|Year : 2014 | Volume
| Issue : 2 | Page : 156-162
Intramuscular dexmedetomidine for prevention of shivering after general anesthesia in patients undergoing arthroscopic anterior cruciate ligament reconstruction
Waleed M. Abdelmageed, Waleed M Al Taher
Department of Anesthesia and Intensive Care, Faculty of Medicine, Ain-Shams University, Cairo, Egypt
|Date of Submission||08-Jun-2013|
|Date of Acceptance||03-Oct-2013|
|Date of Web Publication||31-May-2014|
Waleed M Al Taher
Department of Anesthesia and Intensive Care, Faculty of Medicine, Ain-Shams University, Cairo
Source of Support: None, Conflict of Interest: None
Postanesthetic shivering (PAS) can influence hemodynamic stability and recovery from general anesthesia. We tested the efficacy of intramuscular dexmedetomidine in prevention of PAS in patients undergoing arthroscopic anterior cruciate ligament reconstruction.
Materials and methods
In this prospective, randomized, and double-blind controlled study, 85 ASA I male patients, aged 18-40 years, scheduled for arthroscopic anterior cruciate ligament reconstruction under general anesthesia were enrolled. Forty-five minutes before the expected end of surgery, the patients were randomized to receive an intramuscular injection in the deltoid muscle of either dexmedetomidine 2.5 μg/kg (group D, n = 43) or isotonic saline (group C, n = 42). Extubation time, the incidence and grades of shivering, pain intensity, degree of sedation, and side effects were recorded.
The mean ± SD extubation time was prolonged in the dexmedetomidine group than in the control group (8.4 ± 2.3 vs. 7.2 ± 2.6 min, respectively; P = 0.0268). The incidence of shivering was 64.28% in the control group compared with 11.62% in the dexmedetomidine group (P ≤ 0.0001), with lower intensity in group D. Assessment of pain intensity until 2 h postoperatively revealed significantly lower scores in dexmedetomidine-treated patients (P = 0.0239 at the second hour). Sedation scores were higher in the dexmedetomidine group until 4 h postoperatively (P = 0.032 at the fourth hour). The mean heart rates and blood pressure were significantly lower in group D than in group C (P < 0.05) in most of the assessments until 6 h postoperatively.
Intramuscular dexmedetomidine provides effective prophylaxis against PAS without major side effects.
Keywords: Dexmedetomidine, postanesthetic shivering
|How to cite this article:|
Abdelmageed WM, Al Taher WM. Intramuscular dexmedetomidine for prevention of shivering after general anesthesia in patients undergoing arthroscopic anterior cruciate ligament reconstruction. Ain-Shams J Anaesthesiol 2014;7:156-62
|How to cite this URL:|
Abdelmageed WM, Al Taher WM. Intramuscular dexmedetomidine for prevention of shivering after general anesthesia in patients undergoing arthroscopic anterior cruciate ligament reconstruction. Ain-Shams J Anaesthesiol [serial online] 2014 [cited 2021 May 6];7:156-62. Available from: http://www.asja.eg.net/text.asp?2014/7/2/156/133386
| Introduction|| |
Postanesthetic shivering (PAS) can occur in 5-65% of patients recovering from general anesthesia . This unpleasant and potentially serious complication is a result of either intraoperative hypothermia or the effects of anesthetic agents, causing involuntary repetitive contractions of the skeletal muscles . Although the mechanism of shivering is not fully understood, it is common in patients who became hypothermic during surgery . In addition to the cold ambient temperature in the operating theater, high flow rates of unhumidified fresh gases, the use of large volumes of unwarmed intravenous (i.v.) fluids, or intraoperative prolonged exposure of a large surgical wound can also be contributory .
