
Abd Aziz N, Chue MC, Yong CY, Hassan Y, Awaisu A, Hassan J, Kamarulzaman MH. Efficacy and safety of dexmedetomidine versus morphine in post-operative cardiac surgery patients. Int J Clin Pharm 2011; 33:150-154.
Arain SR, Ruehlow RM, Uhrich TD, Ebert TJ. The efficacy of dexmedetomidine versus morphine for postoperative analgesia after major inpatient surgery. Anesth Analg 2004; 98:153-158.
Aantaa R, Kanto J, Scheinin M, Kallio A, Scheinin H. Dexmedetomidine, an alpha 2-adrenoceptor agonist, reduces anesthetic requirements for patients undergoing minor gynecologic surgery. Anesthesiology 1990; 73:230-235.
Tasdogan M, Memis D, Sut N, Yuksel M Results of a pilot study on the effects of propofol and dexmedetomidine on inflammatory responses and intraabdominal pressure in severe sepsis. J Clin Anesth 2009; 21:394-400.
Kang SH, Kim YS, Hong TH, Chae MS, Cho ML, Her YM, Lee J. Effects of dexmedetomidine on inflammatory responses in patients undergoing laparoscopic cholecystectomy. Acta Anaesthesiol Scand 2013; 57:480-487.
Murphy GS, Szokol JW, Marymont JH, Avram MJ, Vender JS. The effects of morphine and fentanyl on the inflammatory response to cardiopulmonary bypass in patients undergoing elective coronary artery bypass graft surgery. Anesth Analg 2007; 104:1334-1342.
Crozier TA, Müller JE, Quittkat D, Sydow M, Wuttke W, Kettler D Effect of anaesthesia on the cytokine responses to abdominal surgery. Br J Anaesth 1994; 72:280-285.
Taylor NM, Lacoumenta S, Hall GM. Fentanyl and the interleukin-6 response to surgery. Anaesthesia 1997; 52:112-115.
Borgland SL, Connor M, Osborne PB, Furness JB, Christie MJ. Opioid agonists have different efficacy profiles for G protein activation, rapid desensitization, and endocytosis of mu-opioid receptors. J Biol Chem 2003; 278:18776-18784.
Venn RM, Bryant A, Hall GM, Grounds RM. Effects of dexmedetomidine on adrenocortical function, and the cardiovascular, endocrine and inflammatory responses in post-operative patients needing sedation in the intensive care unit. Br J Anaesth 2001; 86:650-656.
Mukhtar AM, Obayah EM, Hassona AM. The use of dexmedetomidine in pediatric cardiac surgery. Anesth Analg 2006; 103:52-56.
McDonald RK, Evans FT, Weise VK, Patrick RW. Effect of morphine and nalorphine on plasma hydrocortisone levels in man. J Pharmacol Exp Ther 1959; 125:241-247.
Pandharipande PP, Pun BT, Herr DL, Maze M, Girard TD, Miller RR, et al
. Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial. JAMA 2007; 298:2644-2653.
Shehabi Y, Nakae H, Hammond N, Bass F, Nicholson L, Chen J. The effect of dexmedetomidine on agitation during weaning of mechanical ventilation in critically ill patients; Anaesth Intensive Care 2010; 38:82-90.
Herr DL, Sum-Ping ST, England M. ICU sedation after coronary artery bypass graft surgery: dexmedetomidine-based versus propofol-based sedation regimens. J Cardiothorac Vasc Anesth 2003; 17:576-584.
Arpino PA, Kalafatas K, Thompson BT. Feasibility of dexmedetomidine in facilitating extubation in the intensive care unit. J Clin Pharm Ther 2008; 33:25-30.
Koroglu A, Demirbilek S, Teksan H, Sagir O, But AK, Ersoy MO. Sedative, haemodynamic and respiratory effects of dexmedetomidine in children undergoing magnetic resonance imaging examination: preliminary results. Br J Anaesth 2005; 94:821-824.
Venn RM, Bradshaw CJ, Spencer R, Brealey D, Caudwell E, Naughton C, et al
. Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit. Anaesthesia 1999; 54:1136-1142.
Jackson DL, Proudfoot CW, Cann KF, Walsh T. A systematic review of the impact of sedation practice in the ICU on resource use, costs and patient safety. Crit Care 2010; 14:R59.
Shehabi Y, Grant P, Wolfenden H, Hammond N, Bass F, Campbell M, Chen J. Prevalence of delirium with dexmedetomidine compared with morphine based therapy after cardiac surgery: a randomized controlled trial (DEXmedetomidine COmpared to Morphine-DEXCOM Study). Anesthesiology 2009; 111:1075-1084.
Maldonado JR. Pathoetiological model of delirium: a comprehensive understanding of the neurobiology of delirium and an evidence-based approach to prevention and treatment. Crit Care Clin 2008; 24:789-856.
Nakamura J, Uchimura N, Yamada S, Nakazawa Y. Does plasma free-3-methoxy-4-hydroxyphenyl(ethylene)glycol increase in the delirious state? A comparison of the effects of mianserin and haloperidol on delirium. Int Clin Psychopharmacol 1997; 12:147-152.
Hsu YW, Cortinez LI, Robertson KM, Keifer JC, Sum-Ping ST, Moretti EW, et al
. Dexmedetomidine pharmacodynamics: part I: crossover comparison of the respiratory effects of dexmedetomidine and remifentanil in healthy volunteers. Anesthesiology 2004; 101:1066-1076.
Seaman JS, Schillerstrom J, Carroll D, Brown TM. Impaired oxidative metabolism precipitates delirium: a study of 101 ICU patients. Psychosomatics 2006; 47:56-61.
Aakerlund LP, Rosenberg J. Postoperative delirium: treatment with supplementary oxygen. Br J Anaesth 1994; 72:286-290.
Buttermann AE, Reid K, Maze M. Are cholinergic pathways involved in the anesthetic response to alpha2 agonists. Toxicol Lett 1998; 100:17-22.
Tune LE, Egeli S. Acetylcholine and delirium. Dement Geriatr Cogn Disord 1999; 10:342-344.
Nelson LE, Lu J, Guo T, Saper CB, Franks NP, Maze M. The alpha2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects. Anesthesiology 2003; 98:428-436.
Wijeysundera DN, Naik JS, Beattie WS. Alpha-2 adrenergic agonists to prevent perioperative cardiovascular complications: a meta-analysis. Am J Med 2003; 114:742-752.
Weinbroum AA, Ben-Abraham R. Dextromethorphan and dexmedetomidine: new agents for the control of perioperative pain. Eur J Surg 2001; 167:563-569.
Maddocks I, Somogyi A, Abbott F, Hayball P, Parker D. Attenuation of morphine-induced delirium in palliative care by substitution with infusion of oxycodone. J Pain Symptom Manage 1996; 12:182-189.
Gurbet A, Basagan-Mogol E, Turker G, Ugun F, Kaya FN, Ozcan B. Intraoperative infusion of dexmedetomidine reduces perioperative analgesic requirements. Can J Anaesth 2006; 53:646-652.
Lin TF, Yeh YC, Lin FS, Wang YP, Lin CJ, Sun WZ, Fan SZ Effect of combining dexmedetomidine and morphine for intravenous patient-controlled analgesia. Br J Anaesth 2009; 102:117-122.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]