Many pharmacological agents have been investigated for the prevention or treatment of postoperative shivering. Intravenous opioids (meperidine, alfentanil, and nalbuphine) , the cholinomimetic physostigmine , the nonopioid analgesic tramadol , 5-hydroxytryptamine antagonist (ondansetron) , and the adrenergic agonist clonidine  have reduced the incidence of shivering or suppressed established shivering. Pethidine has been shown to be one of the most effective treatments for shivering; however, it may cause respiratory depression, sedation, nausea, and vomiting .
Dexmedetomidine is a potent and highly selective α2-adrenoceptor agonist with sympatholytic, sedative, amnestic, and analgesic properties, which was previously described as a useful and safe adjunct in many clinical applications . Intravenous administration of this agent has been shown to effectively prevent postoperative shivering following spinal  and general anesthesia ; however, continuous intraoperative infusion of a medication could be cumbersome, in addition to the short duration of its action after holding the infusion. Therefore, the aim of this study was to compare the effect of dexmedetomidine administered by the intramuscular (i.m.) route with placebo for prevention of PAS in patients undergoing arthroscopic anterior cruciate ligament (ACL) reconstruction under general anesthesia.
| Materials and methods|| |
This prospective, randomized, and double-blind controlled study was conducted in King Abdulaziz Naval Base Hospital, Jubail, Kingdom of Saudi Arabia from August 2011 to December 2012. The protocol was approved by the Hospital Ethics Committee and written informed consent was obtained from each patient. We studied 85 patients with ASA physical status I who were aged 18-40 years (all are male patients) and scheduled for arthroscopic ACL reconstruction for isolated ACL rupture (either partial or complete) and instability after recreational sports injury. Patients were excluded if they had an initial core body temperature of greater than 37.5°C or less than 36.5°C or if they had a known allergy to any drug used in the study.
All patients had been fasting for 8 h before surgery and they were premedicated with lorazepam 2 mg orally on the evening of operation. In the operating theater, intraoperative vitals monitors [ECG, noninvasive mean blood pressure, and peripheral oxygen saturation (SpO 2 )] were applied. The vital data were recorded before induction of anesthesia and at regular intervals thereafter. The ambient temperature of the operating room was maintained between 19 and 20°C with constant humidity 70%. All irrigation and i.v. fluids were administered at room temperature. All patients received a venous cannula inserted into one of the veins of the dorsum of the hand, and i.v. fluid (lactated Ringer's solution) was started at a rate of 7 ml kg/h. Anesthesia was induced with propofol 2 mg/kg, fentanyl 1.5 μg/kg, and atracurium 0.5 mg/kg to facilitate tracheal intubation. The lungs were ventilated to maintain normocapnia [the end-tidal carbon dioxide pressure (ETCO 2 ) between 35 and 40 mmHg] with 1-2% sevoflurane in 60% nitrous oxide and 40% oxygen for maintenance of anesthesia. Supplemental boluses of atracurium 0.1 mg/kg were administrated as required to maintain muscle relaxation during surgery. Tympanic membrane temperature was measured immediately after induction of anesthesia and at regular intervals thereafter. A core body temperature below 36°C was considered hypothermia. The patients were covered with a warmed sheet and one layer of surgical drapes during the operation, then with a warmed cotton blanket postoperatively.
Patients were randomized using a computer-generated random list into one of the two groups before induction of anesthesia: the dexmedetomidine group (group D) and the control group (group C). Forty-five minutes before the expected end of surgery, the patient received an i.m. injection in the deltoid muscle of either dexmedetomidine 2.5 μg/kg (Precedex; Hospira Inc., Lake Forest, Illinois, USA) (group D, n = 43) or isotonic saline (group C, n = 42). Blinding was carried out by a technician, not involved in the data collection, who made up identical syringes of dexmedetomidine and 0.9% isotonic saline in equal volumes under sterile conditions.
After completion of surgery and application of surgical dressing, sevoflurane was discontinued and atropine 10 μg/kg and neostigmine 50 μg/kg were used to antagonize the residual neuromuscular block. The trachea was extubated after recovery of adequate spontaneous ventilation, and the extubation time (taken from cessation of sevoflurane inhalation) was noted. The time to eye opening to command (taken from cessation of the inhalational anesthetic) was also recorded. After surgery, the patients were transferred to the postanesthesia care unit (PACU) where they were monitored and received oxygen by face mask at 6 l/min. The temperature of PACU was maintained at 22-23°C with constant humidity. The presence of shivering (defined as readily detectable fasciculation or tremors of the face, limb, or trunk to a minimum of 15-s duration) was assessed by the PACU staff who were blinded to the treatment group, on admission to the PACU and at 5, 10, 15, 20, and 30 min thereafter. PAS was graded using a five-point scale:
0 = no shivering;
I = piloerection or peripheral cyanosis without visible muscle activity;
II = visible tremors involving one muscle group;
III = visible tremors involving more than one muscle group but not generalized;
IV = muscular activity involving the whole body.
For PAS grades III and IV, a rescue dose of pethidine 0.4 mg/kg i.v. was given. Time to onset of shivering (taken from tracheal extubation) and time to disappearance were noted. Recurrence of shivering was also noted.
The intensity of postoperative pain was assessed on admission to PACU, at second, fourth, sixth, 12th, and 24th postoperative hours, and each time the patient complained of pain, by nurses who were blinded to the treatment group using a 10-cm visual analog scale on which 0 cm indicated no pain and 10 cm the worst imaginable pain. Intravenous tramadol 1 mg/kg was administered when the visual analog scale was greater than 3 cm or upon patient's request. If pain scores remained greater than 3 for more than 30 min, lornoxicam 8 mg i.v. was used as a rescue analgesic. Total dose of the postoperative analgesic consumption of tramadol and the number of patients who needed rescue analgesic were recorded.
The degree of sedation was monitored and recorded on admission to PACU and at the second, fourth, sixth, and 12th postoperative hours, using a four-point scale:
0 = awake and alert;
1 = drowsy;
2 = mostly sleeping; and
3 = difficult or impossible to awake.
The presence of nausea and vomiting was noted throughout the first 6 h after surgery and was managed by giving an i.v. bolus of ondansetron 4 mg. Other side effects possibly related to dexmedetomidine, such as bradycardia and hypotension (heart rate and mean arterial pressure decreased >30% from baseline), respiratory depression (persistent respiratory rate <10/min), or desaturation (SpO 2 <92%), were recorded for each patient, and suitable treatment was given as clinically indicated.
The required sample size was calculated using IBM© SPSS© SamplePower© version 3.0.1 (IBM© Corp., Armonk, New York, USA). The primary outcome measure was the incidence of PAS. A previous study  reported that the incidence of PAS after orthopedic and abdominal surgeries was 55% in patients receiving no intervention to prevent PAS. Thus, it was estimated that a sample of 42 patients in each study group would have a power of 81% to detect an absolute reduction of 30% in the incidence of PAS in association with dexmedetomidine.
Statistical analysis was performed on a personal computer using IBM© SPSS© Statistics version 21 (IBM©© Corp.). The Kolmogorov-Smirnov goodness-of-fit test was used to test the normality of numerical data distribution. Normally distributed numerical data were presented as mean and SD and differences between the two groups were compared using the unpaired Student t-test. Categorical data were presented as number and percentage and differences between the two groups were compared using the Pearson c2 -test with Yates' correction or the c2 -test for trends for nominal or ordinal data, respectively. All P values are two-sided. P value less than 0.05 is considered statistically significant.
| Results|| |
All patients completed the study. There were no differences in patient characteristics between the two groups [Table 1]. There were no statistical differences in the preoperative baseline hemodynamic and respiratory parameters between the two groups. The mean ± SD extubation time was statistically significantly longer in the dexmedetomidine group than in the control group (8.4 ± 2.3 vs. 7.2 ± 2.6 min, respectively; P = 0.0268), but it was clinically insignificant. The mean ± SD time to eye opening to command was prolonged in group D (10.8 ± 4.0 min) than in the control group (8.8 ± 3.1 min; P = 0.0119).
There was a high incidence of hypothermia in this study, with no statistically significant difference between the two groups. Hypothermia was recorded in 19 patients in group D (44.1%) and 17 patients (40.4%) in the control group (P = 0.8993).
On admission to the PACU, 27 patients (64.28%) in the control group experienced PAS compared with only five patients (11.62%) in the dexmedetomidine group (P ≤ 0.0001), with lower intensity of shivering in group D than in the control group. Grades III or IV shivering were not observed in any patient receiving dexmedetomidine. The mean ± SD onset times of shivering did not differ significantly in the two groups (8.0 ± 1.9 min in group D vs. 7.3 ± 2.1 min in the control group; P = 0.1107). Details of PAS are given in [Table 2]. In the control group, PAS that required treatment disappeared 2-6 min after administration of i.v. pethidine, except in three patients in whom PAS disappeared after 25-30 min of pethidine administration (P = 0.026). All patients who shivered in the dexmedetomidine group, as well as the patients with shivering grades I and II in the control group responded well to a warm cotton blanket within 10-15 min, except two patients in group C who continued to have shivering grade II for almost 30 min (P = 0.489). Recurrence of shivering was not seen in any patient.
Pain intensity scores were significantly lower in the dexmedetomidine-treated patients until 2 h after operation (P = 0.0239) [Table 3]. The mean ± SD 24 h postoperative tramadol consumption was significantly higher in the control group than in the dexmedetomidine group (68.2 ± 12.0 vs. 61.9 ± 13.5 mg, respectively; P = 0.026). In addition, 31 patients in the control group (73.8%) required rescue analgesia during the first 24 h postoperatively compared with only 12 patients (27.9%) in group D (P ≤ 0.0001). The scores of sedation were significantly higher in group D than in group C until 4 h postoperatively (P<0.05). No patient had sedation score of 3 [Table 4]. Significantly more patients in the control group (30 patients) experienced nausea and vomiting during the first 6 h after surgery compared with nine patients in group D (P ≤ 0.0001).
Heart rates and mean arterial pressure were significantly lower in group D than in group C (P < 0.05) in most of the assessments until 6 h postoperatively, with the maximum decrease observed 1 and 2 h after surgery [Figure 1] and [Figure 2]. Nine patients in the dexmedetomidine group received atropine for bradycardia that occurred 17-55 min after surgery. No patient in the control group developed bradycardia (P = 0.005). A single patient in group D received ephedrine for hypotension. Hypotension was not recorded in the control group, but this was not statistically significant (P = 0.320). No other side effects related to the medications used in this study had been noticed.
| Discussion|| |
The results of this study showed that i.m. dexmedetomidine effectively decreased the incidence and severity of postoperative shivering following arthroscopic ACL reconstruction under general anesthesia. The incidence of PAS in the control group was 64.28%.
The development of shivering in patients undergoing surgery under general anesthesia could be due to intraoperative heat loss, sympathetic overactivity, postoperative pain, and systemic release of pyrogens . Volatile anesthetic agents decrease the normal cold-induced vasoconstriction, which promotes the development of hypothermia in the presence of a cold environment, and, despite the fact that most anesthetic medications also decrease the shivering threshold, PAS is commonly observed after emergence from general anesthesia . Postoperative shivering helps to increase the heat production and to raise the body temperature but could be associated with marked peripheral vasoconstriction. However, intense shivering can increase oxygen consumption (up to 400%)  with raised carbon dioxide production, hyperventilation, and increased cardiac output , in addition to arterial hypoxemia, lactic acidosis, increased intraocular and intracranial pressures, besides interfering with the postoperative hemodynamic monitoring . It should be noted that, in patients with pre-existing cardiac or pulmonary impairment, these physiological effect could be of extreme significance. In the present study, we observed a high incidence of hypothermia in both groups, which could be attributed to the low ambient temperature of the operating room that was maintained between 19 and 20°C according to the policy of our hospital with constant humidity 70%, in addition to the relatively long duration of surgery and the administration of all irrigations and i.v. fluids at room temperature. Therefore, the high incidence of PAS in the control group could be related to the increased incidence of hypothermia. In addition, grades III and IV shivering were frequently observed in group C which could be due to the nature of the sample population enrolled in the current study, as our patients were healthy adults, middle-aged men, and many of them were athletes with bulky muscles.
Previous studies have demonstrated the efficacy of i.v. dexmedetomidine infusion in the prevention of PAS following spinal  and general anesthesia . Usta et al.  investigated the effect of dexmedetomidine infusion on shivering during spinal anesthesia. They enrolled 60 patients scheduled for elective minor surgical operations under spinal anesthesia with hyperbaric bupivacaine. Dexmedetomidine i.v. bolus 1 μg/kg was given over 10 min just after intrathecal injection, followed by an infusion of 0.4 μg/kg/h until completion of skin closure. They found that dexmedetomidine infusion significantly reduced shivering associated with spinal anesthesia without any major adverse events. Bicer et al. , in a study involving 120 patients scheduled for elective abdominal or orthopedic surgery of about 1-3 h duration, evaluated the efficacy of dexmedetomidine compared with pethidine and placebo in preventing PAS. They came to the conclusion that intraoperative infusion of i.v. dexmedetomidine 1 μg/kg reduced PAS as did pethidine 0.5 mg/kg.
Although the exact mechanism by which dexmedetomidine decreases the incidence of PAS is not known, several possibilities are available. α2-Adrenergic agonists decrease the central thermosensitivity by suppressing the neuronal transmission, which is mediated by the increased potassium conductance through G-coupled proteins that results in hyperpolarization of the neurons . Dexmedetomidine couples in an inhibitory manner to the L-type calcium channels. Restriction of calcium entry into the nerve cells causes inhibition of neurotransmitter release with increased accumulation of calcium ions on the neuron's surface in the posterior hypothalamus, lowering the threshold of the heat gain units by stabilizing the cell membrane . In addition, it induces sedation and anxiolysis by receptors in the locus ceruleus and analgesia by receptors in the spinal cord, without significant respiratory depression . The responses of activation of these receptors should include decreased sympathetic tone, with sympatholytic blunting of the neuroendocrinal and hemodynamic stress responses to anesthesia and surgery . Therefore, dexmedetomidine can attenuate the undesirable effects of shivering, such as increased catecholamine concentrations, oxygen consumption, blood pressure, and heart rates, while avoiding vasoconstriction and increasing the level of shivering threshold, whereas meperidine only increases the shivering threshold .
The dose of dexmedetomidine used in the current study as well as the route of administration warrant discussion. Previous studies have reported that administration of large dose of dexmedetomidine as an i.v. bolus resulted in vasoconstriction accompanied by transient hypertension and bradycardia by activation of α2B -adrenoceptor in the vascular smooth muscles and inhibition of cardiac sympathetic drive . In addition, an i.v. bolus of dexmedetomidine has a limited duration of action and a continuous infusion, although effective, is cumbersome . Therefore, dexmedetomidine was administered by the i.m. route in this study to avoid the transient hypertension and bradycardia seen after an i.v. bolus and to prolong its duration of action. Of note, the i.m. route of dexmedetomidine administration has been described previously in the care of adults  and children  with bioavailability of 104% . To the best of our knowledge, no particular dose of i.m. dexmedetomidine for prevention of PAS is found in the medical literature; thus, we chose the i.m. dose of dexmedetomidine that was found to produce adequate preoperative sedation and anxiolysis ,. Almost the same i.m. dose of dexmedetomidine had been used by Mason et al.  to provide sedation in children undergoing computed tomography and MRI imaging.
As a result of using this 'sedative' i.m. dose of dexmedetomidine in the current study, the patients treated with this agent had a significantly delayed recovery from anesthesia compared with the control group. This was evident by the prolonged extubation time and prolonged time to eye opening to command. Besides, the measured sedation scores of these patients were significantly higher until 4 h postoperatively than in the control group. We observed the 'classical' pattern of dexmedetomidine sedation during the early postoperative period. The patients who received this medication were not deeply sedated; they appeared to be asleep but were easily aroused with verbal or physical stimuli. We believe that this pattern of sedation could be desirable after recovery from general anesthesia and throughout the early postoperative period. However, further studies are warranted to determine the optimum i.m. dose of dexmedetomidine for prevention of PAS in adults.
Several studies in the literature have demonstrated the analgesic and opioid-sparing effect of dexmedetomidine infusion in both children and adults. Ohtani et al. , in a study involving 32 patients undergoing open gynecological surgery under general anesthesia with postoperative patient-controlled epidural analgesia, reported that continuous dexmedetomidine infusion starting during induction of anesthesia resulted in antinociception without significant side effects. Onodera et al.  compared i.v. dexmedetomidine infusion with i.v. fentanyl infusion to provide postoperative analgesia following abdominal aortic surgery in patients with bleeding tendency or on anticoagulant therapy. They found that i.v. dexmedetomidine analgesia was safer with respect to respiratory depression and was more useful than i.v. fentanyl analgesia. Patel et al. , in a study involving 120 children with obstructive sleep apnea syndrome undergoing tonsillectomy and adenoidectomy, demonstrated that intraoperative infusion of dexmedetomidine 0.7 μg/kg combined with inhalational anesthetics provided satisfactory intraoperative conditions with significant reduction in postoperative opioids consumption. Solanki et al.  added dexmedetomidine 5 μg to intrathecal bupivacaine in a clinical trial involving 90 trauma patients scheduled for lower limb surgery under spinal anesthesia. They concluded that dexmedetomidine added to intrathecal bupivacaine resulted in prolonged postoperative analgesia and decreased the requirement for rescue analgesia during the first 24 h postoperatively. In agreement with these reports, analysis of the pain intensity scores in the present study revealed significantly lower values in the dexmedetomidine-treated patients until 2 h after operation than in the control group, with significant reduction in postoperative tramadol consumption and less requirement of postoperative rescue analgesia. We believe that a medication capable of reducing PAS and postoperative pain, together with providing a desirable level of postoperative sedation, could be of interest in the continuous trials to improve the overall postoperative patient satisfaction.
In this study, we observed mild hemodynamic side effects of dexmedetomidine. These observations are in accordance with previous reports evaluating the side effects of this agent. They have shown that the hypotensive effect of dexmedetomidine persists during the postoperative period , and the use of dexmedetomidine has not been associated with respiratory depression, despite profound level of sedation . In the present study, bradycardia and hypotension induced by dexmedetomidine remained within clinically accepted ranges and returned gradually to the baseline values without a rebound effect. In addition, when active management was needed, dexmedetomidine-induced bradycardia and hypotension were easily treatable by sympathomimetic drugs, which remain effective as α2 -agonists and do not block the adrenergic receptors . In contrast, postoperative nausea and vomiting were the prevalent side effects in the control group. This could be attributed to the frequent use of pethidine in the control group to treat PAS grades III and IV. Besides, a possible antiemetic effect of dexmedetomidine could have a role in decreasing the frequency of postoperative nausea and vomiting in patients receiving this agent .
A possible limitation of the current study could be the enrolled sample population, which consisted of middle-aged, ASA physical status I men. Therefore, it has to be determined whether our findings can be generalized to other age groups, female sex, and ASA physical status II and III patients.
| Conclusion|| |
This study demonstrated that i.m. dexmedetomidine 2.5 μg/kg provided effective prophylaxis against shivering after general anesthesia following arthroscopic ACL reconstruction without major side effects. Further studies are needed to determine the optimum i.m. dose of this agent for prevention of PAS in adult.
| Acknowledgements|| |
Conflicts of interest
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]